ukhcdo annual report 2018 & bleeding disorder statistics ......ukhcdo annual report 2018 &...

UKHCDO Annual Report 2018 & Bleeding Disorder Statistics for 2017/2018

Published by United Kingdom Haemophilia Centre Doctors’ Organisation 2018

© UKHCDO 2018

Copyright of the United Kingdom Haemophilia Centre Doctors’ Organisation. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any other form by any means, electronic, mechanical, photocopying or otherwise without the prior permission in writing of the Chairman, c/o Secretariat, UKHCDO, City View House, Union Street, Ardwick, Manchester, M12 4JD.

ISBN: 978-1-901787-22-1


Contents

1. Chairman’s Report 1

2. Bleeding Disorder Statistics for 2017 / 2018 Contents 6

2.0. Comments on the Bleeding Disorder Statistics for 2017 / 2018 12

2.1 Haemophilia A 15

2.2 Haemophilia B 45

2.3 Von Willebrand Disease 57

2.4 Inhibitors Congenital and Acquired 63

2.5 Rarer Bleeding Disorders 69

2.6 Adverse Events 74

2.7 Morbidity and Mortality 76

3. Haemtrack Report 2017 84

4. Data Management Working Party 93

5. Data Analysis Group 96

6. Co-Morbidities Working Party 98

7. Genetics Working Party 99

8. Genetic Laboratory Network 101

9. Inhibitor Working Party 103

10. Laboratory Working Party 105

11. Musculoskeletal Working Party 107

12. Paediatric Working Party 108

13. Von Willebrand Working Party 110

14. Peer Review Working Party 111

15. Gynaecology Task Force 112

16. Prophylaxis Task Force 113

17. Haemophilia Nurses’ Association 114

18. Haemophilia Chartered Physiotherapists' Association 116

19. BCSH Haemostasis and Thrombosis Task Force 118

20. Haemophilia Society 121

21. Macfarlane Trust 124


Page | 1

1. Chairman’s Report Welcome for the third time to the QEII Centre in London for the 2018 Annual General Meeting of the UKHCDO. The two previous AGMs have been very well attended compared to the preceding meetings held outside London and we thought a larger suite of rooms in this setting would be an ideal venue in which to celebrate the 50th anniversary of the foundation of the National Haemophilia Database. We have invited number of past and retired UKHCDO members to join us and some have accepted; we very much hope they enjoy the educational and social aspects of the meeting.

We have followed the same format as previous years with one or two small changes; we will have an educational day on the Thursday, aiming to cover many current topic issues of scientific and clinical interest. These sessions will be open to all members, our invited past members, guests, Sponsors and some trainees if numbers allow. The Friday sessions will start with an open presentation of the annual statistics and after morning coffee break we will have a business AGM, closed to Members and invited guests only.

The 3rd year of my current term as UKHCDO Chair has again been demanding and challenging but I continue to be supported by my close colleagues at Great Ormond Street Hospital Haemophilia Centre who shoulder the clinical burden and I am extremely grateful and lucky to have them as my team-mates.

When I wrote my report last year the announcement by the Prime Minister that there would be a Public Inquiry to investigate treatment-related infection of haemophiliacs and others in the 70’s-90’s was relatively recent news. We were still waiting to hear which Government department would lead the Inquiry and what the full remit would be. Twelve months on the process is underway; the terms of reference have been developed and published, the preliminary hearings have been heard and the Inquiry is onto the gathering evidence phase. The Inquiry team are making arrangements to visit the National Haemophilia Database where a large volume of archived material is held and they also wish to access relevant parts of the electronic database. The NHD is working with current haemophilia treaters to make sure that the data held is as comprehensive as possible and meanwhile all Trusts with Haemophilia Comprehensive Care and Treatment Centres have been asked by the Inquiry office to search for any relevant documentation at their hospitals that should be disclosed as evidence to the Inquiry Investigators. We are well aware that these current exercises are putting a real burden on our stretched Services but we know that as an Organisation we all recognise the devastating effect that these infections have had on patients and their families and we are all totally committed to helping the Inquiry reach a fully-informed conclusion.

At the same time as at looking back to the misery caused by the transfusion transmitted infections in our patients we have had an enormously exciting year in our treatment journey with a new product available to treat our most difficult patients – those with resistant inhibitors. Emicizumab or Hemlibra has been licensed and received NHS approval to be used and many patients and clinicians have already seen immense benefit with very significant reductions in bleed rate and considerable improvements in quality of life. The pathway to successful adoption of NHSE Policy is a convoluted one but we received unerring support from the Lead Commissioner for Haemophilia - Will Horsley – for both the Emicizumab and the other adopted Policy – the use of recombinant porcine factor VIII in the treatment of bleeding in acquired haemophilia. In the coming months we are going to be working on securing the use of Emicizumab for non-inhibitor patients with an additional Policy and we are hopeful that it is not


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too long before we will be doing the same for other novel treatments including additional new molecules and gene therapy for both haemophilia A and B.

Meanwhile our standard haemophilia A products went through a re-tender process in late 2017 which commenced in February 2018. It was a collaborative project between the UKHCDO and the NHS England Clinical Reference Group (CRG) for Haemophilia and, as with previous tenders, we benefitted from considerable expertise and support from Alison Greenwood and Wendy Roach from the NHSE Commercial Medicines Unit. The tender was highly successful in terms of the projected savings to be realised for the NHS; a number of patients had to switch products and we recognise the inconvenience to patients and the time invested by Centre staff in the administration required to switch patients to realise the savings. In 2018 we also tendered for all the other products that are not recombinant factor VIII and IX; modest savings were achieved here.

Over the last year we have seen progress in a number of UKHCDO initiatives and you will hear about a number of them during the AGM. The Data Analysis Group (DAG) is a sub-group of the Data Management Working Party and it meets by teleconference monthly. The main role of this Group is the assessment and prioritisation of requests for data from a number of sources, many of which generate income which supports the running of the NHD. We have completed reports requested by a number of commercial companies and abstracts and publications have resulted from several of these.

The Clinical Studies Group has been in existence for 2-3 years and has partnered with the James Lind Alliance to establish a Priority Setting Partnership on Bleeding Disorders with the aim of identifying the most important research areas going forwards. The James Lind Alliance runs the Partnership with well-established and validated methodology and brought together patients, carers and health and social care professionals to identify the important unknowns in diagnosis and treatment in the field of bleeding disorders. It has now completed its work and the three highest ranked research priorities in inherited bleeding disorders were: 1. How can we balance the risk and benefit of antithrombotic (blood thinning) treatment for cardiovascular disease (including heart attacks and strokes) in patients with bleeding disorders?; 2. How should heavy periods be managed in women with bleeding disorders?; 3. What are the most effective treatments for acute and chronic pain in people with haemophilia? The full list of the top 10 priorities can be found at http://www.jla.nihr.ac.uk/top-10-priorities/.

Last year during the AGM we introduced the format for the 2018/9 Peer Review process and I am delighted to say that our partnership with the West Midlands Quality Review Service has developed to the ‘almost-there’ stage and the 1st review using these high-quality robust standards will happen in the same month as the AGM. All reviews should be completed by AGM 2019 when we should aim to have a detailed discussion on how the results of the Peer Review can help to shape our Services going forward. I would like to thank John Hanley for his sterling efforts in Chairing the Peer Review Working Party and to the other members on the Group. We also had considerable support from nursing, physio and other colleagues and patient representatives and I would like to thank them for their help with this initiative and other UKHCDO work streams.

Finally, I would like to express my gratitude for the continuing support of the rest of the Executive Committee; Professor Peter Collins as Vice Chair; Dr Kate Talks as Secretary and Dr Pratima Chowdary as Treasurer. Both Pratima and I are up for re-election for a 2nd 3 year term; the outcome of this is not finalised at the time I am writing this report. On behalf of the Executive and all members I would also like to thank Professor Charlie Hay for his sustained


Page | 3

efforts in running and managing the National Haemophilia Database and all the other members of NHD staff including the statisticians for their hard work in supporting the UKHCDO. Special thanks go to Lynne Dewhurst for her ongoing hard work which has underpinned the continued achievements of the NHD. Lastly – and not at all least - is considerable personal gratitude to Sarah Rooney without whose support the role as UKHCDO Chair would not be remotely manageable.

Dr Ri Liesner, UKHCDO Chair

October 2018


Page | 4


Page | 5

Bleeding Disorder Statistics for April 2017 to March 2018

A report from the UK National Haemophilia Database

October 2018


Page | 6

2. Bleeding Disorder Statistics for 2017 / 2018 Contents

Appendix 1: Glossary ........................................................................................................................ 10

2.0. Comments on the Bleeding Disorder Statistics for 2017 / 2018 .............. 12

2.1 Haemophilia A ........................................................................................ 15

Table 1 Patients with congenital haemophilia A (including carriers) registered and

treated, 2017/018 ................................................................................................ 16

Figure 1 Carriers of haemophilia A currently registered and newly registered, by

baseline factor VIII level, 2017/18 ........................................................................ 17

Table 2 New registrations of haemophilia A (including carriers), by age at mid‐

year, gender and severity, 2017/18 ..................................................................... 18

Table 3 New registrations of patients with severe haemophilia A aged over 2 years

old, and subsequent treatment by year ............................................................... 19

Figure 2a Trend in the number of patients with severe haemophilia A aged 60 years

and above, 1977 – 2017/18 (including HIV +ve pts)............................................. 20

Figure 2b Trend in the number of patients with moderate haemophilia A aged 60

years and above, 1977 – 2017/18 (including HIV +ve pts) ................................... 21

Figure 2c Trend in the number of patients with mild haemophilia A aged 60 years

and above, 1977 – 2017/18 (including HIV +ve pts)............................................. 21

Figure 3 Factor VIII units issued by UK haemophilia centres to treat haemophilia A,

1993 – 2017/18 .................................................................................................... 22

Figure 4 Factor VIII units issued by UK haemophilia centres to treat severe

haemophilia A, 2012/13 ‐ 2017/18 ...................................................................... 23

Figure 5 Factor VIII units per kilogram issued to treat severe haemophilia A,

2012/13 ‐ 2017/18 ................................................................................................ 24

Table 4a Treatment intensity of patients with severe haemophilia A treated with

standard FVIII, with no inhibitor – 2012/13 ‐ 2017/18 ......................................... 25

Table 4b Treatment intensity of patients with severe haemophilia A treated with

enhanced half‐life FVIII, with no inhibitor – 2015/16 ‐ 2017/18 .......................... 26

Table 5a Treatment intensity of patients with moderate haemophilia A treated

with standard FVIII, with no inhibitor – 2012/13 ‐ 2017/18 ................................ 27

Table 5b Treatment intensity of patients with moderate haemophilia A treated

with enhanced half‐life FVIII, with no inhibitor – 2016/17 ‐ 2017/18 .................. 28

Figure 6 Median usage of factor VIII: UK patients with severe haemophilia A

without inhibitors broken down by age, 2012/13 – 2017/18 .............................. 29

Figure 7 Patients with severe / moderate / mild haemophilia A treated with FVIII

by UK haemophilia centres – 2009/10 – 2017/18 ................................................ 30

Table 6 Factor VIII usage by region for patients with severe haemophilia A (incl.

treatment for inhibitors and EHL‐VIII), 2017/18 .................................................. 31

Figure 8a Annual FVIII usage (IU/Kg/Pt) in patients with severe haemophilia A aged

under 18 years with no current inhibitor, by centre, ranked by median

usage ..................................................................................................................... 32


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Figure 8b Annual FVIII usage (IU/Pt) in patients with severe haemophilia A aged

under 18 years with no current inhibitor, by centre, ranked by median

usage per patient .................................................................................................. 34

Figure 9a Annual FVIII usage (IU/Kg/Pt) in patients with severe haemophilia A aged

18 years or more with no current inhibitor, by centre, ranked by median

usage ..................................................................................................................... 35

Figure 9b Annual FVIII usage (IU/Pt) in patients with severe haemophilia A aged 18

years or more with no current inhibitor, by centre, ranked by median

usage per patient .................................................................................................. 37

Figure 10 Median factor VIII units issued per kilogram body weight per year in

patients with severe haemophilia A without inhibitors by age ........................... 38

Figure 11 Median factor VIII units issued (IU/kg) in patients with severe haemophilia

A without inhibitors aged 16 and over, by bodyweight ....................................... 39

Figure 12 Patients with severe haemophilia A with no current inhibitor in the

reporting year: median usage by inhibitor history ............................................... 40

Table 7 Products issued to treat haemophilia A (including inhibitors), 2017/18 ............. 41

Table 8 Factor VIII units issued by UK haemophilia centres, by diagnosis. 2017/18 ........ 43

Figure 13 Market Share of factor VIII concentrates issued by UK haemophilia

centres, 2017/18 .................................................................................................. 44

2.2 Haemophilia B ........................................................................................ 45

Table 9 Patients with congenital haemophilia B (including carriers) registered and

treated, 2017/18 .................................................................................................. 46

Figure 14 Carriers of haemophilia B currently registered and newly registered, by

baseline factor IX level, 2017/18 .......................................................................... 47

Table 10 New registrations of haemophilia B (including carriers), by age at mid‐

year, gender and severity, 2017/18 ..................................................................... 48

Figure 15a Trend in numbers of severe haemophilia B patients aged 60 years and

above, 1977 – 2017/18 (including HIV +ve pts).................................................... 49

Figure 15b Trend in numbers of moderate haemophilia B patients aged 60 years and


Figure 15c Trend in numbers of mild haemophilia B patients aged 60 years and


Figure 16 Factor IX units issued by UK haemophilia centres to treat haemophilia B,

1993 – 2017/18 .................................................................................................... 51

Table 11 Factor IX usage by region for patients with severe haemophilia B (incl.

treatment for inhibitors and EHL‐IX), 2017/18 .................................................... 52

Table 12 Products issued to treat haemophilia B (including inhibitors), 2017/18 ............. 54

Table 13 Factor IX units issued by UK haemophilia centres, by diagnosis, 2017/18 .......... 55

Figure 17 Market Share of factor IX concentrates issued by UK haemophilia centres,

2017/18 ................................................................................................................ 56


Page | 8

2.3 Von Willebrand Disease ......................................................................... 57

Table 14 Patients with von Willebrand disease registered and treated April 2017 ‐

March 2018 ........................................................................................................... 58

Table 15 New Registrations of von Willebrand disease between April 2017 & March

2018, by age at mid‐year, severity, and gender ................................................... 60

Figure 18 Factor VIII units issued by UK haemophilia centres to treat Von Willebrand

disease 1993 – 2017/18 ........................................................................................ 61

Table 16 Products issued to treat von Willebrand disease (including inhibitors),

2017/18 ................................................................................................................ 62

2.4 Inhibitors: Congenital and Acquired ........................................................ 63

Table 17 Inhibitors by disease severity – haemophilia A, haemophilia B & von

Willebrand disease ............................................................................................... 64

Table 18 Products issued to patients with congenital bleeding disorders reported

to have a positive inhibitor during 2017/18 ......................................................... 66

Table 19 Products issued to patients with Acquired Inhibitors 2017/18 ............................ 67

Table 20 FEIBA® usage: breakdown by diagnosis ................................................................ 68

Table 21 NovoSeven® usage: breakdown by diagnosis ....................................................... 68

2.5 Rarer Bleeding Disorders ....................................................................... 69

Table 22 Patients with rarer types of bleeding disorders registered and treated

April 2017 & March 2018 ..................................................................................... 70

Table 23 Patients with selected rarer bleeding disorders registered and treated

April 2017 – March 2018, by disease severity ...................................................... 71

Table 24 New registrations of rarer bleeding disorders between April 2017 &

March 2018 showing their coagulation defect and gender ................................. 72

Table 25 Concentrates used to treat rarer bleeding disorders between April 2017

& March 2018 ....................................................................................................... 73

2.6 Adverse Events ...................................................................................... 74

Table 26 Adverse Events reported between April 2017 & March 2018 ............................. 75

2.7 Morbidity and Mortality ........................................................................... 76

Table 27 Causes of death in patients with haemophilia A and B between April 2017

& March 2018 ....................................................................................................... 77

Table 28 Causes of death in other coagulation defects between April 2017 & March

2018 ...................................................................................................................... 78

Figure 19 Cumulative incidence chart of deaths from hepatocellular carcinoma or

liver failure in UK patients with bleeding disorders 1969 ‐ 2017 ......................... 79

Table 29 Summary of patients ‘at risk’ of vCJD for public health purposes who

received UK sourced plasma products as reported by centres ............................ 81

Figure 20 Total number of patients with haemophilia A, haemophilia B or von

Willebrand disease treated by UK haemophilia centres ...................................... 82


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Figure 21 Total number of patients with severe haemophilia A and haemophilia B

treated by UK haemophilia centres ...................................................................... 82

Appendix 2: Participating Centres .................................................................................................... 83

3. Haemtrack Annual Report 2017 ............................................................. 84

Introduction 84

Section 1: Patients’ Haemtrack Usage Analysis 85

Figure 1 Number of patients using Haemtrack and recruitment rate, 2008-2017 85

Figure 2 Comparison of recruitment to Haemtrack by centre for patients with severe haemophilia A: Comprehensive Care Centres (CCCs) in 2017 87

Figure 3 Comparison of recruitment to Haemtrack by centre for patients with severe haemophilia A: Haemophilia Centres (HCs) in 2017 87

Figure 4 Overall compliance in patients with severe haemophilia A, by Comprehensive Care Centre 88

Figure 5 Overall compliance in patients with severe haemophilia A, by Haemophilia Centre 89

Section 2: Patients’ Reporting Analysis 90

Figure 6 Change in the use of different Haemtrack Reporting Media: 2011- 2017 90

Figure 7 Haemtrack Reporting Delay by Reporting Medium 2017 91

Figure 8 Reporting compliance by reporting medium, ranked by median compliance 2017 (CCC’s) in patients with severe haemophilia A 92


Page | 10

Appendix 1: Glossary

BCSH British Committee for Standards in Haematology

BMI Body mass index

BMS Biomedical Scientist

BPG Best practice guideline

BSA Business Services Authority

BSH British Society for Haematology

CCC Comprehensive Care Centre

CMWP Co-morbidities Working Party

CQUIN Commissioning for Quality and Innovation

DAG Data Analysis Group

DH Department of Health

DMWP Data Management Working Party

EAHAD European Association for Haemophilia and Allied Disorders

ECH European Haemophilia Consortium

EHL Enhanced Half-life

EQA External quality assessment

EU European Union

FVIII Factor VIII

FIX Factor IX

GLN Genetic Laboratory Network

GWP Genetics Working Party

HC Haemophilia Centre

HCC Hepatocellular carcinoma

HCIS Haemophilia Clinical Information System

HCPA Haemophilia Chartered Physiotherapists’ Association

HCV Hepatitis C virus

HEAD-US Hemophilic Early Arthropathy Detection with UltraSound

HIV Human immunodeficiency virus

HJHS Haemophilia Joint Health Score

HNA Haemophilia Nursing Association

ICF International Classification of Function

ICH Intracranial haemorrhage


Page | 11

IQR Interquartile range

ISO International Organization for Standardization

ITI Immune tolerance induction

IU/dl International units per decilitre

IU/kg International units per kilogram

IWP Inhibitor Working Party

kg Kilogram

MDSAS Medical Data Solutions and Services

MFT The Macfarlane Trust

MSK Musculoskeletal

NEQAS National External Quality Assessment Service

NGS Next generation sequencing

NHD National Haemophilia Database

NHS National Health Service

NHSE NHS England

NIBSC National Institute for Biological Standards and Control

NIHR National Institute for Health Research

PSWD Pulsed shortwave diathermy

PUP Previously untreated patient

PWP Paediatric Working Party

RCOG Royal College of Obstetricians and Gynaecologists

SHL Standard Half-life

TTP Thrombotic thrombocytopenic purpura

TUPE Transfer of Undertakings (Protection of Employment) regulations

UK United Kingdom

UKAS United Kingdom Accreditation Service

UKGTN United Kingdom Genetic Testing Network

UKHCDO United Kingdom Haemophilia Centre Doctors’ Organisation

UKHCDO GLN United Kingdom Genetic Laboratory Network

VWD Von Willebrand disease

VWF Von Willebrand factor

WAPPS-Hemo Web-Accessible Population Pharmacokinetic Service—Hemophilia

WFH World Federation of Hemophilia

WMQRS West Midlands Quality Review Service


Page | 12

2.0. Comments on the Bleeding Disorder Statistics for 2017 / 2018

The following report details the registration, treatment and mortality statistics for the UK for the year 2017/18. Most of the commentary appears next to the table or figure to which it relates.

Increasingly, this report, focussing as it does on registrations, mortality and adverse events, does not fully reflect the range of activities undertaken by the database in its 50th year. Supplementary reports have been provided for Scotland and Wales. Many supplementary reports have been provided to NHS England and to the Suppliers, particularly those detailing changes in factor VIII/IX usage and annual bleed-rate (ABR) in patients switched to EHL-VIII and EHL-IX. These reports are being made available to be viewed by UKHCDO Members on a secure UKHCDO SharePoint site (not for wider dissemination). Data is also being collected on joint scoring and we would expect to report on this in the future.

Since April 2017 all new proposals and data requests have been reviewed or vetted by the Data Analysis Group (DAG), a subgroup of the Data Management Working Party. This group, which meets monthly by teleconference, is co-chaired by CRM Hay and PW Collins and includes two patient representatives, two statisticians and several working party chairs.

The database also supports a number of other projects, including a reassessment of mortality and life expectancy in patients with haemophilia and an assessment of the current hepatitis C status of patients currently registered.

In addition, UKHCDO and the National Haemophilia Database are cooperating fully with the Infected Blood Inquiry, giving the Inquiry open access to the electronic and paper archive going back 50 years.

Adverse events are listed in this report but are not presented in any detail. Whilst this is not entirely satisfactory, when we reported adverse events in more detail last year concerns were raised in relation to the potential identifiability of individuals and so we felt obliged to revert to the rather uninformative previous format. Adverse events thought to be product-related are reported to the supplier so that they may fulfil their regulatory obligation to investigate adverse events further.

Reports of causes of death continue to be a problem. NHS Digital ceased sending us death certification data about two years ago. We know which of our registered patients have died from the NHS Spine but rely on haemophilia centres to provide the cause of death, which they are unable to do in about a third of cases. We should be grateful if centres could report a higher proportion of causes of death to the database. Centres may not know the cause of death if the patient dies at home or in a different hospital from the reporting haemophilia centre.

It is our aim to renew our contract with NHS Digital to obtain death certification data, but this will depend on the Database being recognised as a Research Database (ethics application submitted) and changing from our current system of implied consent with an opt-out to a system of explicit written consent which will be introduced later this year. We anticipate that consent will have to be obtained face-to face on an opportunist basis with most consents being obtained from patients with severe haemophilia in the first 12 months. This will be a large task, which will require engagement and commitment from centres to ensure a high-level of consent.


Page | 13

Pharmacovigilance is an increasingly important aspect of the work of the database. The database has conducted and published several post-marketing studies, some mandated by the European Medicines Agency (EMA) and including two PUP studies. Over recent years we have forged an increasingly close working relationship with EMA and representatives of UKHCDO have met with EMA and participated in EMA Workshops on a regular basis. EMA have recently proposed to abandon pre-licensure PUP studies and to rely far more heavily on the real-world data produced by databases for the safety and efficacy data that they require. This is an initiative across the whole of the rare diseases therapeutic area, acknowledging the difficulty that fully powered drug trials are impractical in rare diseases. EMA anticipate that databases will have to collaborate to establish common datasets and potentially to aggregate anonymised data. Funding for this would presumably be obtained from Industry. This proposal is not without its problems not least of which is that databases can only report on the products prescribed by their reporting centres.

It is anticipated that we will shortly embark on the largest such study to date, documenting safety and relative efficacy of Emicizumab (Hemlibra®, Roche) as it is introduced for the treatment of patients with haemophilia A and inhibitors and subsequently for non-inhibitor patients. This is an enormous paradigm shift in the treatment of haemophilia A and it is important that we document outcome and safety, firstly of conventional treatment for within-patient comparison with Hemlibra, once patients have switched.

We would like to thank all Centre Directors and haemophilia centre staff for their hard work in sending us all this data over the past year and for their forbearance in the face of increasing demands. It is very much appreciated.

Professor Charles RM Hay,

Lynne Dewhurst, Ben Palmer & Dr Hua Xiang

On behalf of the UK National Haemophilia Database Manchester, October 2018


Page | 14

Important Note: Throughout this report, haemophilia A includes carriers of haemophilia A and females with FVIII deficiency.

Haemophilia B includes carriers of haemophilia B, females with FIX deficiency, patients with FIX Leyden and FIX Leyden carriers.

Time Periods: Unless otherwise stated, the tables and figures presented in this report relate to the period April 2017 – March 2018 inclusive.


Page | 15

2.1 Haemophilia A

Tab

le 1

P

atie

nts

with

con

geni

tal h

aem

ophi

lia A

(in

clud

ing

carr

iers

) re

gist

ered

and

trea

ted,

201

7/01

8

MF

Total

MF

Total

MF

Total

MF

Total

MF

Total

MF

Total

<18 years

702 ‐

702 194 5 199 591 105 696 28 158 186 ‐ 8

8

1,515 276 1,791

≥18 years

1,310 2 1,312 617 2 619 2,515 582 3,097 161 1,116

1,277 3

60

63

4,606 1,762

6,368

Total

2,012 2

2,014 811 7

818 3,106 687

3,793 189 1,274

1,463 3 68

7

1 6,121 2,038

8,159

<18 years

46 ‐

46

15 1

16

52 20

72

4

36

40

‐ 3

3

117 60 177

≥18 years

18 1

19

10 ‐

10

55 22

77

4

86

90

1

8

9

88 117 205

Total

6

4 1 6

5 2

5 1 2

6 107 42

149 8 122

130 1 11

1

2 205 177

382

<18 years

683 ‐

683 147 4 151 170 10 180 4

2

6

1

‐

1

1,005 16 1,021

≥18 years

1,261 ‐

1,261 403 2 405 636 44 680 15 27

42

‐ ‐

‐

2,315 73 2,388

Total

1,944 ‐

1,944 550 6

556 806 5

4 860 1

9 2

9 4

8 1 ‐

1 3,320 89

3,409

<18 years

665 ‐

665 144 4 148 148 5 153 3

2

5

1

‐

1

961 11 972

≥18 years

1,211 ‐

1,211 380 2 382 535 25 560 10 17

27

‐ ‐

‐

2,136 44 2,180

Total

1,876 ‐

1,876 524 6

530 683 3

0 713 1

3 1

9 3

2 1 ‐

1 3,097 55

3,152

Num

ber o

f Patients (Factor VIII le

vel (IU/dl))

< 1

1 ‐ 5

>5 & <40

≥ 40

Unk

nown

Total

Treated with

concentrate in

year**

Hae

mop

hilia

A

Age

Ra

nge

Total In Register

New Registrations *

Treated in

year**

*

New

regi

stra

tions

are

a s

ubse

t of t

he ‘I

n R

egis

ter’

num

bers

**

Tre

ated

incl

udes

pat

ient

s ‘In

Reg

iste

r’ an

d ‘N

ew R

egis

trat

ions

’

Tabl

e 1

show

s th

e to

tal n

umbe

r of

pat

ient

s w

ith h

aem

ophi

lia A

(in

clud

ing

carr

iers

and

def

icie

nt fe

mal

es)

regi

ster

ed in

the

UK

dur

ing

2017

/18

brok

en d

own

by a

ge a

nd d

isea

se s

ever

ity.

Page | 16



Page | 17

Figure 1 Carriers of haemophilia A currently registered and newly registered, by baseline factor VIII level, 2017/18

0

100

200

300

400

500

600

700

800

<2 2‐9 10‐19 20‐29 30‐39 40‐49 50+ N/K

2 13

68

205

364395

776

381 1 3 12 27

5276

5

Patie

nts (n)

Factor FVIII level (IU/dl)

Haemophilia A CarrierIn Register

(Excl. new registrations)

Haemophilia A CarrierNew Registrations

N.B: Includes carriers of haemophilia A and females with FVIII deficiency

<2 2‐9 10‐19 20‐29 30‐39 40‐49 50+ N/KGrand Total

Haemophilia A Carrier

In Register

(Excl. new registrations)

2 13 68 205 364 395 776 38 1,861

Haemophilia A Carrier

New Registrations1 1 3 12 27 52 76 5 177

Total 3 14 71 217 391 447 852 43 2,038

Diagnosis Number of Patients (Factor VIII level (IU/dl))

Figure 1 shows the number of carriers of haemophilia A currently registered with the NHD by baseline factor VIII level. This includes females registered by their centre as having factor VIII deficiency or haemophilia A. New registrations of unaffected carriers continue but are not yet complete. Very low levels amongst carriers are perhaps not quite as rare as might have been expected. Although this is usually accounted for by extreme lyonisation, two patients with levels <2 IU/dl are compound heterozygotes for mutations which cause severe haemophilia.

Tab

le 2

N

ew r

egis

trat

ions

of h

aem

ophi

lia A

(in

clud

ing

carr

iers

), b

y ag

e at

mid

-yea

r, g

ende

r an

d se

verit

y, 2

017/

18

Hae

mop

hilia

A MF

Total

MF

Total

MF

Total

MF

Total

MF

Total

MF

Total

0 ‐ < 2

38

‐

38

12

‐

12

23

5

28

2

4

6

‐

‐

‐

75

9

84

2 : 4

5

‐

5

1

‐

1

8

1

9

1

3

4

‐

‐

‐

15

4

19

5 : 9

‐

‐

‐

2

‐

2

9

9

18

1

10

11

‐

1

1

12

20

32

10 : 19

8

‐

8

2

1

3

14

8

22

‐

22

22

‐

3

3

24

34

58

20 : 29

8

‐

8

3

‐

3

6

8

14

2

23

25

1

1

2

20

32

52

30 : 39

4

1

5

3

‐

3

13

4

17

‐

29

29

‐

3

3

20

37

57

40 : 49

‐

‐

‐

1

‐

1

8

4

12

‐

10

10

‐

1

1

9

15

24

50 : 59

‐

‐

‐

1

‐

1

5

3

8

‐

9

9

‐

2

2

6

14

20

60 : 69

1

‐

1

‐

‐

‐

11

‐

11

‐

8

8

‐

‐

‐

12

8

20

70 +

‐

‐

‐

‐

‐

‐

10

‐

10

2

4

6

‐

‐

‐

12

4

16

Total

641

6525

126

107

42149

8122

130

111

12205

177

382

Num

ber o


vel (IU/dl))

Age

(yea

rs)

> 5 & < 40

≥ 40

Unk

nown

1 ‐ 5

< 1

Total

Tabl

e 2:

Thi

s sh

ows

the

num

ber

of n

ew r

egis

trat

ions

of h

aem

ophi

lia A

bro

ken

dow

n by

rep

orte

d se

verit

y an

d ag

e at

mid

-yea

r (3

0/09

/201

7).

The

und

erly

ing

birt

h ra

te o

f pat

ient

s w

ith s

ever

e ha

emop

hilia

A b

orn

in th

e U

K r

uns

at 4

0-45

pat

ient

s pe

r ye

ar.

Ove

r 40

% o

f new

reg

istr

atio

ns

of s

ever

e ha

emop

hilia

A w

ere

regi

ster

ed a

ged

two

year

s or

abo

ve.

All

of t

hese

pat

ient

s ar

e re

cent

mig

rant

s to

thi

s co

untr

y.

Just

und

er h

alf

of th

ese

patie

nts

com

e fr

om th

e w

ider

EU

, som

e of

who

m s

tay

for

only

a fe

w m

onth

s to

a y

ear

or s

o. T

he r

emai

nder

orig

inat

e fr

om th

e re

st o

f th

e w

orld

. T

his

appe

ars

to b

e a

stab

le tr

end

over

rec

ent y

ears

(se

e ta

ble

3).

Page | 18


Tab

le 3

N

ew r

egis

trat

ions

of p

atie

nts

with

sev

ere

haem

ophi

lia A

age

d ov

er 2

yea

rs o

ld, a

nd s

ubse

quen

t tre

atm

ent b

y ye

ar

Haem

ophilia

A2008/09

2009/10

2010/11

2011/12

2012/13

2013/14

2014/15

2015/16

2016/17

2017/18

New

registratio

ns / ye

ar18

1413

1812

2322

2723

22170

2008/09

181

19

2009/10

1710

27

2010/11

1611

1239

2011/12

1511

1117

54

2012/13

1311

917

1161

2013/14

1410

1015

1122

82

2014/15

1310

1015

1122

21102

2015/16

1311

813

1121

2126

124

2016/17

1210

713

1121

1922

232

140

2017/18

1210

710

1020

1918

2319

148

No treatment records

01

10

10

00

03

6

Total

2008/2018

Reg

istration ye

ar

Trea

ted in each ye

ar

Tabl

e 3:

T

his

show

s th

e nu

mbe

r of

pat

ient

s ov

er t

wo

year

s of

age

and

new

ly r

egis

tere

d (a

nd t

here

fore

tho

ught

to

be m

igra

nts)

eac

h ye

ar

from

200

8/09

. It

also

sho

ws

the

num

ber

trea

ted

in e

ach

year

sub

sequ

ent t

o th

eir

regi

stra

tion.

Thi

s sh

ows

that

pot

entia

lly a

t lea

st 1

70 p

atie

nts

with

sev

ere

haem

ophi

lia A

hav

e m

igra

ted

to t

he U

K s

ince

200

8/09

. T

his

is li

kely

to

be a

n un

dere

stim

ate,

sin

ce c

hild

ren

two

year

s ol

d an

d un

der

are

not i

nclu

ded

in th

is ta

ble.

Alth

ough

six

pat

ient

s in

the

tabl

e re

quire

d no

trea

tmen

t, 14

8 of

them

wer

e tr

eate

d in

201

7/18

, sug

gest

ing

that

mos

t rem

ain

and

requ

ire r

egul

ar tr

eatm

ent.

Page | 19



Page | 20

Figure 2a Trend in the number of patients with severe haemophilia A aged 60 years and above, 1977 – 2017/18 (including HIV +ve pts)

N.B. Carriers included in figures 2a – 2c

Figure 2a shows a more than doubling in the number of patients with severe haemophilia aged 60-74, and in those aged 75 and above, over the past forty years. The number of elderly patients with severe haemophilia A actually declined during the 1990’s because of deaths from HIV and HCV, recovering subsequently, as treatment improved.

Figure 2b (overleaf) The effect of HIV is not seen as markedly in moderate severity haemophilia A because proportionately fewer of these patients were infected. The number of patients aged greater than 60 years increased three-fold over the past 40 years. Some of this increase is probably attributable to better diagnosis rather than increasing lifespan.

Figure 2c (overleaf) shows the age trend for mild haemophilia A. This is difficult to interpret since the increased number may reflect increased diagnosis rather than just increased life expectancy.

02

04

06

08

01

00

60-74 75+ 60-74 75+ 60-74 75+ 60-74 75+ 60-74 75+

1977 1987 1997 2007 2017/18

Pa

tien

ts (

n)

Age group (years) by reporting yearGraphs by year


Page | 21

Figure 2b Trend in the number of patients with moderate haemophilia A aged 60 years and above, 1977 – 2017/18 (including HIV +ve pts)

Figure 2c Trend in the number of patients with mild haemophilia A aged 60 years and above, 1977 – 2017/18 (including HIV +ve pts)

02

04

06

08

01

00

60-74 75+ 60-74 75+ 60-74 75+ 60-74 75+ 60-74 75+

1977 1987 1997 2007 2017/18

Pa

tien

ts (

n)


01

002

003

004

005

006

00

60-74 75+ 60-74 75+ 60-74 75+ 60-74 75+ 60-74 75+

1977 1987 1997 2007 2017/18

Pa

tien

ts (

n)


0500

1,00

0

1,50

0

2,00

0

2,50

0

3,00

0

3,50

0

0

100

200

300

400

500

600

Pa�ents (n)

Units(millions)

Tim

e Pe

riod

Plas

ma

Reco

mbi

nant

Inve

s�ga�o

nal

EHL

Pa�e

nts t

reat

ed

Figu

re 3

Fa

ctor

VIII

uni

ts is

sued

by

UK

hae

mop

hilia

cen

tres

to tr

eat h

aem

ophi

lia A

, 199

3 – 2

017/

18

N.B

: Dat

a fo

r St T

hom

as’ w

ere

not s

ubm

itted

199

6-20

06.

Figu

re 3

sho

ws

UK

fact

or V

III u

nits

issu

ed to

trea

t hae

mop

hilia

A b

etw

een

1993

to 2

017/

18.

The

num

ber o

f pat

ient

s re

porte

d to

hav

e be

en

treat

ed is

sho

wn

by th

e bl

ue li

ne u

sing

a s

econ

dary

axi

s. T

his

show

s pa

tient

num

bers

hav

e in

crea

sed

by o

ver 4

0% d

urin

g th

is ti

me

whe

reas

fa

ctor

VIII

usa

ge h

ad m

ore

than

qua

drup

led.


| egaP 22

Fig

ure

4 F

acto

r V

III u

nits

issu

ed b

y U

K h

aem

ophi

lia c

entr

es to

trea

t sev

ere

haem

ophi

lia A

, 201

2/13

- 2

017/

18

IU (000

)

% differen

cesince

201

2/13

IU(000)

% differen

cesince

201

2/13

IU(000)

% differen

cesince

201

2/13

IU(000)

% differen

cesince

201

5/16

IU(000)

% differen

cesince

201

2/13

n

% differen

cesince

201

2/13

2012/13

34,072

100.00

344,322

100.00

7,871

100.00

0386,266

100.00

1,638

100.00

2013/14

30,780

90.34

364,514

105.86

18,462

234.55

0413,756

107.12

1,701

103.85

2014/15

32,932

96.65

395,614

114.90

17,476

222.02

0446,022

115.47

1,746

106.59

2015/16

32,081

94.15

419,302

121.78

14,317

181.89

285

100.00

465,985

120.64

1,793

109.46

2016/17

28,176

82.70

430,835

125.13

9,740

123.75

12,986

4552.61

481,738

124.72

1,833

111.90

2017/18

21,791

63.96

402,194

116.81

5,715

72.60

60,380

21167.33

490,080

126.88

1,876

114.53

Patie

nts T

reated

Year

Plasma

Recombina

nt

(excluding inve

stigational)

Inve

stigationa

l rFV

IIITo

tal

Enha

nced

Half‐L

ife FV

III

Figu

re 4

sho

ws

a ba

r di

agra

m o

f fa

ctor

VIII

usa

ge f

or

seve

re

haem

ophi

lia

A

in

the

UK

fr

om

2012

/13

to

2017

/18

(incl

udin

g in

hibi

tors

).

The

num

ber

of p

atie

nts

repo

rted

to h

ave

been

trea

ted

is s

how

n by

the

blue

line

us

ing

a se

cond

ary

axis

. T

his

show

s a

14.5

% in

crea

se

in

patie

nt

num

bers

ov

er

that

pe

riod

but

a 26

.9%

in

crea

se i

n pr

oduc

t us

e.

Thi

s ha

s se

en f

acto

r V

III

cons

umpt

ion

for

seve

re h

aem

ophi

lia A

inc

reas

e fr

om

386

mill

ion

units

in

2012

/13

to 4

90 m

illio

n un

its i

n 20

17/1

8.

Thi

s in

crea

se in

usa

ge is

larg

ely

attr

ibut

able

to

in

crea

sed

num

bers

of

pa

tient

s an

d in

crea

sed

indi

vidu

al

body

wei

ght

but

also

in

tens

ifica

tion

of

prop

hyla

xis.

N

ote

that

thi

s gr

aph

and

tabl

e in

clud

e pa

tient

s w

ith i

nhib

itors

and

are

the

refo

re n

ot d

irect

ly

com

para

ble

with

tabl

e 4a

.

Dat

a ta

ble

for f

igur

e 4


Page | 23

1,500

1,550

1,600

1,650

1,700

1,750

1,800

1,850

1,900

0

100

200

300

400

500

600

2012

/13

2013

/14

2014

/15

2015

/16

2016

/17

2017

/18

Patients (n)

Units(millions)

Time Pe

riod

Plasm

aReco

mbinant

Inve

stigational

EHL

Patients Treated

Fig

ure

5 F

acto

r V

III u

nits

per

kilo

gram

issu

ed to

trea

t sev

ere

haem

ophi

lia A

, 201

2/13

- 2

017/

18

Fig

ure

5 sh

ows

a ba

r di

agra

m o

f fac

tor

VIII

usa

ge in

IU/k

g fo

r pa

tient

s w

ith s

ever

e ha

emop

hilia

A.

Thi

s ta

ble/

diag

ram

is

not

dire

ctly

com

para

ble

with

the

pre

viou

s ta

ble.

T

his

show

s th

at,

sinc

e 20

12/1

3 th

e nu

mbe

r of

pat

ient

s w

ith

repo

rted

w

eigh

t ha

s in

crea

sed

by

10.6

%,

and

now

co

mpr

ises

82

.6%

of

F

VIII

-tre

ated

pa

tient

s w

ith

seve

re

haem

ophi

lia A

. M

edia

n us

age/

Kg

has

rem

aine

d al

mos

t un

chan

ged

durin

g th

is

perio

d,

impl

ying

th

at

trea

tmen

t in

tens

ity

(per

kg

) is

re

lativ

ely

stab

le.

T

he

med

ian

body

wei

ght

of p

atie

nts

with

hae

mop

hilia

A i

ncre

ased

by

1.4%

dur

ing

the

perio

d 20

12/1

3-20

17/1

8.

Incr

ease

d fa

ctor

VIII

usa

ge p

er-p

atie

nt i

s th

eref

ore

only

pa

rtly

attr

ibut

able

to

incr

ease

d bo

dyw

eigh

t. I

ncre

ased

ov

eral

l us

age

is l

arge

ly a

ttrib

utab

le t

o in

crea

sed

patie

nt

num

bers

.

Dat

a ta

ble

for f

igur

e 5

Page | 24


Med

ian

IU/Kg

% differen

cesince

201

2/13

Med

ian

IU/Kg

% differen

cesince

201

2/13

Med

ian

IU/Kg

% differen

cesince

201

2/13

Med

ian

IU/Kg

% differen

cesince

201

5/16

Med

ian

IU/Kg

% differen

cesince

201

2/13

n% differen

cesince

201

2/13

2012/13

5,939

100.00

3,527

100.00

2,780

100.00

3,638

100.00

1,400

100.00

2013/14

5,809

97.81

3,616

102.52

3,886

139.78

3,799

104.43

1,643

117.36

2014/15

6,301

106.10

3,790

107.46

4,428

159.28

3,966

109.02

1,433

102.36

2015/16

5,632

94.83

3,843

108.96

5,283

190.04

859.00

100.00

3,961

108.88

1,442

103.00

2016/17

5,222

87.93

3,769

106.86

2,348

84.46

1129.00

131.43

3,979

109.37

1,574

112.43

2017/18

3,727

62.75

3,526

99.97

1,545

55.58

2743.00

319.32

3,822

105.06

1,549

110.64

Patie

nts w

ith a kn

own

weigh

tYe

ar

Plasma

Recombina

nt

(excluding inve

stigational)

Inve

stigationa

l rFV

IIITo

tal

Enha

nced

Half‐L

ife FV

III

1,250

1,300

1,350

1,400

1,450

1,500

1,550

1,600

1,650

1,700

0

1,000

2,000

3,000

4,000

5,000

6,000

7,000

2012

/13

2013

/14

2014

/15

2015

/16

2016

/17

2017

/18

Patients (n)

Median Units per Kg

Time Pe

riod

Reco

mbinant

Plasm

aInve

stigational

Enhan

ced Half‐Life

Patients w

ith a known w

eight

Tab

le 4

a T

reat

men

t int

ensi

ty o

f pat

ient

s w

ith s

ever

e ha

emop

hilia

A tr

eate

d w

ith s

tand

ard

FV

III, w

ith n

o in

hibi

tor

– 201

2/13

-

2017

/18

<18 Ye

ars

≥18 ye

ars

<18 Ye

ars

≥18 ye

ars

<18 Ye

ars

≥18 ye

ars

<18 Ye

ars

≥18 ye

ars

2012/13

96,937,920

240,820,413

557

970

174,036

248,268

100.0

100.0

2013/14

103,552,817

266,497,744

582

1,028

177,926

259,239

102.2

104.4

2014/15

108,337,422

290,704,773

578

1,070

187,435

271,687

107.7

109.4

2015/16

107,747,690

306,430,481

574

1,109

187,714

276,312

107.9

111.3

2016/17

109,410,917

317,871,728

570

1,149

191,949

276,651

110.3

111.4

2017/18

97,546,514

290,942,676

514

1,128

189,779

257,928

109.0

103.9

Patie

nts

(n)

Trea

tmen

t Inten

sity

(Units/Pt)

Chan

ge in

trea

tmen

t intensity

since

201

2/13

(%)

FVIII Units

Treatmen

t Pe

riod

Tabl

e 4a

: T

his

show

s th

at S

HL

FV

III (

stan

dard

hal

f-lif

e F

VIII

) tr

eatm

ent i

nten

sity

(un

its/p

atie

nt/y

ear)

for

seve

re h

aem

ophi

lia A

has

incr

ease

d by

9%

in c

hild

ren

and

4% in

adu

lts w

ith s

ever

e ha

emop

hilia

A (

but n

o in

hibi

tor)

in th

e la

st s

ix y

ears

.

The

incr

ease

in t

reat

men

t in

tens

ity in

adu

lts w

ith s

ever

e ha

emop

hilia

A p

roba

bly

refle

cts

a co

mbi

natio

n of

incr

ease

d bo

dyw

eigh

t, in

crea

sed

use

of p

roph

ylax

is a

nd in

crea

sed

inte

nsity

of p

roph

ylax

is.

At t

he s

ame

time,

the

num

ber

of a

dult

patie

nts

trea

ted

with

SH

L F

VIII

has

incr

ease

d by

16%

, muc

h of

whi

ch is

pro

babl

y ca

used

by

inw

ard

mig

ratio

n.

The

incr

ease

in t

he n

umbe

r of

SH

L F

VIII

uni

ts is

sued

up

until

201

6/17

was

at

trib

utab

le t

o a

com

bina

tion

of g

reat

er t

reat

men

t in

tens

ity a

nd a

sig

nific

ant

incr

ease

in

the

num

ber

of p

atie

nts

with

sev

ere

haem

ophi

lia A

tr

eate

d. H

owev

er, t

he n

umbe

r of

SH

L F

VIII

uni

ts is

sued

fell

in 2

017/

18 fo

llow

ing

the

intr

oduc

tion

of E

HL

FV

III (

enha

nced

hal

f-lif

e F

VIII

).

Page | 25


Tab

le 4

b T

reat

men

t int

ensi

ty o

f pat

ient

s w

ith s

ever

e ha

emop

hilia

A tr

eate

d w

ith e

nhan

ced

half-

life

FV

III, w

ith n

o in

hibi

tor

– 20

15/1

6 -

2017

/18

<18 Ye

ars

≥18 ye

ars

<18 Ye

ars

≥18 ye

ars

<18 Ye

ars

≥18 ye

ars

<18 Ye

ars

≥18 ye

ars

2016/17

4,533,066

7,266,250

6467

70,829

108,451

100.0

100.0

2017/18

21,024,200

36,708,348

153

185

137,413

198,424

194.0

183.0

Chan

ge in

trea

tmen

t intensity

since

201

5/16

(%)

Treatmen

t Pe

riod

Enha

nced

half‐life FV

III Units

Patie

nts

(n)

Trea

tmen

t Inten

sity

(Units/Pt)

Tabl

e 4b

sho

ws

the

intr

oduc

tion

of E

HL

FV

III fo

r th

e tr

eatm

ent o

f sev

ere

haem

ophi

lia A

from

Sep

tem

ber

2016

to A

pril

2018

. T

he n

umbe

r of

pa

tient

s tr

eate

d in

crea

sed

by 1

58%

ove

r th

e la

st tw

o ye

ars

as m

ore

patie

nts

wer

e ch

ange

d to

the

prod

uct.

The

dra

mat

ic, a

lmos

t dou

blin

g of

tr

eatm

ent i

nten

sity

ove

r th

e tw

o ye

ars

is d

ue to

the

intr

oduc

tion

of E

HL

FV

III o

nly

halfw

ay th

roug

h th

e fir

st y

ear.

NO

TE

: Tab

les

4a &

4b

and

tabl

es 5

a &

5b

– Pat

ient

s tr

eate

d w

ith b

oth

EH

L an

d no

n-E

HL

FV

III a

nd th

eir

usag

e ar

e co

unt i

n bo

th ta

bles

.

Page | 26


Tab

le 5

a T

reat

men

t in

tens

ity o

f pat

ient

s w

ith m

oder

ate

haem

ophi

lia A

tre

ated

with

sta

ndar

d F

VIII

, with

no

inhi

bito

r –

2012

/13

- 20

17/1

8

<18 Ye

ars

≥18 ye

ars

<18 Ye

ars

≥18 ye

ars

<18 Ye

ars

≥18 ye

ars

<18 Ye

ars

≥18 ye

ars

2012/13

10,401,048

40,611,931

140

346

74,293

117,376

100.0

100.0

2 (1,4)

2013/14

12,674,000

42,371,979

149

361

85,060

117,374

114.5

100.0

2 (1,4)

2014/15

14,624,450

43,322,246

147

361

99,486

120,006

133.9

102.2

2.4 (1,4)

2015/16

14,164,750

47,552,983

138

376

102,643

126,471

138.2

107.7

3 (1,4)

2016/17

14,446,470

49,180,519

135

364

107,011

135,111

144.0

115.1

2.1 (1,4)

2017/18

12,471,928

43,715,859

139

353

89,726

123,841

120.8

105.5

3 (1,4)

Med

ian

(IQR)

Chan

ge in

trea

tmen

t intensity

since

201

2/13

(%)

Treatmen

t Pe

riod

FVIII Units

Patie

nts T

reated

(n)

Trea

tmen

t Inten

sity

(Units/Pt)

Tabl

e 5a

: Thi

s ta

ble

show

s tr

ends

in tr

eatm

ent i

nten

sity

of m

oder

ate

seve

rity

haem

ophi

lia o

ver

the

last

six

yea

rs.

Onl

y pa

tient

s tr

eate

d du

ring

this

tim

e ar

e in

clud

ed.

How

ever

, a r

ange

of b

asel

ine

fact

or V

III le

vels

and

ble

edin

g ph

enot

ypes

will

be

incl

uded

in th

is d

ata

from

pat

ient

s on

re

gula

r pr

ophy

laxi

s to

tho

se r

equi

ring

only

occ

asio

nal t

reat

men

t. T

his

rend

ers

the

data

mor

e di

fficu

lt to

inte

rpre

t an

d im

poss

ible

to

com

pare

di

rect

ly w

ith t

he r

elat

ivel

y m

ore

hom

ogen

eous

gro

up o

f pa

tient

s w

ith s

ever

e ha

emop

hilia

A.

Alth

ough

SH

L F

VIII

tre

atm

ent

inte

nsity

of

mod

erat

e ha

emop

hilia

app

ears

to

have

incr

ease

d in

bot

h ag

e-gr

oups

prio

r to

the

intr

oduc

tion

of E

HL

FV

III,

in 2

017/

18 it

was

less

tha

n 50

%

of t

hat

foun

d in

pat

ient

s w

ith s

ever

e ha

emop

hilia

. F

urth

erm

ore,

Hae

mtr

ack

data

sug

gest

s th

at p

atie

nts

with

mod

erat

e se

verit

y ha

emop

hilia

m

ay b

e re

lativ

ely

unde

r-tr

eate

d. T

his

is a

n ar

ea o

f hae

mop

hilia

ther

apy

that

req

uire

s cl

oser

inve

stig

atio

n.


Page | 27

Tab

le 5

b T

reat

men

t int

ensi

ty o

f pat

ient

s w

ith m

oder

ate

haem

ophi

lia A

trea

ted

with

enh

ance

d ha

lf-lif

e F

VIII

, with

no

inhi

bito

r –

2016

/17

- 20

17/1

8

<18 Ye

ars

≥18 ye

ars

<18 Ye

ars

≥18 ye

ars

<18 Ye

ars

≥18 ye

ars

<18 Ye

ars

≥18 ye

ars

2016/17

485,000

1,288,000

916

53,889

80,500

100.0

100.0

2017/18

1,222,500

7,123,500

1135

111,136

203,529

206.2

252.8

Chan

ge in

trea

tmen

t intensity

since

2015/16 (%)

Treatmen

t Pe

riod

Enha

nced

half‐life FV

III Units

Patie

nts

(n)

Trea

tmen

t Inten

sity

(Units/Pt)

Tabl

e 5b

: T

able

5b

Illus

trat

es t

he i

ntro

duct

ion

of E

HL

FV

III t

o a

rela

tivel

y sm

all

grou

p of

pat

ient

s w

ith m

oder

ate

seve

rity

haem

ophi

lia A

be

twee

n S

epte

mbe

r 20

16 a

nd A

pril

2018

. T

his

appe

ars

to s

how

a m

arke

d in

crea

se i

n tr

eatm

ent

inte

nsity

in

both

age

gro

ups

due

to t

he

intr

oduc

tion

of E

HL

FV

III o

nly

halfw

ay th

roug

h th

e fir

st y

ear.

Page | 28



Page | 29

Figure 6 Median usage of factor VIII: UK patients with severe haemophilia A without inhibitors broken down by age, 2012/13 – 2017/18

N.B. figure based on total usage, not units/kg

Data table for Figure 6

Figure 6: This shows median, IQR and arithmetic range of factor VIII usage by all UK patients with severe haemophilia A without inhibitors, broken down by age and year. This shows a general upward trend in the number of units issued per year in all age groups, similar to table 4a (see data table). This is consistent with the earlier suggestion that prophylaxis may be used more extensively than previously in older age groups. Since prophylaxis has been the standard of care in children since 1996, this increase in treatment intensity amongst children suggests increased intensity of prophylaxis over the years in these groups.

Age Range(years)

Change in median unitsfrom 2012/13 to 2017/18

(%)0‐9 22.9

10‐19 12.9

20‐49 4.2

50‐59 ‐0.3

60+ 22

Fig

ure

7 P

atie

nts

with

sev

ere

/ mod

erat

e / m

ild h

aem

ophi

lia A

trea

ted

with

FV

III b

y U

K h

aem

ophi

lia c

entr

es –

2009

/10

– 201

7/18

Haem

ophilia

A

In Reg

% ch

ange

In Reg

% ch

ange

In Reg

% ch

ange

In Reg

% ch

ange

nn

(%)

since

2008

/09

nn

(%)

since

2008

/09

nn

(%)

since

2008

/09

nn

(%)

since

2008

/09

2008/09

1653

1516

(91.7)

100.0

801

522(65.2)

100.0

3071

558(18.2)

100.0

558

22(3.9)

100.0

2009/10

1683

1542

(91.6)

101.7

807

501(62.1)

96.0

3120

615(19.7)

110.2

584

27(4.6)

122.7

2010/11

1714

1578

(92.1)

104.1

810

510(63.0)

97.7

3171

638(20.1)

114.3

602

26(4.3)

118.2

2011/12

1746

1623

(93.0)

107.1

807

523(64.8)

100.2

3233

641(19.8)

114.9

615

20(3.3)

90.9

2012/13

1777

1638

(92.2)

108.0

806

497(61.7)

95.2

3360

638(19.0)

114.3

755

21(2.8)

95.5

2013/14

1830

1701

(93.0)

112.2

804

526(65.4)

100.8

3412

643(18.8)

115.2

876

21(2.4)

95.5

2014/15

1877

1746

(93.0)

115.2

804

526(65.4)

100.8

3538

638(18.0)

114.3

1083

21(1.9)

95.5

2015/16

1934

1793

(92.7)

118.3

806

526(65.3)

100.8

3661

660(18.0)

118.3

1209

21(1.7)

95.5

2016/17

1969

1833

(93.1)

120.9

805

513(63.7)

98.3

3709

638(17.2)

114.3

1344

25(1.9)

113.6

2017/18

2015

1876

(93.1)

123.7

818

530(64.8)

101.5

3792

713(18.8)

127.8

1463

32(2.2)

145.5

Num

ber o


vel (IU/dl))

<11 ‐ 5

>5 & <40

≥ 40

Treatmen

t Ye

ar

Trea

ted

Trea

ted

Trea

ted

Trea

ted

Tabl

e 6

(ove

rleaf

): T

his

show

s fa

ctor

VIII

usa

ge b

y co

untr

y an

d co

mm

issi

onin

g re

gion

, ran

ked

by th

e m

ean

num

ber

of u

nits

issu

ed p

er p

atie

nt

with

sev

ere

haem

ophi

lia A

. T

his

sugg

ests

a w

ider

ran

ge o

f clin

ical

pra

ctic

e fr

om r

egio

n to

reg

ion

as o

bser

ved

last

yea

r.

Usa

ge p

er c

apita

of

popu

latio

n is

als

o re

port

ed.

Usa

ge p

er c

apita

for

Sco

tland

is b

roke

n do

wn

into

Eas

t an

d W

est

of S

cotla

nd.

Nor

ther

n Ir

elan

d an

d E

ngla

nd a

re fa

irly

clos

ely

mat

ched

.

Page | 30


Tab

le 6

F

acto

r V

III u

sage

by

regi

on fo

r pa

tient

s w

ith s

ever

e ha

emop

hilia

A (

incl

. tre

atm

ent f

or in

hibi

tors

and

EH

L-V

III),

201

7/18

Region

Gen

eral

Popu

latio

n

Patie

nts

trea

ted

(n)

Total FVIII

(IU)

Mea

n Usage

FVIII Units

Per C

apita

East of En

glan

d6,168,432

132

42,484,070

321,849

6.89

Yorkshire and the Humber

5,450,130

131

41,780,500

318,935

7.67

London

8,825,001

317

95,341,906

300,763

10.80

North East

2,644,727

6017,102,000

285,033

6.47

South East

9,080,825

299

77,784,940

260,150

8.57

South W

est

5,559,316

136

34,887,000

256,522

6.28

North W

est

7,258,627

194

43,657,000

225,036

6.01

East M

idlands

4,771,666

161

34,194,128

212,386

7.17

West M

idlands

5,860,706

159

31,386,082

197,397

5.36

Englan

d55,619,430

1,589

418,617,626

263,447

7.53

Northern Ireland

1,870,834

7215,002,250

208,365

8.02

Scotlan

d East

3,051,000

7722,504,000

292,260

7.38

Scotlan

d W

est

2,373,800

6115,223,250

249,561

6.41

Wales

3,125,165

7618,614,580

244,929

5.96

United King

dom

66,040,229

1,875

489,961,706

261,313

7.42

Seve

re Hae

mop

hilia

A

Eng

lish

regi

ons

rank

ed b

y m

ean

usag

e

Sou

rce

accr

edita

tion:

Pop

ulat

ion

Est

imat

es fo

r UK

, Eng

land

and

Wal

es, S

cotla

nd a

nd N

orth

ern

Irel

and:

Mid

-201

7: O

ffice

for N

atio

nal S

tatis

tics

licen

sed

unde

r the

Ope

n G

over

nmen

t Lic

ence

v.3

.0.

© C

row

n co

pyrig

ht 2

018

Mid

-201

7 po

pula

tion

estim

ates

Sco

tland

sup

plie

d by

Nat

iona

l Rec

ords

of S

cotla

nd u

nder

the

Ope

n G

over

nmen

t Lic

ence

v3.

0 ©

Cro

wn

Cop

yrig

ht 2

018

NO

TE

: Pat

ient

s ar

e al

loca

ted

to e

ach

regi

on b

ased

on

thei

r ho

me

post

code

, rat

her t

han

whe

re th

ey w

ere

trea

ted

Page | 31



Page | 32

Note on Figures 8a&b and Figures 9a&b

Patients treated at more than one centre during the year have all their usage attributed to the centre where they received the most units.

Centres with 4 or fewer patients or between 5-9 patients have been aggregated, and all other centres reported individually.

The boxes show the median and 25th and 75th percentiles, and the whiskers show the arithmetic range of FVIII usage, excluding outliers.

Indicated outside values show where a patient's usage is more than 1.5 times the interquartile range (IQR) from the nearest quartile at centre level rather than by reference to practice in the UK as a whole. Outliers in some centres therefore use less than patients not identified as outliers in other centres.

The vertical green line indicates the 95th percentile of units for the whole group (14,048 units per kilogram)

The vertical red line indicates a break in the axis in order to illustrate extreme outliers.

Figure 8a Annual FVIII usage (IU/Kg/Pt) in patients with severe haemophilia A aged under 18 years with no current inhibitor, by centre, ranked by

median usage

N.B: The 95th percentile of units = 13,846 units per kilogram

Figure 8a: This shows factor VIII usage per kilogram per patient by haemophilia centre, ranked by median usage, in patients with severe haemophilia A aged under 18 years old with no reported current inhibitor and an up-to-date bodyweight reported in the previous 12 months.


Page | 33

This shows a 2-fold range in median treatment intensity between centres This implies a wide range in the intensity of prophylaxis used for children with haemophilia in the UK. Most centres have broadly similar treatment intensity, as one would expect, given that prophylaxis is the standard of care. The difference in practice at the extremes is not easily explained for some centres. However, those centres such as Great Ormond Street, who conduct a far greater number of Immune Tolerance Induction procedures than other paediatric centres, will be expected to have high median usage. Although this chart excludes patients with a reported current inhibitor, they may have a higher proportion of patients with unreported low-level inhibitors. It is now well recognised that some patients who fulfil the internationally recognised criteria for tolerance (half-life greater than eight hours), and who have traditionally been thought to be inhibitor free, continue to have low level inhibitor activity, which is too low to detect in the Bethesda assay but high enough to impair factor VIII pharmacokinetics and increase factor VIII consumption. Figure 12 shows that patients aged under 18 years with a past inhibitor history, but currently thought to be inhibitor-free, nevertheless use on average 23.5% more factor VIII than those with no past inhibitor history (p<0.005).

Summary statistics for this chart are presented in the accompanying data table.

Data table for Figures 8a & b

Haemophilia CentrePatients treated

Patients treated with

weight reported

Total UnitsMedian Units

Median Units/Kg

Belfast Adults' 11 9 2,902,000 268,000 3,824

Belfast Children's 14 3 1,502,000 103,250 3,435

Birmingham 45 38 6,593,701 132,000 3,833

Bristol 23 19 5,079,750 189,000 5,976

Cambridge 21 21 3,294,000 108,000 4,930

Canterbury 15 8 2,951,500 142,750 6,620

Cardiff 13 13 3,153,000 216,500 5,386

Edinburgh 10 10 2,590,500 92,125 5,293

Glasgow 26 26 5,906,500 146,000 6,623

Great Ormond Street 83 78 22,990,341 242,000 6,810

Leeds 23 22 5,344,250 225,000 7,675

Leicester 11 10 1,420,800 113,250 5,121

Liverpool 25 23 4,198,500 112,500 5,646

Manchester 50 45 8,023,000 134,875 5,027

Newcastle upon Tyne 19 19 3,732,250 195,000 3,963

North Hampshire 19 19 3,945,750 202,000 5,449

Nottingham 17 17 2,514,000 121,000 4,394

Oxford 32 32 6,873,750 193,250 4,535

Royal London 19 18 3,567,872 156,000 3,518

Sheffield 19 8 3,489,000 126,250 4,170

St Thomas' 24 14 3,898,000 156,500 4,785

Centres with <=4 patients meeting criteria 17 12 5,187,250 312,500 6,136

Centres with 5‐9 patients meeting criteria 53 47 9,583,250 162,000 5,141


Page | 34

Figure 8b Annual FVIII usage (IU/Pt) in patients with severe haemophilia A aged under 18 years with no current inhibitor, by centre, ranked by median

usage per patient

N.B: The 95th percentile of units = 452,500 IU

Figure 8b: This shows usage per patient aged under 18 years by centre, for patients with severe haemophilia A with no reported current inhibitor as in the previous figure but not corrected for bodyweight. It shows a three-fold range in median units used per patient between centres, and interpretation is similar to the previous figure, though the sample size is slightly larger since all patients are included and not just those for whom current bodyweight is known.


Page | 35

Figure 9a Annual FVIII usage (IU/Kg/Pt) in patients with severe haemophilia A aged 18 years or more with no current inhibitor, by centre, ranked by

median usage

N.B: The 95th percentile of units = 6,955 IU kilogram

Figure 9a: This shows factor VIII usage per kilogram per patient by haemophilia centre, ranked by median usage, in patients with severe haemophilia A aged 18 years or more with no reported current inhibitor, and an up-do-date reported bodyweight.

Note that the 95th percentile for adults is lower than for children. This is partly a reflection of the shorter half-life found in small children, who require larger doses per kilogram of bodyweight. The adult outliers also show that a small number of patients, use a great deal of factor VIII, despite having apparently no reported inhibitor in the year. The three extreme outlying users in excess of 15 thousand units per kilogram and a further 46 users in excess of 7 thousand units per kilogram will be the subject of a separate study, to gain a better understanding of the reasons for their unusually high factor usage.

The median treatment intensity range is approximately threefold. There is still a wide range in clinical practice from one centre to the next.


Page | 36

Data table for Figures 9a & b

Haemophilia CentrePatients treated

Patients treated with

weight reported

Total UnitsMedian Units

Median Units/Kg

Aberdeen 14 11 3,914,000 290,000 2,896

Belfast Adults' 46 41 10,088,750 224,000 2,583

Birmingham 73 54 15,415,000 200,500 2,036

Bristol 31 20 7,509,000 185,000 2,340

Cambridge 30 30 8,615,250 259,000 3,222

Canterbury 21 12 7,130,500 336,000 4,089

Cardiff 33 31 5,535,270 156,000 1,504

Coventry 12 12 2,618,500 226,500 3,165

Dundee 14 14 3,392,500 273,250 3,115

Edinburgh 22 22 8,035,000 281,000 3,856

Glasgow 43 43 11,802,500 245,000 2,938

Hammersmith 27 24 9,405,000 336,000 4,712

Kingston upon Hull 15 11 5,076,750 320,000 3,692

Leeds 38 33 14,878,500 360,000 4,276

Leicester 22 19 4,635,944 210,097 2,680

Liverpool 29 15 8,543,500 200,000 3,076

Manchester 79 69 18,674,750 239,500 2,829

Newcastle upon Tyne 42 39 12,920,250 285,000 3,061

North Hampshire 51 44 13,855,430 258,000 3,068

Nottingham 30 30 6,274,500 212,750 2,487

Oxford 97 92 22,705,900 239,000 2,836

Royal Free 135 130 45,621,641 326,000 4,186

Royal London 50 37 10,209,089 185,704 2,645

Sheffield 21 20 8,014,500 345,500 4,070

Southampton 14 10 3,466,500 176,000 2,944

St George's 32 29 4,943,250 144,000 1,819

St Thomas' 104 51 36,071,500 344,000 4,105

Centres with <=4 patients meeting criteria 35 26 9,390,250 220,000 3,117

Centres with 5‐9 patients meeting criteria 32 13 8,907,500 209,250 2,655


Page | 37

Figure 9b Annual FVIII usage (IU/Pt) in patients with severe haemophilia A aged 18 years or more with no current inhibitor, by centre, ranked by median

usage per patient

N.B: The 95th percentile of units = 573,000 IU

Figure 9b: This shows usage per patient aged 18 years or more by centre, for patients with severe haemophilia A with no reported current inhibitor not corrected for bodyweight. It shows a wide range in treatment intensity and interpretation is similar to the previous figure, though the sample size is larger since all patients are included and not just those for whom current bodyweight is known.


Page | 38

Figure 10 Median factor VIII units issued per kilogram body weight per year in patients with severe haemophilia A without inhibitors by age

Weight data are missing for 288/1781 patients

Figure 10: This shows the median factor VIII usage per kilogram bodyweight per year in UK patients with severe haemophilia A without inhibitors, broken down by age.

The most intensive general usage appears to be in children, as would be expected. Vial size is also an issue for small children since doses will often be rounded up because the range of available vial sizes does not make it possible to make small dose-adjustments in very small individuals.

Treatment intensity (IU/kg/year) appears to be relatively similar in all adult age-groups.


Page | 39

Figure 11 Median factor VIII units issued (IU/kg) in patients with severe haemophilia A without inhibitors aged 16 and over, by bodyweight

Weight data are missing for 223/1252

Figure 11: This shows median units per kilogram per year issued to UK patients with severe haemophilia A aged 16 and over without inhibitors, broken down by bodyweight. The total number of patients in each group is indicated by the number over each box. Since factor VIII recovery increases progressively as Body Mass Index (BMI) increases, one would expect factor VIII consumption per kilogram bodyweight to decline as bodyweight increases. This appears to be the case generally.

We presume that the `greater than 100 kg’ group will all be obese but since we do not record height, we cannot calculate BMI.


Page | 40

Figure 12 Patients with severe haemophilia A with no current inhibitor in the reporting year: median usage by inhibitor history

Mann-Whitney U test: Under 18 years: p<0.005 (significant); 18 years and over: p=0.03 (significant)

Figure 12: This shows median usage of factor VIII for UK patients with severe haemophilia without a current inhibitor. Usage is broken down by age (less than 18 years, and 18 years and older) and history of FVIII inhibitors. The number of subjects in each group is indicated by the number over each box.

This shows that children with a history of factor VIII inhibitors use significantly more factor VIII than those without such a history. The small difference seen between non-inhibitor and ex-inhibitor adults is also statistically significant (Mann-Whitney U test p<0.005 for children, and p=0.03 for adults). Whilst there are a number of possible explanations for this, it is suspected that reportedly “tolerant” ex-inhibitor patients will commonly have a relatively reduced half-life and low-level circulating factor VIII inhibitors, below the limit of detection of the current Bethesda assay, which are very gradually abolished by ongoing factor VIII prophylaxis.


Page | 41

Table 7 Products issued to treat haemophilia A (including inhibitors), 2017/18

2016/17 2017/18

Bayer Kogenate 19,542,086 11,569,000

Biotest Haemoctin 336,000 392,000

FVIII 8Y 221,510 127,590

Optivate 4,500,425 3,841,220

Helixate Nexgen 24,401,450 13,065,000

Riastap (g) 3 6

Alphanate 114,000 111,000

Fanhdi 19,616,500 14,553,040

NovoSeven (mg) 19,700 18,649

NovoEight ‐ 13,586,150

Nuwiq 6,013,280 10,922,016

Octanate 5,086,500 4,263,500

Wilate ‐ 6,000

Pfizer ReFacto AF 284,693,866 255,426,658

Roche Emicizumab (EAMS) (mg) ‐ 15,081

Advate 175,084,058 171,523,660

FVII ‐ 45,000

FEIBA 35,104,000 30,234,596

SOBI/Biogen Elocta 15,257,316 69,454,048

Desmopressin 23,767 29,394

Investigational Factor VIII 10,573,777 5,807,522

Investigational Factor VII * *

Other Investigational

Products * *

Various Manufacturers

Total Units Manufacturer Product

BPL

Shire

CSL Behring

Novo Nordisk

Octapharma

Grifols

Units in IU unless otherwise stated * Due to commercial sensitivities, units have been withheld


Page | 42

Table 7: This shows a breakdown of products, listed by supplier, issued to treat UK patients with haemophilia A in 2017/18, including those with inhibitors but excluding acquired haemophilia.

These figures have been cross-checked against sales figures supplied by the manufacturers for the same period. Whilst one would not expect a perfect match between NHD figures and the manufacturer’s sales figures, there is a very high level of correlation for all but the low usage products. These sales figures are not reported by agreement with suppliers for reasons of commercial sensitivity.

By and large, the plasma derived products listed were used for immune tolerance induction. The exception, Fanhdi, is also used for a group of patients without inhibitors attending a single centre in the South of England. The usage of Fanhdi has declined in the last three years.

The use of investigational factor VIII continues to decline as several clinical trials come to an end, so it is likely that the use of investigational factor VIII may decline further from its recent historic high. We have deliberately aggregated and anonymised investigational products to avoid any breach of individual centre’s confidentiality agreements and to take account of commercial sensitivities.

Emicizumab (Hemlibra®) is listed for the first time, having previously been unlicensed. This product became available on prescription in July for inhibitor patients and usage is expected to increase.

Tab

le 8

F

acto

r V

III u

nits

issu

ed b

y U

K h

aem

ophi

lia c

entr

es, b

y di

agno

sis.

201

7/18

Plasma

Recombina

ntInve

stigationa

lEn

hanced

Half‐

Life

Total

Hae

mophilia A

3,152

23,294,350

476,092,484

5,807,522

69,454,048

574,648,404

Acquired Hae

mophilia A

9

7,600

70,000

‐

‐

77,600

von W

illebrand disease

784

22,054,403

207,000

‐

‐

22,261,403

Acquired von W

illebrand Disease

34

980,500

3,000

‐

‐

983,500

Platelet‐type Pseudo von W

illebrand Disease

2

5,000

‐

‐

‐

5,000

Probab

le von W

illebrand disease

1

2,000

‐

‐

‐

2,000

F.V deficiency

1

‐

39,000

‐

‐

39,000

F.VII deficiency

1

‐

1,250

‐

‐

1,250

Combined V+V

III D

eficiency

11

‐

61,000

‐

‐

61,000

Co‐inherited diagn

oses

26

405,900

573,500

‐

593,000

1,572,400

Miscellan

eous

5

118,060

‐

‐

‐

118,060

Total

4,026

46,867,813

477,047,234

5

,807,522

70,047,048

599,769,617

FVIII (IU)

Coagulation De

fect

Patie

nts

Trea

ted

Pro

duct

s co

ntai

ning

VW

F a

s w

ell a

s F

VIII

are

rep

orte

d in

FV

III u

nits

Tabl

e 8:

T

his

show

s fa

ctor

VIII

con

cent

rate

use

bro

ken

dow

n ac

cord

ing

to d

iagn

osis

tre

ated

, in

clud

ing

appa

rent

ly a

nom

alou

s us

e re

port

ed

to t

he N

HD

. P

rodu

cts

used

to

trea

t vo

n W

illeb

rand

dis

ease

whi

ch in

clud

e V

WF

and

FV

III a

re in

clud

ed a

nd a

re r

epor

ted

in F

VIII

uni

ts.

It

is

perh

aps

surp

risin

g th

at s

uch

a la

rge

amou

nt o

f re

com

bina

nt f

acto

r V

III w

as u

sed

for

the

trea

tmen

t of

von

Will

ebra

nd d

isea

se,

give

n th

at it

co

ntai

ns n

o vo

n W

illeb

rand

fact

or.

Mor

e de

tail

on th

e us

e of

thes

e pr

oduc

ts to

trea

t VW

D is

giv

en w

ith ta

ble

16.

* P

oten

tially

ano

mal

ous

use

of fa

ctor

VIII

in T

able

8 is

acc

ount

ed fo

r as

follo

ws:

FV

Def

icie

ncy:

Pat

ient

with

FV

def

icie

ncy

deve

lope

d a

mild

inhi

bito

r po

st-p

artu

m a

nd w

as d

iagn

osed

with

Acq

uire

d H

aem

A.

Mis

cella

neou

s bl

eedi

ng d

isor

ders

: th

rom

botic

thro

mbo

cyto

peni

a pu

rpur

a.

Page | 43


Baye

r -Re

com

bina

nt

1.93

%

Biot

est -

Plas

ma

0.07

%

BPL -

Plas

ma

0.68

% CSL B

ehri

ng -

Plas

ma

2.65

%CS

L Beh

ring

-Re

com

bina

nt

2.19

%G

rifo

ls -

Plas

ma

2.53

%

Nov

o N

ordi

sk -

Reco

mbi

nant

2.

27%

Oct

apha

rma

-Pla

sma

1.89

%

Oct

apha

rma

-Re

com

bina

nt

1.82

%

Pfize

r -Re

com

bina

nt

42.6

1%

Shir

e -R

ecom

bina

nt

28.7

2%

SOBI

/Bio

gen

-Enh

ance

d H

alf-L

ife

11.6

8%In

ves�

ga�o

nal r

FVIII

0.

97%

Figu

re 1

3 M

arke

t Sha

re o

f fac

tor V

III c

once

ntra

tes

issu

ed b

y U

K h

aem

ophi

lia c

entre

s, 2

017/

18

Man

uact

urer

-Pro

duct

Typ

ePa

tient

s(n

)

Baye

r - R

ecom

bina

nt13

1

Bi

otes

t - P

lasm

a1

BP

L - P

lasm

a15

CSL B

ehrin

g - P

lasm

a60

1

CS

L Beh

ring

- Rec

ombi

nant

134

Grifo

ls - P

lasm

a57

Nov

o N

ordi

sk -

Reco

mbi

nant

237

Oct

apha

rma

- Pla

sma

260

Oct

apha

rma

- Rec

ombi

nant

57

Pfi

zer -

Rec

ombi

nant

1,49

8

Shire

- Re

com

bina

nt1,

181

SO

BI/B

ioge

n - E

nhan

ced

Half-

Life

404

Inve

s�ga�o

nal r

FVIII

47

To

tal

4,62

3

Figu

re 1

3: T

his

show

s th

e m

arke

t bre

akdo

wn

of

fact

or V

III c

once

ntra

tes

issu

ed fo

r all

diag

nose

s,

incl

udin

g in

hibi

tor

patie

nts.

Pla

sma-

deriv

ed

fact

or V

III is

gen

eral

ly u

sed

for t

reat

men

t of v

on

Will

ebra

nd d

isea

se o

r fo

r im

mun

e to

lera

nce

indu

ctio

n, b

ut o

ne c

entre

has

a s

igni

fican

t us

e of

Fa

nhdi

fo

r no

n-in

hibi

tor

patie

nts

with

ha

emop

hilia

A a

nd o

ne o

r tw

o ot

her

isol

ated

pa

tient

s in

oth

er c

entre

s us

e pl

asm

a-de

rived

pr

oduc

ts a

s th

eir r

outin

e re

plac

emen

t the

rapy

.

| egaP 44



Page | 45

2.2 Haemophilia B

Tab

le 9

P

atie

nts

with

con

geni

tal h

aem

ophi

lia B

(in

clud

ing

carr

iers

) re

gist

ered

and

trea

ted,

201

7/18

MF

Total

MF

Total

MF

Total

MF

Total

MF

Total

MF

Total

<18 years

122 ‐

122 81 ‐

81

100 59 159 5

34

39

‐ ‐

‐

308 93 401

≥18 years

237 1 238 255 5 260 395 219 614 37 239 276 1

5

6

925 469 1,394

Total

359 1

360 336 5 341 495 278 773

4

2 273 315

1 5

6 1,233 562

1,795

<18 years

8

‐

8

5

‐

5

8

10

18

1

8

9

‐ ‐

‐

22 18

40

≥18 years

2

‐

2

4

‐

4

9

6

15

2

20

22

‐ ‐

‐

17 26

43

Total

1

0 ‐ 10

9 ‐

9 1

7 1

6 3

3 3 28

3

1 ‐ ‐

‐ 3

9 4

4 8

3

<18 years

113 ‐

113 43 ‐

43

30 5

35

‐ ‐

‐

‐ ‐

‐

186 5 191

≥18 years

224 ‐

224 134 1 135 110 29 139 6

6

12

1

‐

1

475 36 511

Total

337 ‐

337 177 1 178 140 3

4 174 6 6

1

2 1 ‐

1 661 41

702

<18 years

109 ‐

109 42 ‐

42

30 5

35

‐ ‐

‐

‐ ‐

‐

181 5 186

≥18 years

217 ‐

217 134 1 135 110 28 138 6

5

11

1

‐

1

468 34 502

Total

326 ‐

326 176 1 177 140 3

3 173 6 5

1

1 1 ‐

1 649 39

688

Total In Register

New Registrations *

Treated in

year**

Treated with

concentrate in

year**

Hae

mop

hilia

B

Age

Ra

nge

Num

ber o

f Patients (Factor IX

leve

l (IU/dl))

< 1

1 ‐ 5

>5 & <40

≥ 40

Unk

nown

Total

* N

ew re

gist

ratio

ns a

re a

sub

set o

f the

‘In

Reg

iste

r’ nu

mbe

rs

** T

reat

ed in

clud

es p

atie

nts

‘In R

egis

ter’

and

‘New

Reg

istr

atio

ns’

Tabl

e 9:

T

his

show

s th

e nu

mbe

r of

pat

ient

s w

ith h

aem

ophi

lia B

(in

clud

ing

carr

iers

and

def

icie

nt f

emal

es),

bro

ken

dow

n by

sev

erity

, ge

nder

an

d ag

e.

Pat

ient

s ne

wly

reg

iste

red

are

also

sho

wn,

as

are

the

num

bers

tre

ated

. T

he n

umbe

r of

reg

iste

red

patie

nts

with

hae

mop

hilia

B

cont

inue

s to

ris

e, e

spec

ially

non

-sev

ere

haem

ophi

lia B

, whi

ch m

ay p

revi

ousl

y ha

ve b

een

unde

rdia

gnos

ed.

Page | 46



Page | 47

Figure 14 Carriers of haemophilia B currently registered and newly registered, by baseline factor IX level, 2017/18

0

20

40

60

80

100

120

140

160

<2 2‐9 10‐19 20‐29 30‐39 40‐49 50+ N/K

1

12

40

86

129

104

142

40 0 16 9 12

16

0

Patien

ts (n

)

Factor FIX level (IU/dl)

Haemophilia B CarrierIn Register

(excl. new registrations)

Haemophilia B CarrierNew Registrations

<2 2‐9 10‐19 20‐29 30‐39 40‐49 50+ N/KGrand Total

Haemophilia B Carrier

In Register

(excl. new registrations)

1 12 40 86 129 104 142 4 518

Haemophilia B Carrier

New Registrations0 0 1 6 9 12 16 0 44

Total 1 12 41 92 138 116 158 4 562

Diagnosis Number of Patients (Factor IX level (IU/dl))

N.B: Includes carrier of haemophilia B and females with FIX deficiency

Figure 14: This shows the distribution of reported factor IX levels amongst registered carriers of haemophilia B in the UK. Carriers with normal factor IX levels are still under-represented because these were not registered until relatively recently. All carriers should be registered.

It is interesting that there is a relatively large number of very low-level carriers. These mostly have an extreme degree of lyonisation but some are homozygous products of consanguineous unions. In some cases, the level is not known to us, either because the patient is too young to be tested or because a test result has been inadvertently omitted.

Tab

le 1

0 N

ew r

egis

trat

ions

of h

aem

ophi

lia B

(in

clud

ing

carr

iers

), b

y ag

e at

mid

-yea

r, g

ende

r an

d se

verit

y, 2

017/

18

Hae

mop

hilia

B MF

Total

MF

Total

MF

Total

MF

Total

MF

Total

0 ‐ < 2

8

‐

8

5

‐

5

2

2

4

1

2

3

16

4

20

2 : 4

‐

‐

‐

‐

‐

‐

2

1

3

‐

‐

‐

2

1

3

5 : 9

‐

‐

‐

‐

‐

‐

2

3

5

‐

4

4

2

7

9

10 : 19

1

‐

1

‐

‐

‐

2

4

6

1

4

5

4

8

12

20 : 29

‐

‐

‐

2

‐

2

2

‐

2

1

4

5

5

4

9

30 : 39

‐

‐

‐

1

‐

1

4

1

5

‐

5

5

5

6

11

40 : 49

‐

‐

‐

1

‐

1

1

1

2

‐

‐

‐

2

1

3

50 : 59

1

‐

1

‐

‐

‐

‐

1

1

‐

3

3

1

4

5

60 : 69

‐

‐

‐

‐

‐

‐

2

1

3

‐

4

4

2

5

7

70 +

‐

‐

‐

‐

‐

‐

‐

2

2

‐

2

2

‐

4

4

Total

100

109

09

1716

333

2831

3944

83

Total

Num

ber o

f Patients (Factor IX

leve

l (IU/dl))

Age

(yea

rs)

< 1

1 ‐ 5

> 5 & < 40

≥ 40

Tabl

e 10

: T

his

show

s ne

w r

egis

trat

ions

of h

aem

ophi

lia B

bro

ken

dow

n by

rep

orte

d se

verit

y an

d ag

e at

mid

-yea

r ye

ar (

30/0

9/20

17).

The

two

patie

nts

with

sev

ere

dise

ase

regi

ster

ed a

fter

the

age

of t

wo

wer

e bo

rn o

utsi

de t

he E

U.

Les

s se

vere

dis

ease

will

ofte

n pr

esen

t at

a la

ter

age

and

we

have

not

inve

stig

ated

the

prop

ortio

n of

that

gro

up w

hich

is n

ativ

e to

the

UK

.

Page | 48



Page | 49

Figure 15a Trend in numbers of severe haemophilia B patients aged 60 years and above, 1977 – 2017/18 (including HIV +ve pts)

N.B. Carriers are included in Figures 15a – 15c

Figure 15a: This shows the trend in numbers of patients aged over 60 years with severe haemophilia B since 1977. This shows a fourfold increase over the past 40 years, presumably attributable to increased life-expectancy.

Figure 15b (overleaf): This shows a similar bar diagram of patients with moderate severity haemophilia B showing an almost fourfold increase in patients aged over 60 years with moderate severity haemophilia B during the past 40 years. This will reflect a combination of better diagnosis, more complete registration and improved life expectancy.

Figure 15c (overleaf): This shows the trend in numbers of patients aged over 60 years with mild haemophilia B in the register since 1977. This shows an approximately twelve-fold increase over the past 40 years. This probably reflects a relatively modest increase in life expectancy coupled with increased diagnosis and reporting of mild haemophilia B.


Page | 50

Figure 15b Trend in numbers of moderate haemophilia B patients aged 60 years and above, 1977 – 2017/18 (including HIV +ve pts)

Figure 15c Trend in numbers of mild haemophilia B patients aged 60 years and above, 1977 – 2017/18 (including HIV +ve pts)

Figu

re 1

6 Fa

ctor

IX u

nits

issu

ed b

y U

K h

aem

ophi

lia c

entre

s to

trea

t hae

mop

hilia

B, 1

993

– 201

7/18

Figu

re 1

6: S

how

s U

K fa

ctor

IX u

sage

for a

ll di

agno

ses

from

199

3 to

201

7/18

. Th

e nu

mbe

r of p

atie

nts

repo

rted

to h

ave

been

trea

ted

is s

how

n by

the

blue

line

usi

ng a

sec

onda

ry a

xis.

Use

of r

ecom

bina

nt S

HL

FIX

red

uced

by

29%

bet

wee

n 20

16/1

7 an

d 20

17/1

8 an

d us

e of

EH

L FI

X

(sho

wn

in g

reen

) inc

reas

ed b

y 32

0% in

the

sam

e pe

riod.

Ove

rall,

fact

or IX

con

sum

ptio

n ha

s de

clin

ed a

s a

dire

ct c

onse

quen

ce o

f the

gra

dual

in

trodu

ctio

n of

EH

L FI

X p

rodu

cts,

whi

ch a

re p

resc

ribed

gen

eral

ly in

low

er d

oses

/kg/

wee

k th

an s

tand

ard

prod

ucts

.

| egaP 15


0100

200

300

400

500

600

700

800

0102030405060708090100

Pa�ents (n)

Units(millions)

Tim

e Pe

riod

Plas

ma

Reco

mbi

nant

Inve

s�ga�o

nal

EHL

Pa�e

nts t

reat

ed

Tab

le 1

1 F

acto

r IX

usa

ge b

y re

gion

for

patie

nts

with

sev

ere

haem

ophi

lia B

(in

cl. t

reat

men

t for

inhi

bito

rs a

nd E

HL-

IX),

201

7/18

Region

Gen

eral

Popu

latio

n

Patie

nts

trea

ted

(n)

Total FIX

(IU)

Mea

n Usage

FIX Units

Per C

apita

South W

est

5,559,316

163,742,500

233,906

0.67

London

8,825,001

5711,911,676

208,977

1.35

North W

est

7,258,627

295,709,250

196,871

0.79

Yorkshire and the Humber

5,450,130

264,898,900

188,419

0.90

West M

idlands

5,860,706

274,837,350

179,161

0.83

South East

9,080,825

569,578,358

171,042

1.05

East of En

glan

d6,168,432

386,454,065

169,844

1.05

North East

2,644,727

111,709,750

155,432

0.65

East M

idlands

4,771,666

253,586,613

143,465

0.75

Englan

d55,619,430

285

52,428,462

183,960

0.94

Northern Ireland

1,870,834

81,732,500

216,563

0.93

Scotlan

d East

3,051,000

121,493,250

124,438

0.49

Scotlan

d W

est

2,373,800

121,347,838

112,320

0.57

Wales

3,125,165

91,296,500

144,056

0.41

United King

dom

66,040,229

326

58,298,550

178,830

0.88

Seve

re Hae

mop

hilia

B

Eng

lish

regi

ons

rank

ed b

y m

ean

usag

e

Sou

rce

accr

edita

tion:

Pop

ulat

ion

Est

imat

es fo

r UK

, Eng

land

and

Wal

es, S

cotla

nd a

nd N

orth

ern

Irel

and:

Mid

-201

7: O

ffice

for N

atio

nal S

tatis

tics

licen

sed

unde

r the

Ope

n G

over

nmen

t Lic

ence

v.3

.0.

© C

row

n co

pyrig

ht 2

018

Mid

-201

7 po

pula

tion

estim

ates

Sco

tland

sup

plie

d by

Nat

iona

l Rec

ords

of S

cotla

nd u

nder

the

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n G

over

nmen

t Lic

ence

v3.

0 ©

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wn

Cop

yrig

ht 2

018

NO

TE

: Pat

ient

s ar

e al

loca

ted

to e

ach

regi

on b

ased

on

thei

r ho

me

post

code

, rat

her t

han

whe

re th

ey w

ere

trea

ted

Page | 52



Page | 53

Table 11 (previous page): This shows factor IX usage by commissioning region. This shows similar variation in treatment intensity to that observed with haemophilia A, although patient numbers for this diagnosis are very much smaller and so between-region comparisons of treatment intensity cannot really be made. Although usage per patient in Northern Ireland appears higher than elsewhere in the UK, no reasonable comparison can be made given that only eight patients with haemophilia B are treated in the province and there is considerable interpersonal variation in clinical phenotype for this condition.


Page | 54

Table 12 Products issued to treat haemophilia B (including inhibitors), 2017/18

2016/17 2017/18

Biotest Haemonine ‐ 46,000

BPL Replenine 2,548,450 910,985

IDELVION 1,030,500 5,938,750

Mononine 362,000 78,000

Grifols Alphanine 5,876,000 4,748,000

Novo Nordisk NovoSeven (mg) 10,391 9,197

Pfizer BeneFIX 77,093,592 53,637,050

FEIBA 1,652,000 1,818,000

RIXUBIS 223,000 985,000

SOBI/Biogen ALPROLIX 3,303,013 12,136,054

Various Manufacturers Investigational Factor IX 2,420,676 260,074

CSL Behring

Manufacturer Product Total Units

Shire

Units in IU unless otherwise stated

Table 12: This gives a breakdown of the products issued to treat haemophilia B in the UK in 2016/17 and 2017/18, organised by supplier. These figures have been cross-checked with sales figures provided by the suppliers. Whilst we would not expect a perfect match between manufacture's sales figures and NHD usage figures, there was a high level of correlation except for low-usage products. Sales figures are not reported for reasons of confidentiality.

Note the continued marked reduction in the proportion of investigational factor IX use as clinical trials come to an end. We have deliberately aggregated and anonymised investigational products to avoid any breach of confidentiality agreements and to take account of commercial sensitivities. We are unable to distinguish between standard and extended half-life investigational products for that reason. We would advise that data on trial products should be shared at a local level with commissioners so that they have a realistic estimate of future product consumption and avoid any inadvertent reduction in future budget. A significant proportion of FIX used was plasma-derived, mainly for patients who do not “get on with” BeneFIX. The proportions of plasma-derived FIX supplied by BPL, CSL and Grifols have all declined, with patients switching to EHL FIX.

Tab

le 1

3 F

acto

r IX

uni

ts is

sued

by

UK

hae

mop

hilia

cen

tres

, by

diag

nosi

s, 2

017/

18

Plasma

Recombina

ntInve

stigationa

lEn

hanced

Half‐

Life

Total

Hae

mop

hilia

B688

5,782,985

54,622,050

260,074

18,074,804

78,739,913

Unclassified blee

ding

disorde

r1

‐

1,500

‐

‐

1,500

Total

68

9 5

,782,985

54,623,550

260,074

18,074,804

78,741,413

FIX (IU

)Co

agulation De

fect

Patie

nts

Trea

ted

Tabl

e 13

: T

his

show

s U

K f

acto

r IX

issu

ed in

201

7/18

, br

oken

dow

n by

pro

duct

typ

e an

d di

agno

sis.

N

ote

that

thi

s in

clud

es t

he u

se o

f ov

er

260,

000

units

of i

nves

tigat

iona

l rec

ombi

nant

fact

or IX

. T

his

repr

esen

ts a

sm

alle

r pro

port

ion

of th

e to

tal F

IX u

nits

issu

ed c

ompa

red

to la

st y

ear.

* P

oten

tially

ano

mal

ous

use

of fa

ctor

IX in

Tab

le 1

3 is

acc

ount

ed fo

r as

follo

ws:

Unc

lass

ified

ble

edin

g di

sord

er: P

atie

nt h

as s

ince

bee

n re

-reg

iste

red

as h

aem

ophi

lia B

and

will

be

repo

rted

as

such

in th

e ne

xt r

epor

t.

Page | 55


Figu

re 1

7 M

arke

t Sha

re o

f fac

tor I

X c

once

ntra

tes

issu

ed b

y U

K h

aem

ophi

lia c

entre

s, 2

017/

18

Figu

re 1

9 Th

is s

how

s th

e m

arke

t bre

akdo

wn

of fa

ctor

IX c

once

ntra

tes.

| egaP 65


Man

uact

urer

-Pro

duct

Typ

ePa

tient

s(n

)

Biot

est -

Pla

sma

1BP

L - P

lasm

a5

CSL B

ehrin

g - P

lasm

a2

CSL B

ehrin

g - E

nhan

ced

Half-

Life

73Gr

ifols

- Pl

asm

a19

Pfize

r - R

ecom

bina

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ire -

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mbi

nant

9SO

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Half-

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110

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s�ga�o

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nt F

IX10

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l78

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Pfize

r -Re

com

bina

nt68

.12%

Shir

e -R

ecom

bina

nt1.

25%

Gri

fols

-Pl

asm

a6.

03%

BPL -

Plas

ma

0.06

%

CSL

Behr

ing -

Plas

ma

1.16

%

Biot

est -

Plas

ma

0.10

%

SOBI

/Bio

gen

-En

hanc

ed H

alf-L

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nced

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alf-L

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Page | 57

2.3 Von Willebrand Disease

Tab

le 1

4 P

atie

nts

with

von

Will

ebra

nd d

isea

se r

egis

tere

d an

d tr

eate

d A

pril

2017

- M

arch

201

8

<10

10 ‐ 2

9 ≥30

N/K

Sub

To

tal

<10

10 ‐ 2

9 ≥30

N/K

Sub

To

tal

Type 1

25173

268

11477

80362

632

921,166

1,643

7534

Type 2A

3834

60

7896

7336

3208

286

695

Type 2B

69

50

2015

3515

267

8722

1Type 2M

179

30

2927

3510

375

104

183

Type 2N

10

30

43

223

432

365

0Type 2 Unspecified

58

50

1812

149

136

549

0Type 3

2661

8764

0Type Unreported

59132

234

7432

159

328

594

531,134

1,566

8933

Low VWF

01

200

210

039

039

600

0

Sub To

tal M

ales

3,923

351

76

Type 1

24121

197

4346

128

600

1,704

188

2,620

2,966

111

97Type 2A

2629

120

67120

110

664

300

367

7613

Type 2B

79

80

2414

4640

1101

125

260

Type 2M

923

40

3650

7018

4142

178

298

Type 2N

01

30

45

961

479

8314

0Type 2 Unspecified

44

10

918

2716

162

7111

1Type 3

1954

7346

0Type Unreported

59134

197

7397

210

610

1,553

150

2,523

2,920

129

73Low VWF

00

130

130

079

079

920

1Su

b To

tal Fem

ales

6,875

442

1

93

Grand

Total ‐ Males and

Fem

ales

10,798

793

2

69

2661

1954

Treated

with

De

smop

ressin

Fem

ales

Males

von

Willeb

rand

disease

<18 yea

rs

≥18 yea

rs

Total

Treated

with

Co

ncen

trate

VWD Ac

tivity

IU/dl

Page | 58



Page | 59

Table 14: This shows patients registered with von Willebrand disease broken down by age, activity level, subtype, gender and treatment. The Annual Report review meeting suggested that, whilst there is no generally agreed severity classification for VWD, we report subdivisions from <10, 10-29 and ≥30% VW activity to give some indication of the distribution of severity amongst the UK cohort.

A VW subtype is reported for 58% of patients, almost the same proportion as last year. Efforts are ongoing to tidy up this part of the database, but problems include repeatedly changing classification over time; very old data entries; and changing opinion in relation to the diagnosis of mild type 1 VWD, which may have been over-diagnosed in the past.

There remains an excess of blood group O patients and adult females, reflecting referral bias and possible over-diagnosis of mild type 1 VWD.

Table 15 (overleaf): This shows that 442 new patients with von Willebrand disease were registered in the past year, only 17% of whom were registered without indicating a subtype.

As one would expect, the previously reported relative excess of female registrants only becomes apparent after menarche. New registrations of von Willebrand disease are approximately equally distributed between genders in patients under 18 years of age.

Tab

le 1

5 N

ew R

egis

trat

ions

of v

on W

illeb

rand

dis

ease

bet

wee

n A

pril

2017

& M

arch

201

8, b

y ag

e at

mid

-yea

r, s

ever

ity, a

nd

gend

er

<10

10 ‐ 2

9 ≥30

N/K

Sub

To

tal

<10

10 ‐ 2

9 ≥30

N/K

Sub

To

tal

Type 1

425

391

691

1624

041

110

Type 2A

33

00

61

12

04

10Type 2B

10

10

20

00

00

2Type 2M

00

00

01

40

05

5Type 2N

10

00

10

00

00

1Type 2 Unspecified

02

10

31

01

02

5Type 3

10

1Type Unreported

14

100

151

45

010

25Low VWF

00

20

20

02

02

4

Sub To

tal M

ales

163

Type 1

026

261

533

4176

1121

174

Type 2A

14

20

71

65

012

19Type 2B

03

00

30

11

02

5Type 2M

12

00

30

20

02

5Type 2N

00

20

20

06

06

8Type 2 Unspecified

13

10

50

00

00

5Type 3

32

5Type Unreported

35

60

144

1317

135

49Low VWF

00

20

20

07

07

9

Sub To

tal Fem

ales

279

Grand

Total ‐ Males and

Fem

ales

442

32

Males

Fem

ales

von

Willeb

rand

disease

VWF Ac

tivity

IU/dl

Total

<18 yea

rs

≥18 yea

rs

10

Page | 60


0100

200

300

400

500

600

700

800

900

0510152025

Pa�ents (n)

Units(millions)

Tim

e Pe

riod

Plas

ma

Reco

mbi

nant

Pa�e

nts t

reat

ed

Figu

re 1

8 Fa

ctor

VIII

uni

ts is

sued

by

UK

hae

mop

hilia

cen

tres

to tr

eat V

on W

illeb

rand

dis

ease

199

3 – 2

017/

18

In

clud

es p

rodu

cts

cont

aini

ng a

com

bina

tion

of V

WF

and

FVIII

, whi

ch a

re re

porte

d in

FV

III u

nits

Figu

re 1

8: I

n co

ntra

st to

hae

mop

hilia

A a

nd B

, the

incr

easi

ng c

onsu

mpt

ion

of V

W C

once

ntra

tes

sinc

e 19

93 c

lose

ly r

efle

cts

the

incr

easi

ng

num

ber o

f pat

ient

s re

quiri

ng tr

eatm

ent.

The

num

ber o

f pat

ient

s w

ith T

ype

3 V

WD

has

incr

ease

d m

arke

dly

with

the

pass

age

of ti

me.

| egaP 36 | egaP 16



Page | 62

Table 16 Products issued to treat von Willebrand disease (including inhibitors), 2017/18

2016/17 2017/18

Bayer Kogenate 90,500 13,000

Haemate P 4,387,950 1,673,503

Riastap (g) ‐ 1,000

Voncento 9,118,900 13,002,900

Grifols Alphanate 873,000 494,000

LFB Biomedicaments Willfact /Wilfactin 1,027,000 1,458,000

Novo Nordisk NovoSeven (mg) 1,087 232

Wilate 5,417,904 6,884,000

Octaplex ‐ 1,015

Pfizer ReFacto AF 5,500 12,000

Shire Advate 35,000 182,000

Desmopressin 14,043 15,530

Investigational rVWF * *

Product Total Units

CSL Behring

Manufacturer

Octapharma

*Anonymised for confidentiality purposes Units in IU unless otherwise stated

Products containing VWF and FVIII are reported in FVIII units

Table 16: This shows a breakdown of concentrates issued to treat von Willebrand disease in the UK ordered by supplier. These are generally listed by and priced by their labelled factor VIII content, with the exception of Willfact VWF concentrate (LFB), which is labelled and priced only by its VWF content.

* Potentially anomalous product use in Table 16 is accounted for as follows:

Advate: Allergic to VWF products Advate: Developed an inhibitor Advate: Issued for low FVIII before confirmation of diagnosis Kogenate: Does not respond to typical VW products ReFacto AF: centre confirmed usage ReFacto AF: Entered in error, now corrected


Page | 63

2.4 Inhibitors: Congenital and Acquired

Tab

le 1

7 In

hibi

tors

by

dise

ase

seve

rity

– hae

mop

hilia

A, h

aem

ophi

lia B

& v

on W

illeb

rand

dis

ease

< 1

2,014

16(0.8)

150(7.4)

297(14.7)

463(23.0)

1 ‐ 5

818

4(0.5)

31(3.8)

48(5.9)

83(10.1)

>55,327

3(0.1)

15(0.3)

37(0.7)

55(1.0)

Total

8,159

23(0.3)

196(2.4)

382(4.7)

601(7.4)

Seve

re360

0(0.0)

11(3.1)

6(1.7)

17(4.7)

Non

‐Sev

ere

1,435

0(0.0)

0(0.0)

0(0.0)

0(0.0)

Total

1,795

0(0.0)

11(0.6)

6(0.3)

17(0.9)

Type

14,609

0(0.0)

0(0.0)

1(0.0)

1(0.0)

Type

3160

0(0.0)

6(3.8)

1(0.6)

7(4.4)

Others

6,030

0(0.0)

0(0.0)

0(0.0)

0(0.0)

Total

10,799

0(0.0)

6(0.1)

2(0.0)

8(0.1)

Coagulation De

fect

Seve

rity (

IU/dl)

/ Sub

type

Hae

mop

hilia

A

Hae

mop

hilia

B

Von

Willeb

rand

disea

se

In Reg

ister *

Inhibitors n (%

)

Newly

Repo

rted

Ongo

ing

Historica

lTo

tal

*

Incl

udin

g pa

tient

s no

t reg

ular

ly tr

eate

d N

ew=n

ewly

repo

rted

in y

ear

Ong

oing

=inh

ibito

r in

year

but

not

new

in y

ear

His

toric

al=h

isto

ry o

f inh

ibito

r, b

ut n

ot c

urre

nt

Page | 64



Page | 65

Table 17: This table shows the incidence of new inhibitors in the past year, the prevalence of inhibitors ever registered and the prevalence of those still considered active for haemophilia A, B and von Willebrand disease, broken down by disease severity.

Those labelled “new” were reported for the first time in the year 2017/18. Those labelled “ongoing” are those reported in previous years which have not been eradicated and which remain clinically significant. Those reported as “historical” are those reported to have been eradicated or disappeared and not ongoing.

This shows that an history of inhibitor is over twice as prevalent in severe than in moderate haemophilia A and twenty times more prevalent than in mild haemophilia A. The proportion of patients with non-severe haemophilia A, thought to have eliminated their inhibitor cannot be known with certainty, however, since some may have an undetectable inhibitor which may reappear as soon as they have factor VIII replacement. Similarly, many “ex inhibitor” patients with severe haemophilia probably continue to have some low-level inhibitor activity, below the level of detection of the Bethesda assay.

Inhibitors in haemophilia B are, fortunately, far less common, with a prevalence of 0.9% of patients registered with haemophilia B. These arise early in the patient’s treatment history and only in severe haemophilia B.

Inhibitors in von Willebrand disease appear in our cohort mainly in type 3 VWD and judged by the very low number of historical inhibitors reported (1 of 7), are very difficult to eradicate.

Table 18 (overleaf): Shows reported product use for UK patients with a current inhibitor during 2017/18, broken down by diagnosis and supplier. All product usage for these patients in that year is shown.


Page | 66

Table 18 Products issued to patients with congenital bleeding disorders reported to have a positive inhibitor during 2017/18

Bayer Kogenate 1,024,000 4

FVIII 8Y 127,590 1

Optivate 3,469,220 4

Helixate Nexgen 1,355,250 3

Riastap (mg) 6 1

Grifols Fanhdi 1,567,040 8

NovoSeven (mg) 18,642 91

NovoEight 151,000 4

Nuwiq 3,805,250 6

Octanate 3,281,500 6

Pfizer ReFacto AF 13,205,681 37

Roche Emicizumab (EAMS) 13,881 17

Advate 16,208,500 41

FEIBA 30,181,596 81

SOBI/Biogen Elocta 2,953,000 13

Desmopressin 94 2

Investigational FVII 3 1

Investigational FVIII mimetic 25,895 11

Investigational FVIII 451,466 5


Shire FEIBA 1,818,000 4

Haemate P 76,000 1

Voncento 386,300 4

Novo Nordisk NovoSeven (mg) 214 4

Shire Advate 137,000 1




Roche Emicizumab (EAMS) 900 1

Shire FEIBA 1,408,000 2

Desmopressin 30 1

CSL Behring

F.VII deficiency

Co‐inherited diagnoses

Various Manufacturers

von Willebrand Disease

F.XI deficiency

Manufacturer Product

Haemophilia B

Haemophilia A

Shire

BPL

Units Patients

CSL Behring

Novo Nordisk

Octapharma


Page | 67

Table 19 Products issued to patients with Acquired Inhibitors 2017/18

ManufacturerProduct /

Patients (n)Acquired

Haemophilia AAcquired

von WillebrandsAcquired

Deficiency ‐ Other

Bayer FVIII 8Y (n= 1) 4,000 ‐ ‐

Haemate P (n= 4) ‐ 75,500 ‐

Riastap (g) (n= 2) 2,006 ‐ ‐

Voncento (n= 19) 3,600 753,500 ‐

Novo Nordisk NovoSeven (mg) (n= 25) 5,634 ‐ ‐

Octaplex (n= 1) 2,000 ‐ ‐

Wilate (n= 13) ‐ 151,500 ‐

Pfizer ReFacto AF (n= 6) 14,000 3,000 ‐

Advate (n= 4) 56,000 ‐ ‐

FEIBA (n= 80) 7,797,500 ‐ ‐

Desmopressin (n= 3) 15 144 30

CSL Behring

Octapharma

Shire

Units in IU unless otherwise stated

Table 19: This shows reported product use for UK patients with an acquired inhibitor reported or ongoing during 2017/18, broken down by diagnosis and supplier.


Page | 68

Table 20 FEIBA® usage: breakdown by diagnosis

Coagulation DefectNumber of Patients

Total(u)

Haemophilia A 84 30,234,596

Haemophilia B 4 1,818,000

F.V deficiency 1 64,000

Acquired Haemophilia A 80 7,797,500

Co‐inherited diagnoses 2 1,408,000

Total 171 41,322,096

Table 21 NovoSeven® usage: breakdown by diagnosis

Coagulation DefectNumber of Patients

Total(mg)

Haemophilia A 92 18,649

Haemophilia B 10 9,197

von Willebrand disease 6 232

Acquired Haemophilia A 25 5,634

F.V deficiency 1 18

F.VII deficiency 64 3,206

F.XI Deficiency 2 124

Co‐inherited diagnoses 2 126

Bernard Soulier 10 185

Glanzmann's Thrombasthenia 46 5,457

Platelet defects 2 40

Unclassified bleeding disorder 2 20

262 42,888

Tables 20 & 21: These show in greater detail how much FEIBA® and NovoSeven® were issued for each diagnosis in 2017/18. Patients with any hereditary or acquired bleeding disorder, either with or without inhibitors, are included. There is no estimate given for off-label usage or usage for reversal of over-anticoagulation, for which we do not have data.


Page | 69

2.5 Rarer Bleeding Disorders


Page | 70

Table 22 Patients with rarer types of bleeding disorders registered and treated April 2017 & March 2018

Total Males Females Any

Product Concen‐trate

Desmo‐pressin

Probable von Willebrand disease 228 58 170 14 1 13 6.1

Platelet‐type Pseudo von Willebrand Disease 34 15 19 2 2 0 5.9

F.V deficiency 218 85 133 3 2 0 1.4

F.VII deficiency 1,420 680 740 67 65 0 4.7

F.X deficiency 266 115 151 35 22 0 13.2

F.XI Deficiency 3,274 1,354 1,920 71 48 0 2.2

F.XIII Deficiency 71 40 31 59 59 0 83.1

Combined II+VII+IX+X Deficiency 3 1 2 0 0 0 0.0

Combined V+VIII Deficiency 27 12 15 11 11 1 40.7

Co‐inherited diagnoses 306 151 155 31 27 6 10.1

Prothrombin Deficiency 13 5 8 3 3 0 23.1

Afibrinogenemia 16 9 7 14 13 0 87.5

Dysfibrinogenemia 532 215 317 19 19 0 3.6

Hypofibrinogenemia 155 67 88 7 7 0 4.5

Hypodysfibrinogenemia 33 16 17 2 2 0 6.1

Fibrinogen Deficiency 16 8 8 1 1 0 6.3

Acquired Haemophilia A 525 274 251 95 91 1 18.1

Acquired Haemophilia B 1 1 0 0 0 0 0.0

Acquired von Willebrands 134 73 61 35 34 1 26.1

Acquired Prothrombin Deficiency 7 4 3 0 0 0 0.0

Acquired F.XIII Deficiency 1 0 1 0 0 0 0.0

Acquired F.V Deficiency 5 0 5 0 0 0 0.0

Acquired Deficiency (other) 11 8 3 1 0 1 9.1

Glanzmann's Thrombasthenia 141 63 78 50 46 4 35.5

Bernard Soulier 92 44 48 12 10 1 13.0

Other platelet defects 2,685 823 1,862 108 2 89 4.0

Miscellaneous 275 72 203 16 5 10 5.8

Unclassified bleeding disorder 588 81 507 37 4 31 6.3

Haemophilia A with Liver Transplant 10 10 0 0 0 0 0.0

Haemophilia B with Liver Transplant 2 2 0 0 0 0 0.0

Total 11,089 4,286 6,803 693 474 158 6.2

Treated with Coagulation Defect

Number of Patients in Register %

Treated

Table 22 This shows patients registered with rarer disorders and the proportion treated during the year. It is suspected that liver transplantation is under-reported.


Page | 71

Table 23 Patients with selected rarer bleeding disorders registered and treated April 2017 – March 2018, by disease severity

In Reg Treated In Reg Treated In Reg Treated In Reg Treated

F.V deficiency 46 2 172 1 0 0 218 3

F.VII deficiency 130 26 1287 40 3 1 1420 67

F.X deficiency 41 28 225 7 0 0 266 35

F.XI Deficiency 245 28 3027 43 2 0 3274 71

Total 462 84 4,711 91 5 1 5,178 176

Coagulation Defect

Number of Patients (factor level IU/dl)

<5 ≥5 N/K Total

Table 23: It is acknowledged that these rarer disorders have no recognised classification of disease severity. However, the table above gives an idea of the range of registered levels.


Page | 72

Table 24 New registrations of rarer bleeding disorders between April 2017 & March 2018 showing their coagulation defect and gender

Coagulation Defect Male Female Total

Platelet‐type Pseudo von Willebrand Disease 1 6 7

Probable von Willebrand disease 6 27 33

F.V deficiency 5 10 15

F.VII deficiency 77 94 171

F.X deficiency 8 12 20

F.XI Deficiency 114 187 301

F.XIII Deficiency 2 2 4

Combined V+VIII Deficiency 0 1 1

Co‐inherited diagnoses 13 9 22

Afibrinogenemia 1 1 2

Dysfibrinogenemia 27 21 48

Hypofibrinogenemia 12 14 26

Hypodysfibrinogenemia 3 2 5

Acquired Haemophilia A 62 41 103

Acquired F.V deficiency 0 1 1

Acquired Prothrombin Deficiency 0 1 1

Acquired von Willebrand disease 7 8 15

Acquired Deficiency (other) 2 2 4

Glanzmann's Thrombasthenia 6 4 10

Bernard Soulier 1 4 5

Other platelet defects 84 219 303

Miscellaneous 5 19 24

Unclassified bleeding disorder 20 105 125

Total 456 790 1,246

Table 24: This table shows new registrations during the year. As usual, this continues to show a consistent excess of female registrations for all autosomal disorders, presumably reflecting referral and diagnostic bias of women with menorrhagia.

Tab

le 2

5 C

once

ntra

tes

used

to tr

eat r

arer

ble

edin

g di

sord

ers

betw

een

Apr

il 20

17 &

Mar

ch 2

018

Pts

trea

ted

Units

Pts

trea

ted

Units

Pts

trea

ted

Units

Pts

trea

ted

Units

Pts

trea

ted

Units

COAGADEX

‐ ‐ ‐ ‐ 5 338,470

‐ ‐ ‐ ‐

FXI

‐ ‐ ‐ ‐ ‐ ‐ 35

147,733 ‐ ‐

Beriplex

‐ ‐ ‐ ‐ 13

716,500

‐ ‐ ‐ ‐

Fibrogammin P

‐ ‐ ‐ ‐ ‐ ‐ ‐ ‐ 58

868,750

FXIII

‐ ‐ ‐ ‐ ‐ ‐ 2 3,572 ‐ ‐

LFB Biomedicam

ents

Hemoleve

n ‐ ‐ ‐ ‐ ‐ ‐ 13

137,000 ‐ ‐

Novo

Seve

n (mg)

1 18

64

3,206 ‐ ‐ 2 124 ‐ ‐

Novo

Thirteen

‐ ‐ ‐ ‐ ‐ ‐ ‐ ‐ 1 32,500

Octap

las (units)

2 1,710 ‐ ‐ ‐ ‐ 16

1,309 ‐ ‐

Octap

lex

‐ ‐ ‐ ‐ 18

1,179,500

‐ ‐ ‐ ‐

Advate

1 39,000

1 1,250 ‐ ‐ ‐ ‐ ‐ ‐

FEIBA

1 64,000

‐ ‐ ‐ ‐ ‐ ‐ ‐ ‐

FVII

‐ ‐ 2 268,800 ‐ ‐ ‐ ‐ ‐ ‐

Shire

BPL

CSL Behring

Octap

harma

F.XIII De

ficiency

Novo

Nordisk

Man

ufacturer

Prod

uct

F.V de

ficiency

F.VII d

eficiency

F.X de

ficiency

F.XI Deficiency

Uni

ts in

IU u

nles

s ot

herw

ise

stat

ed

Tabl

e 25

: T

his

give

s a

brea

kdow

n of

pro

duct

use

dur

ing

2017

/18

for

UK

pat

ient

s w

ith r

arer

ble

edin

g di

sord

ers,

bro

ken

dow

n by

dia

gnos

is

and

supp

lier.

Page | 73



Page | 74

2.6 Adverse Events


Page | 75

Table 26 Adverse Events reported between April 2017 & March 2018

Adverse EventNumber of Patients

Number of Events

Allergy Event 8 8

Infection Event 1 1

Inhibitor Event 23 23

Intracranial Haemorrhage 6 6

Malignancy Event 18 18

Other Event 8 9

Poor Efficacy Event 0 0

Thrombotic Event 10 10

Total 74 75

See table 17 for breakdown of inhibitors by disease severity in haemophilia A, B and von Willebrand disease


Page | 76

2.7 Morbidity and Mortality

Tab

le 2

7 C

ause

s of

dea

th in

pat

ient

s w

ith h

aem

ophi

lia A

and

B b

etw

een

Apr

il 20

17 &

Mar

ch 2

018

< 1

1 ‐ 5

>5 & <40

≥ 40

Unk

nown

Total

< 1

1 ‐ 5

>5 & <40

≥ 40

Unk

nown

Total

AIDS

00

00

00

01

00

01

ARDS

01

00

01

00

00

00

Carcinoma

24

71

115

00

10

01

Cerebral h

aemorrhage

10

30

04

00

00

00

COAD

00

10

01

00

00

00

Hae

morrhage (Misc)

20

00

02

00

00

00

Hepatocellular Carcinoma

00

10

01

00

00

00

Infection (Bacterial)

00

51

06

00

00

00

Ischae

mic Heart Disease

20

60

08

00

00

00

Pan

creatitis

00

01

01

00

00

00

Renal Failure

10

00

01

10

00

01

Ruptured Aorta (Peripheral

vascular disease)

00

00

00

00

10

01

Stroke

(Unkn

own)

01

00

01

00

00

00

Suicide

10

00

01

00

00

00

Unkn

own

35

244

036

11

40

06

Totals

1211

477

178

22

60

010

Haem

ophilia

AHa

emop

hilia

B

Cause of Dea

thSe

verity (factor V

III le

vel IU/dl)

Seve

rity (factor IX leve

l IU/dl)

Tabl

es 2

7 &

28:

T

hese

sho

w t

he c

ause

s of

dea

th a

mon

gst

patie

nts

with

hae

mop

hilia

A a

nd B

(in

clud

ing

carr

iers

), b

roke

n do

wn

by s

ever

ity

(Tab

le 2

7) a

nd f

or o

ther

ble

edin

g di

sord

ers

(Tab

le 2

8) d

urin

g 20

17/1

8.

At

pres

ent,

it ca

n be

asc

erta

ined

who

has

die

d fr

om t

he N

HS

spi

ne

but o

ur o

nly

sour

ce o

f cau

se o

f dea

th d

ata

is fr

om h

aem

ophi

lia c

entr

es th

emse

lves

. A

ll ca

uses

of d

eath

sho

uld

be r

epor

ted

to th

e da

taba

se,

whe

re th

is is

kno

wn.

Page | 77



Page | 78

Table 28 Causes of death in other coagulation defects between April 2017 & March 2018

Coagulation Defect Cause of Death Total

F.V deficiency Unknown 2

Haemorrhage (Misc) 1

Unknown 9

F.X deficiency Unknown 1

Accident 1

Carcinoma 2

Infection (Bacterial) 1

Ischaemic Heart Disease 1

Ruptured Aorta (Peripheral vascular disease) 1

Unknown 26

Co‐inherited diagnoses Unknown 1

AIDS 1

Aortic stenosis 1

Carcinoma 2

Cerebral haemorrhage 1

COAD 1

Haemorrhage (misc) 2


Ischaemic Heart Disease 7

Pancreatitis 1

Renal Failure 1

Senility/Alzheimer's disease 1

Stroke (thrombotic) 1

Unknown 55

Acquired F.V deficiency Unknown 1

Carcinoma 1

Unknown 6

Carcinoma 1


Renal Failure 1

Unknown 1

Hypofibrinogenemia Unknown 2

Prothrombin Deficiency Unknown 1

Carcinoma 2

Senility/Alzheimer's disease 1

Unknown 13

Miscellaneous COAD 1

Unclassified bleeding disorder Unknown 5

AIDS 1

Carcinoma 4

Cerebral haemorrhage 1

COAD 1

Haemorrhage (Misc) 1

Hepatocellular Carcinoma 2


Liver Failure 2

Stroke (Unknown) 1

Unknown 31

Total 219

Platelet defects

von Willebrand disease

Acquired von Willebrand Disease

F.XI Deficiency

F.VII deficiency

Acquired Haemophilia A

Dysfibrinogenemia


Page | 79

Figure 19 Cumulative incidence chart of deaths from hepatocellular carcinoma or liver failure in UK patients with bleeding disorders 1969 - 2017

0

50

100

150

200

250

300

Cumulative Pa

tient Dea

ths

Year of death

HepatocellularCarcinoma

Liver Failure Total

YearHepatocellular Carcinoma

Liver Failure

Total YearHepatocellular Carcinoma

Liver Failure

Total

1969 0 2 2 1996 0 10 10

1970 0 2 2 1997 0 10 10

1972 0 2 2 1998 0 9 9

1973 0 1 1 1999 0 4 4

1974 0 1 1 2000 0 15 15

1975 0 1 1 2001 1 6 7

1979 0 2 2 2002 3 9 12

1980 0 1 1 2003 2 2 4

1983 0 2 2 2004 3 4 7

1984 0 3 3 2005 1 2 3

1985 0 4 4 2006 4 5 9

1986 0 7 7 2007 2 3 5

1987 0 5 5 2008 3 6 9

1988 1 2 3 2009 2 8 10

1989 0 5 5 2010 2 9 11

1990 0 4 4 2011 2 5 7

1991 0 9 9 2012 3 8 11

1992 0 9 9 2013 9 9 18

1993 0 15 15 2014 0 4 4

1994 0 13 13 2015 2 9 11

1995 0 7 7 2016 0 2 2

2017 0 2 2

Total 40 238 278


Page | 80

Figure 19: This shows deaths directly attributable to liver disease. Bear in mind that most patients with bleeding disorders who die, do not die from liver disease.

Overall figures for deaths amongst bleeding disorders have been repeatedly misquoted in the media suggesting that all deaths are caused by HCV. This is not the case. The above table documents the number whose death certificate listed liver disease as the principal cause of death. Liver disease may have been a subsidiary contributory factor in other deaths but was not listed as the primary cause on the death certificate.

This appears to show some levelling-off of deaths from hepatocellular carcinoma (HCC) and from hepatocellular failure. This may be a reporting artefact in that we have not received death certification data from NHS Digital for two years, although we also collect reports of death directly from the haemophilia centres. However, as HCV is eradicated from a higher and higher proportion of patients, one would expect a reduction in the incidence of HCC, which declines dramatically after viral eradication, even in the presence of ongoing cirrhosis. There may be a delay before we see a reduction in deaths from hepatocellular failure, since some patients do have advanced cirrhosis with hepatocellular failure and not all are suitable for transplant or have a donor. However, successful viral eradication will result in complete recovery for patients with early cirrhosis or less advanced liver disease and they should not go on to develop advanced cirrhosis or die from complications of HCV.


Page | 81

Table 29 Summary of patients ‘at risk’ of vCJD for public health purposes who received UK sourced plasma products as reported by centres

Implicated batches

Non‐implicated batches

Combined

Alive 674 2525 3199

Dead 136 692 828

Total 810 3217 4027

MM ‐ ‐ 5

MV ‐ ‐ 4

VV ‐ ‐ 1

Not known 810 3217

M 770 2640 3410

F 40 577 617

0‐19 0 6 6

20‐39 303 771 1074

40‐59 267 1025 1292

60‐79 100 608 708

80+ 4 113 117

Not known 0 2 2

Sex

Current age band of living

‘at risk’ patients

Summary table of ‘at risk’ bleeding disorder patients who received UK sourced plasma products

Current status of ‘at risk’

patients

Genotype

These data were last updated on 30/06/2018

Table 29: This report is sent to Public Health England on a bi-annual basis. No patients with bleeding disorders have ever developed vCJD.


Page | 82

Figure 20 Total number of patients with haemophilia A, haemophilia B or von Willebrand disease treated by UK haemophilia centres

0

2

4

6

8

10

12Num

ber o

f Cen

tres

Number of treated patients

Figure 21 Total number of patients with severe haemophilia A and haemophilia B treated by UK haemophilia centres

0

2

4

6

8

10

12

14

16

18

20

Num

ber o

f Cen

tres

Number of treated patients

N.B: haemophilia A includes: Carrier of haemophilia A and females with FVIII deficiency Haemophilia B includes: Carrier of haemophilia B, females with FIX deficiency, FIX Leyden and FIX Leyden carriers


Page | 83

Appendix 2: Participating Centres

Aberdeen Leicester

Abergavenny Lewisham

Bangor Lincoln

Barnstaple Liverpool (R. I.)

Belfast ‐ Adult's Liverpool Children's

Belfast ‐ Children's Manchester (Adults)

Birmingham (Queen Elizabeth) Manchester Children's

Birmingham Children's Newcastle upon Tyne

Bournemouth / Poole North Hampshire (Basingstoke)

Bradford North Staffordshire (Stoke on Trent)

Brighton Norwich

Bristol (Infirmary & Children's) Nottingham

Cambridge Oxford

Canterbury Peterborough

Cardiff Plymouth

Chichester Portsmouth

Coventry Royal Free

Derby Salisbury

Dundee Sheffield (Children's)

Edinburgh Sheffield (Royal Hallamshire)

Exeter Shrewsbury

Glasgow (R.H.S.C.) Southampton

Glasgow (R.I.) St George's Hospital, London

Great Ormond Street St Thomas' and Guy's Hospital

Hammersmith Hospital, London Swansea

Inverness Taunton / Yeovil

Ipswich The Royal London Hospital

Kettering Torquay

Kingston upon Hull (Hull) Truro

Lancaster Wolverhampton

Leeds York

Centre Name


Page | 84

3. Haemtrack Annual Report 2017 Introduction

This report is reported by calendar year rather than by financial year since 10% of the data is reported on paper, after a delay.

Haemtrack is used by patients to report home therapy to their haemophilia centre and so its use is not limited to haemophilia A or B but includes other, rarer, bleeding disorders for which patients also use home therapy. Both haemophilia centres and patients vary in their reporting compliance with Haemtrack and so the quality of individual patient self-reported data varies and the proportion of patients using the system also varies from centre to centre. In general, data quality is improving and the proportion of patients using the system is increasing.

Our aim is that Haemtrack should become a routine part of home-therapy management and a valuable tool for the review and optimisation of home-therapy and for patient education. For that to happen, compliance will have to improve and be reinforced by Health Care Professionals (HCP’s) reviewing Haemtrack records with patients in clinic and checking the data for accuracy before downloading into HCIS, where it should be checked by HCPs prior to uploading into the National Haemophilia Database.

Haemtrack should also be used in multidisciplinary team meetings (MDTs). Many haemophilia centres already do this and in those centres recruitment and data quality are steadily improving. This requires a consistent investment in time by the centre staff which results in improving compliance with both home therapy and record keeping.

Some haemophilia centres appear not to have realised the full clinical utility of this reporting system and consequently return sub-optimal data, which may reflect some degree of non-engagement by both HCPs and their patients. It is important to demonstrate to the patient, by referring to Haemtrack data on screen in clinics, that collecting and reporting treatment data is useful for their clinical management, and that it’s collection is not just an empty bureaucratic exercise.

NHS funding has come under extreme pressure and NHS England, desiring responsible use of drugs and accountability, have made it clear that compliant use of Haemtrack will be a prerequisite for access to more expensive new treatments such as Hemlibra® and EHL-IX. NHS England require hard proof that these drugs are cost effective in normal use and that they improve outcome.

For that reason, it is necessary to be able to demonstrate that the use of resources is being closely monitored and the way in which these resources are used can be accounted for. Patient-reported data, such as Haemtrack, is an important element of this and so it is important that centres take steps to obtain more complete data from a higher proportion of their patients. This may require significant effort and may also have staffing implications at a centre level, which will have to be addressed but which could be funded from the CQUIN budget or as part of the forthcoming service review.


Page | 85

Section 1: Patients’ Haemtrack Usage Analysis 1.1 Overall

Figure 1 presents an overview of severe and moderate patients with haemophilia A or haemophilia B using Haemtrack from 2008 to 2017. The blue columns give the numbers of patients that on Haemtrack and the lines show the proportion of NHD patients who use Haemtrack. This illustrates rapid growth in 2012, when recruitment was the subject of a CQUIN. Figure 1 also reveals that there has been a gradual rise in the rate of recruitment, especially in severe haemophilia A cohort.

Figure 1 Number of patients using Haemtrack and recruitment rate, 2008-2017


Page | 86

1.2 Haemtrack usage analysis at centre level - patients with severe Haemophilia

Use of Haemtrack has increased at a rapid rate in recent years and most Comprehensive Care Centres (CCCs) use Haemtrack to some degree, though far fewer Haemophilia Centres (HCs). This may relate to staffing issues and perhaps a lower degree of engagement in HCs who may only have a few patients suitable for the system.

Figures 2 and 3 display the proportion of patients with severe haemophilia A/B using Haemtrack in each CCC (Figure 2) and HC (Figure 3). Recruitment is a little better in CCCs than in HCs.


Page | 87

Figure 2 Comparison of recruitment to Haemtrack by centre for patients with severe haemophil ia A: Comprehensive Care Centres (CCCs) in 2017

Figure 3 Comparison of recruitment to Haemtrack by centre for patients with severe haemophil ia A: Haemophil ia Centres (HCs) in 2017


Page | 88

Compliance with record keeping amongst patients using Haemtrack also varied considerably. For the purposes of this report, compliance refers to the patient’s annual product usage reported through Haemtrack as a proportion of the factor issued to the patient, as reported quarterly to the NHD. Good compliance has been arbitrarily defined as Haemtrack reporting of use of >75%.

Figure 4 and 5 exhibit the overall compliance by patients for CCCs and HCs respectively. The compliance value closer to 100 indicates better usage compliance. The figures show the mean (diamond), median (vertical line), interquartile range (bar) and range (whiskers) compliance.

The median compliance in patients with severe haemophilia A from CCCs and HCs in 2017 are 89% and 90% respectively. This shows that, although fewer HCs use Haemtrack than CCCs, the quality of reporting is similar. In 2016, the median values of compliance for CCCs and HCs are 78% and 80% respectively.

Compliance has improved considerably in recent years, both in CCCs and HCs, and is generally quite good.

Figure 4 Overall compliance in patients with severe haemophil ia A, by Comprehensive Care Centre


Page | 89

Figure 5 Overall compliance in patients with severe haemophil ia A, by Haemophil ia Centre


Page | 90

Section 2: Patients’ Reporting Analysis

2.1 Patients’ Reporting Medium

Figure 6 shows the proportion of Haemtrack users using different reporting methods between 2011 and 2017. This shows an initial rapid uptake of the use of the web application at the expense of paper reporting. Subsequently, when the iPhone and then the Android app were introduced, they rapidly gained popularity at the expense of the web application. Oddly, the use of paper has remained stable over the past several years. This is curious given that electronic data can be very quickly quality-checked and rapidly imported into the haemophilia Centre Information System (HCIS) whereas paper records need to be laboriously keyed in by centre personnel. Most centres have a small proportion of patients using paper, but some centres still have most of their patients reporting on paper even though this creates more work for centre staff. The number of patients who are statistical outliers for compliance and use a paper reporting system suggests that some of these records had been manually entered by centres without checking or reconciliation. More recently, there seems to be a considerable increased in checking at centre level since there are far fewer obvious errors.

Figure 6 Change in the use of different Haemtrack Reporting Media: 2011- 2017

This is further analysed in Figure 7, which breaks down the interval between treatment and reporting by the reporting method used (smartphone apps, web and paper). Use of phone apps is associated with the most rapid reporting, with almost 40% of data being recorded on the day of treatment and a further 30% within a week. In contrast, only 18% of treatments were


Page | 91

reported the same day and a further 25% within a week using web. Most data submitted on paper was reported after an interval of up to 3 months, either by post or at the next review clinic. Data reported by phone app was returned after a median of only 2 days, whereas paper-recorded data was reported after a median of 54 days with the web being intermediate. There is no difference in the median age of patients using phone app and web, while the patients using paper are older than those two groups, the median age being 24, 24 and 31 years for phone app, web and paper reporters, respectively.

We are actively promoting the use of the iPhone and Android apps in preference to other methods of reporting because we believe that the data are not only available to centres more quickly but are likely to be more accurate.

Haemtrack 2 has been launched during the course of the year and patients are slowly changing to this. Being completely web-based, it may be used on any smartphone and will synch automatically but is dependent on having a Wi-Fi connection. This version is also easier to use.

We will have extended the use of Haemtrack to inpatient use (data entered by centre staff) so that it will provide a complete treatment record.

Figure 7 Haemtrack Reporting Delay by Reporting Medium 2017


Page | 92

Figure 8 Reporting compliance by reporting medium, ranked by median compliance 2017 (CCC’s) in patients with severe haemophil ia A

Figure 8 exhibits box and whisker plots of compliance broken down by reporting medium used for patients with severe haemophilia A from CCCs. Boxes show the 25th to 75th percentiles; whiskers the arithmetic range. The vertical black line shows the median and the diamond shows the mean.

It is clear that electronic reporting methods returned better compliance than paper form. In 2017, the number of patients using only phone apps is 564 and those using web only is 342. Eighty-two patients continue to “prefer” paper. The number of patients choosing to use two reporting mediums was 216 and 9 patients used three mediums. All combinations of electronic reporting showed similar levels of compliance. This may be selection bias. Those using phone apps were, by and large, using web before. The patients using more than one medium to report their treatments may have changed their reporting medium in the year.


Page | 93

4. Data Management Working Party

Membership

Chair: Professor Peter Collins

Commissioner representative: Will Horsley Director(s) of the National Haemophilia Database: Professor Charles Hay Data Managers’ Forum representative: Lynne Dewhurst Haemophilia Nurses Association representative: Emma Franklin Haemophilia Physiotherapists Group representative: David Stephenson Haemophilia Society representative: Liz Carroll MDSAS representative: Dr Rob Hollingsworth Patient representative: Barry Flynn Representatives of Northern Ireland, Scotland and Wales: Northern Ireland Dr Gary Benson Scotland Dr Elizabeth Chalmers Wales Professor Peter Collins UKHCDO Working Party Chairs: Co-morbidities Working Party Dr Rhona Maclean Genetics Working Party Dr Keith Gomez Inhibitor Working Party Dr Dan Hart Musculoskeletal Working Party Dr Pratima Chowdary Paediatric Working Party Dr Elizabeth Chalmers Peer Review Working Party Dr John Hanley Von Willebrand Working Party Prof Mike Laffan UKHCDO Executive Committee: Chair Dr Ri Liesner Secretary Dr Kate Talks (Other execs listed above) Members of the NHD as nominated by the Director(s) of the National Haemophilia Database: Working Party Secretary Lynne Dewhurst Bruce Cowen Ben Palmer Dr Hua Xiang Meetings

The UKHCDO Data Management Working Party (DMWP) met on 11th May 2018 (Manchester) and 28th Sept 2018 (London). The terms of reference for the Working Party are available on the UKHCDO website.


Page | 94

The DMWP oversees all aspects of data collection and analysis of patients with inherited bleeding disorders undertaken by the National Haemophilia Database (NHD). The DMWP and NHD are jointly responsible for the accuracy and completeness of the data collected. The DMWP has delegated most of the responsibility for assessing and overseeing requests for analysis of NHD data to the Data Analysis Group (DAG) which is a subcommittee of the DMWP.

The DMWP regularly reviews the information that is collected on patients and revises this as necessary. Any member of UKHCDO can suggest changes to the data that are collected and these will be considered by the DMWP. At present the way that platelet disorders are recorded is being updated.

All members of UKHCDO are encouraged to suggest data analyses to the DMWP and DAG, this can be done by individual members or through UKHCDO Working Parties.

Examples of ongoing UKHCDO projects supported by NHD are:

The Acquired Haemophilia A registry Immune Tolerance Induction registry Enhanced half-life factor VIII and IX registry Mortality in severe haemophilia

The DMWP and NHD are ensuring that the Infected Blood Inquiry has full access to the information held by the NHD along with any help in the interpretation of that data that is required by the Inquiry.

Haemtrack

The Haemtrack system continues to expand with more patients registered and more treatments recorded. Commissioners for England and the devolved countries of the UK encourage the use of Haemtrack as a means of capturing individual patient events and treatment. This has allowed important information about the impact of enhanced half-life factor VIII and IX to be collated. The introduction of Emicizumab will be closely observed with particular focus on any thrombotic events.

Haemtrack Video Consultation – Haemtrack has the ability for clinicians to hold patient video consultations within the Haemtrack system. This can be accessed through “clive.mdsas.com”

IT update

Centres can now record on HCIS whether a patient is taking prophylaxis and what the prescribed regimen is.

It is planned that the database will be re-written over the next few years to ensure ongoing functionality. This will be a major undertaking jointly performed by NHD and MDSAS.

NHD aims to link with the WAPPS-Hemo (www.WAPPS-HEMO.org) population pharmacokinetics programme run by McMaster University. This link will allow centres to input 2-3 factor VIII or factor IX levels and receive an interactive read out that allows levels to be predicted at any time after an infusion. In addition, the effect of potential prophylactic regimens can be explored with patients to better optimise treatment. The system has the advantage that all concentrates, including enhanced half-life factor VIII and IX, can be used.

UKHCDO would like to thank many individuals involved in the work of the NHD. Professor Hay is the clinical Director of NHD and oversees its function on a day to day basis on behalf of UKHCDO.


Page | 95

The following people work for the National Haemophilia Database and have been invaluable in their very high-quality work collecting and analysing the data on our behalf.

Katie Allen Helen Brown Bruce Cowen Lynne Dewhurst Rachel Lockwood Ben Palmer Sarah Rooney Tom Sharpe Hua Xiang

We also thank Rob Hollingsworth and MDSAS for their continued support and maintenance of our national information systems.

We also wish to acknowledge all the important work done at the centre level and for the support of all the patients for supporting this important work.

Prof Peter Collins, Chair UKHCDO Data Management Working Party

Prof Charles RM Hay, Director NHD

September 2018


Page | 96

5. Data Analysis Group

Membership

Co-Chair (Chair of Data Management Working Party) Professor Peter Collins

Co-Chair (Director of NHD) Professor Charles Hay

User representatives: Dr Ryan Cheal Paul Sartain

UKHCDO members: Dr Elizabeth Chalmers Dr Pratima Chowdary Dr Dan Hart Dr Ri Liesner

Haemophilia Nurses and Physiotherapy representatives: Simon Fletcher David Stephenson

National Haemophilia Database: Bruce Cowen Lynne Dewhurst Ben Palmer Dr Martin Scott (observer) Dr Hua Xiang

Meetings

The Data Analysis Group (DAG) is a subgroup of the Data Management Working Party. Its role is to assess and prioritise applications to analyse data held by NHD, including Haemtrack and joint score data. Applications are assessed based on data governance considerations, scientific merit and available resources. The group meets once a month by teleconference which last on average 60-90 mins. The DAG has met every month since April 2017. The terms of reference of the DAG are available on the UKHCDO website.

Requests for analyses are submitted on a standardised form. This form is available from NHD.

The DAG reviews and discusses all applications. It provides feedback to the applicant and works with them to refine the proposal, if necessary. The contributions from the user representatives have been particularly useful in assessing the applications.

The data analyses that are generated from the requests are reviewed and commented on by the group and may be further revised, if necessary, before release.

The DAG is developing an investigator-led proposal to Roche/Chugai to analyse data held on the NHD relating to the introduction of Emicizumab.

Requests for data analyses have been submitted by individual members of UKHCDO, UKHCDO working parties, NHS England, NHS Wales and pharmaceutical companies.


Page | 97

All members of UKHCDO and UKHCDO working parties are encouraged to suggest analyses and are invited to collaborate with the DAG on these projects. The DAG is open to new members from UKHCDO and anyone interested should contact Charlie Hay and Peter Collins.

Prof Peter Collins, Chair UKHCDO Data Management Working Party

Prof Charles RM Hay, Director NHD

September 2018


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6. Co-Morbidities Working Party

Membership

Chair Rhona Maclean

UKHCDO representatives: Gary Benson, Belfast Bella Madan Guys and St Thomas’ Mike Makris, Sheffield Gillian Evans, Canterbury Susie Shapiro, Oxford Sarah Mangles, Basingstoke Gerry Dolan, Guys and St Thomas Jason Coppell, Exeter

Haemophilia Nurses Association Representative: Cathy Harrison, Sheffield

Haemophilia Physiotherapist’s Group Representative: Fionnuala Sayers, Belfast

The terms of reference for this working party were agreed in September 2018.

Lines of Responsibility

The Co-Morbidities Working Party (CMWP) is responsible to the UKHCDO Executive and Advisory Committees.

The UKHCDO Executive and Advisory Committees approve the terms of reference and approve the remit of the CMWP

The chair of the CMWP – or representative- will participate in the UKHCDO Data Management Working Party (DMWP).

Remit

To consider comorbidity issues in patients with bleeding disorders within the UK and review any unmet need with respect to data collection, guidelines and patient related information / material.

To develop a Work Plan for the CMWP.

To advise the DMWP as to what data the NHD should collect regarding comorbidities in patients with haemophilia and bleeding disorders.

Any publications arising from the CMWP should be approved by the UKHCDO Executive in line with the UKHCDO publication policy.


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7. Genetics Working Party

Membership

Keith Gomez Chair Nicola Curry Gerry Dolan Steve Keeney Representing Genetics Laboratory Network Mike Laffan Megan Sutherland Representing Genetics Laboratory Network

Remit

1. Continue role as oversight committee for issues related to genetics in haemophilia 2. Annual guideline review 3. Support ThromboGenomics programme and enrolment of patients in NIHR UK

Biobanking initiative 4. Support genetic analysis of all patients with inherited bleeding disorders and for results

to be recorded on NHD 5. Provide oversight of gene therapy trials for haemophilia in the UK

Meetings and work streams

The working party met by teleconference in October 2017 and September 2018.

The working party has produced a new good practice paper entitled Recommendations for the clinical interpretation of genetic variants and presentation of results to patients with inherited bleeding disorders. This has been submitted for publication.

The provision of genetic testing services in England has been revised by NHS England with a consolidation of services into four hubs. We are currently in the transition period and over the next year, the testing of samples will be transferred to the hubs. There should not be any break in service provision, but for many members the testing laboratory will change. On behalf of UKHCDO the Genetics Working Party responded to the NHS England stakeholder consultation regarding potential issues regarding the quality of genetic reporting. We have been used to a service tailored to the needs of UK haemophilia clinicians and the working party will monitor the service to assess how this is maintained.

The ThromboGenomics platform continues to be the main platform providing testing for genes in rare bleeding and platelet disorders. The long-term provision of this service is unclear following the NHS England service reconfiguration, but the current plan is for it to continue perhaps with a testing fee. Genomics England 100K project is due to close later this year and it is not clear whether a similar testing platform will be introduced to replace it.

There are now 11 centres enrolling patients into the NIHR rare diseases project. As of June 2018, 869 patients had been enrolled including 340 from Liverpool and 236 from Oxford.


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A proposal for revising the registration of heritable platelet disorders has been submitted to the Data Management Working Party. This should allow capture of the genetic variants and other phenotypic features.

The table below shows the capture of genetic diagnosis for haemophilia A and B as of end of April 2018. There is regional variability in submission of data with some examples of incomplete submission. This is partly due to staffing issues in laboratories and will be monitored by the Genetics Laboratory Network.

Number of patients with a genetic diagnosis by region (based on patient's postcode and not registered centre)

Patients registered with the NHD 2017/18 Haemophilia A includes females with VIII deficiency & haemophilia A carriers Haemophilia B includes females with IX deficiency, haemophilia B carriers, FIX Leyden & FIX Leyden carriers

Dr K Gomez, Chair, Genetics Working Party

September 2018

< 1 1 & 5 > 5 40+ N/K

East Midlands 72 (41.9%) 11 (16.7%) 65 (20.8%) 10 (7.4%) 1 (10.0%)

East of England 28 (19.7%) 7 (8.0%) 39 (9.8%) 4 (2.7%) 0 (0.0%)

London 95 (27.5%) 22 (29.3%) 81 (19.2%) 9 (5.9%) 0 (0.0%)

North East 12 (17.4%) 8 (21.1%) 36 (29.3%) 20 (16.8%) 0 (0.0%)

North West 55 (26.8%) 28 (31.5%) 92 (25.1%) 23 (16.7%) 1 (20.0%)

Northern Ireland 43 (58.9%) 18 (60.0%) 66 (45.2%) 0 (0.0%) 0 (0.0%)

Scotland East 7 (8.4%) 4 (11.1%) 17 (10.0%) 0 (0.0%) 0 (0.0%)

Scotland West 2 (3.0%) 2 (6.3%) 3 (2.3%) 3 (2.5%) 0 (0.0%)

South East 99 (31.0%) 29 (36.7%) 82 (14.3%) 20 (11.2%) 0 (0.0%)

South West 33 (23.1%) 3 (4.4%) 19 (5.7%) 5 (7.7%) 0 (0.0%)

Wales 32 (39.0%) 9 (26.5%) 34 (18.7%) 4 (9.3%) 0 (0.0%)

West Midlands 37 (21.5%) 3 (5.1%) 15 (6.1%) 1 (1.0%) 0 (0.0%)

Yorkshire and the Humber 18 (12.2%) 4 (3.4%) 20 (5.5%) 8 (6.3%) 0 (0.0%)

Total 533 (26.4%) 148 (18.3%) 569 (15.1%) 107 (7.3%) 2 (2.8%)

East Midlands 7 (23.3%) 3 (14.3%) 4 (8.2%) 0 (0.0%) 0 (0.0%)

East of England 1 (2.6%) 2 (7.1%) 1 (1.2%) 0 (0.0%) 0 (0.0%)

London 4 (6.5%) 4 (7.1%) 8 (6.7%) 1 (2.2%) 0 (0.0%)

North East 2 (16.7%) 1 (9.1%) 1 (3.3%) 1 (3.6%) 0 (0.0%)

North West 8 (22.9%) 13 (35.1%) 14 (21.9%) 10 (21.7%) 0 (0.0%)

Northern Ireland 3 (33.3%) 1 (25.0%) 4 (23.5%) 0 (0.0%) 0 (0.0%)

Scotland East 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%)

Scotland West 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%)

South East 7 (11.5%) 8 (14.3%) 11 (10.4%) 3 (9.4%) 0 (0.0%)

South West 1 (5.6%) 2 (11.1%) 6 (9.2%) 0 (0.0%) 0 (0.0%)

Wales 3 (27.3%) 13 (56.5%) 9 (27.3%) 0 (0.0%) 0 (0.0%)

West Midlands 5 (16.1%) 6 (35.3%) 2 (3.0%) 0 (0.0%) 0 (0.0%)

Yorkshire and the Humber 2 (7.7%) 0 (0.0%) 3 (6.3%) 3 (13.0%) 0 (0.0%)

Total 43 (12.0%) 53 (15.7%) 63 (8.2%) 18 (5.8%) 0 (0.0%)

Haemophilia B

Factor VIII / IX level (iu/dl)

Patients with a genetic diagnosis (% of registered patients)

Haemophilia A

Diagnosis Region


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8. Genetic Laboratory Network Background

The UKHCDO GLN was formed in 2002, arising out of the UKHCDO Genetic Working Party (UKHCDO GWP), with the aim of improving collaboration between laboratories and of ensuring quality and equity of service across the U.K. The network currently comprises 13 laboratories, 12 across the UK plus Dublin, involved in the molecular genetic analysis of haemophilia and related inherited bleeding disorders (many of the laboratories are also involved in other areas as well).

Representatives of the Network attend meetings of the UK Genetic Testing Network (UKGTN) and the UKHCDO GWP.

Meetings

The UKHCDO GLN holds bi-annual meetings and met on 21 November 2017 in London and 17 May 2018 in Cambridge. The next meeting is scheduled for November 2018 in Nottingham.

Chair & Secretary

Megan Sutherland and Catriona Keenan continue in their roles as Chair and Secretary, respectively.

Current activities

1. NHS England genetic laboratory re-designation exercise. During the current year the Genomics Laboratory Hub tendering process has been conducted by NHS England and a test directory has been produced which specifies services required to be delivered under the new service model in England, including bleeding disorders. Four entities have been selected to deliver this new service model and planning/implementation is underway. This represents a major change in bleeding disorder service configuration within England.

2. Laboratory Audit – ISO 15189: Laboratories in the Network are accredited by, or undergoing inspection for accreditation by, the United Kingdom Accreditation Service. Laboratories are required to adhere to ISO 15189 quality standards. The GLN continues to share examples of good practice, practical advice and knowledge as the inspection process is applied to member laboratories. The Network has implemented an informal sample exchange scheme between members of the GLN for disorders that are not provided for by UK NEQAS. The majority of laboratories have now successfully undergone the UKAS inspection process with the surveillance visit process now underway.

3. National Haemophilia Database (NHD) Genetics Portal: The NHD Genetics Portal allows members of the GLN to upload genetic variant data for patients they have investigated into the patient’s record on the NHD. The Genetics Portal is used by members of the GLN to see if a variant they have found has been reported by other centres, thereby providing evidence for pathogenicity calculations of genetic variation. During these searches the patient details are not shown. Members are also able to


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search for patients to confirm which centre they are registered at, and if a genetic variant has been reported prior to contact for release of relevant details if appropriate (no further information regarding the variant is made available).

4. Bleeding Disorder Genetic Analysis Best Practice Guidelines: The VWD genetic analysis guideline will be reviewed in accordance with the genetic test directory recently produced by NHS England and associated changes in service re-alignment (see item 1). Recent advances in the classification of genetic variation will also be considered and implemented in the guideline. The BPGs for Haemophilia A and Haemophilia B will also require review along similar lines once the new format has been created for the VWD guidelines.

5. Genetics of Heritable Bleeding Disorders NEQAS scheme: The Genetics of Heritable Bleeding Disorders EQA scheme, run by UK NEQAS in Sheffield, continues with bi-annual distributions. The results for each round of the scheme are reviewed and discussed at the following network meeting and any relevant comments fed back to the steering group. The scheme currently includes F8, F9 and VWF gene analysis. The GLN have discussed the need for further disorders to be included in the scope of the EQA scheme, in line with the published genetic test directory.

6. Participation in other groups: Representatives of the Network input to the UKHCDO GWP.

7. General: The GLN has discussed the application of next generation sequencing (NGS) approaches and traditional Sanger sequencing methods. GLN members who are currently using NGS analyse panels of genes and filter results according to the clinical indication. With the recent publication of the genetic test directory, analytical approaches to the investigation of heritable bleeding disorders will include both Sanger sequencing and NGS.

Megan Sutherland, Chair, UKHCDO Genetic Laboratory Network

October 2018


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9. Inhibitor Working Party

Membership

Dr Dan Hart Chair Dr Kate Talks Secretary Dr Elizabeth Chalmers Prof Peter Collins Dr Georgina Hall Prof Charlie Hay Dr Ri Liesner Prof Mike Makris Ben Palmer Dr Charles Percy Dr Anne Riddell

The Inhibitor Working Party (IWP) has been reconstituted and welcomed new membership. We have met twice face to face, a third time via a comprehensive teleconference call and multiple ad hoc communications to address the important issues emerging in this rapidly changing field.

IWP members led or contributed to clinical policy development for both recombinant porcine FVIII (susoctocog alpha, Obizur®, Shire) and biphenotypic FVIII-mimic antibody (Emicizumab, Hemlibra®, Roche). These have both now been NHS England approved for acquired haemophilia A (AHA) and congenital haemophilia A with inhibitors respectively and also adopted in devolved nations. Our laboratory survey and subsequent updates for the availability of the product specific assays identified the initial variation in availability of assays between centres, but importantly provided a document for centres’ labs to identify which neighbouring laboratories could perform these urgently if needed. Our laboratory specific email cascade has facilitated direct communication between NHD and lab chiefs and between labs in this key time of rapid change.

Obizur use in AHA has been included in the continuing national prospective data collection in AHA. This prospective data collection has entered its 3rd year and collected data on treatment and 12 months outcomes for over 300 AHA patients.

The launch of the early access scheme for Emicizumab in January 2018 required rapid generation of national guidance to treat bleeds in the presence of Emicizumab. These guidelines have been openly accessible via the Haemophilia journal since early in the year and remain a key reference document for treaters internationally. Our ongoing prospective collection of ITI outcome data is now integrating Emicizumab use as we continue to understand how to position this molecule in routine clinical care. Future NHD data will be crucial to inform this ongoing debate about the importance of long-term tolerance to FVIII. IWP members have had multiple discussions with various stakeholders to safeguard control and oversight of emerging data, whilst looking to find ways of working productively with other registries, either as product specific registries (e.g. Emicizumab) or in the European Medicines Agency future registries initiative.


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IWP and NHD team members have endeavoured to ensure clarification and rapid communication to the membership of any product specific adverse events and intend to launch an NHD, Emicizumab-specific prospective data collection (analogous to the AHA system) at the annual general meeting.

The past year has seen unprecedented change in the field of inhibitor therapeutics, laboratory monitoring and treatment algorithms. I am very grateful to the entire IWP membership who have all contributed to a much more fluid and demanding need than ever before to respond to events as they have emerged. Also, on behalf of the IWP membership, we would like to express our gratitude to all centres for their ongoing data returning for the multiple initiatives.

Dr D Hart Chair, Inhibitor Working Party

October 2018


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10. Laboratory Working Party

Agreed Process and Membership

Applications from UKHCDO members were invited by e mail and reviewed by UKHCDO exec. Membership to be reviewed on a 3-yearly basis

Group must compose of clinicians who treat haemophilia and Biomedical and Clinical Scientists who are involved in laboratory testing of patients with haemophilia

TTP and thrombophilia would not be covered in this working group – the specific focus is laboratory aspects of bleeding disorders, liaising with other working parties (e.g. inhibitor, VWD and rare bleeding disorders) when relevant

It was considered appropriate to have a maximum of 10 members

In addition, there will be a representative from NEQAS and NIBCS

Minutes are sent to the UKHCDO secretary

Meeting frequency to be determined by projects. At least once a year face to face

First meeting Monday 19th March 2018

Co-chairs

Dr Vincent Jenkins Laboratory Lead, Haemostasis and Thrombosis, University of Wales College of Medicine

Dr Will Lester Consultant Haematologist, Queen Elizabeth Hospital Birmingham

Working Party members and co-opted representatives from NEQAS and NIBSC:

Dr Steve Austin Consultant Haematologist, St George's Hospital London Dr Annette Bowyer Haemophilia Assays Section Lead, Royal Hallamshire Hospital

Sheffield Clive Burgess Haematology Laboratory Manager, Great Ormond Street Hospital for

Children London Dr Pratima Chowdary Consultant Haematologist, Royal Free Hospital London Dr Elaine Gray Principal Scientist representing National Institute for Biological

Standards and Control Dr Steve Kitchen Clinical Scientist representing NEQAS, Royal Hallamshire Hospital

Sheffield Paul Murphy Health Care Scientist, Royal Victoria Infirmary Newcastle Sean Platton Principal Biomedical Scientist , The Royal London Hospital Ms Anne Riddell Haemophilia Laboratory Manager, Royal Free Hospital London


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Remit

UKHCDO Lab Working Party Remit.

Current work streams

UKHCDO Guideline for laboratory monitoring of factor replacement therapy for patients with haemophilia A and B (chair EG) – Final draft Nov 18

UKHCDO Guidelines for laboratory measurements in haemophilia patients with inhibitors (chair VJ) – final draft Nov 18

Active list of specialist coagulation laboratories and test repertoires (chair AR)

Dr Vincent Jenkins & Dr Will Lester Co-Chairs, Laboratory Working Party

October 2018


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11. Musculoskeletal Working Party

Membership

Dr Pratima Chowdary Chair Dr Desmond Creagh Dr John Hanley Dr Angela McKernan Mr Peter Briggs Prof Simon Frostick Mr Nicholas Goddard Mr Paul McLaughlin Mr Stephen Classey Mrs Anna Wells Mrs Angela Westoby

Meetings

The Musculoskeletal Working Party (MSK) met once this year.

Activities/Plans

MSK working party this year has met once in person and by Teleconference on another occasion. Has had change in the Chair in the last year. Of the two guidelines the working party has agreed to author it was decided to prioritise the guideline related to standards of musculoskeletal care. As part of the work, the first round of Delphi consensus has been conducted and the second round will be completed later this year. Additional members have been invited to contribute to the first round of consensus. In addition, information on joint arthroplasty and synovectomy for patients are being reviewed.

Dr P Chowdary Chair, Musculoskeletal Working Party

October 2018


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12. Paediatric Working Party

Membership

Dr Elizabeth Chalmers Chair, Glasgow Dr Jeanette Payne Secretary, Sheffield Dr Jayanthi Alamelu London (Evelina) Dr Neha Bhatnagar Oxford Dr Tina Biss Newcastle Dr Mary Mathias London (GOSH) Dr Jayashree Motwani Birmingham Dr Mike Richards Leeds Dr Oliver Tunstall Bristol

The working party membership was renewed in October 2017.

Meetings

Two per annum with additional telecoms as required.

Last meeting: September 2018.

Summary of activities.

1. ITI Outcome data

• Retrospective follow up of Immune tolerance therapy in the UK (2003-2015)

Retrospective outcome data on the results of immune tolerance therapy in the UK (2003-2015 inclusive) has been collected from 8 UK CCCs treating children with inhibitors. Results of this analysis have been presented at the AGM previously & a manuscript is currently in preparation.

• Management & outcome of Immune tolerance using a standardised regimen (with inhibitor WP) - ongoing data collection in collaboration with IWP

A standard ITI protocol based on the current UKHCDO Guideline was agreed and commissioned previously. New inhibitors are reported to the NHD and prospective data collection on ITI outcomes has now been ongoing for almost 2 years. An update of the data collected so far will be presented at the AGM.

2. Intracranial haemorrhage in inherited bleeding disorders

Retrospective data collection (2003-2015) on cases of ICH occurring in children <16yrs of age in the UK has been completed and has been published in the journal Haemophilia. The data highlight the continuing risk of this complication in very young children with severe bleeding disorders. Prospectively data collection on ICH in both children and adults has been added to the NHD adverse events reporting scheme.


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The WP is also in the process of setting up a PUP registry via the NHD which will collect data on early exposure to FVIII and FIX in children with severe haemophilia. Data is also being collated in relation to the following areas:

• Inhibitors in Haemophilia B • Outcomes in moderate Haemophilia • Bleeding and treatment in children with rare coagulation disorders

The PWP also intends to pilot a national advisory group which will aim to act as a forum for advice on the management of children with inherited bleeding disorders. Further information on this will be circulated shortly.

Dr Elizabeth Chalmers Chair, Paediatric Working Party

October 2018


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13. Von Willebrand Working Party

Membership

Prof Mike Laffan Chair Dr Keith Gomez Dr Anne Goodeve Vince Jenkins Dr Will Lester Dr Carolyn Millar Dr Susie Shapiro Dr Henry Watson Dr Thynn Yee

The VWD working party was reformed in 2017 and the above membership agreed. The working party has not met since the last AGM.

Following the revised guidelines diagnostic categories and registration criteria there remains some work to complete on the revised registration form. This is ongoing with NHD.

A successful application was made to the Data Analysis Group for release of data which will allow the ‘Impact of revised classification on VWD registration in the UK’ to be assessed.

The 2014 guidelines will be reviewed in light of forthcoming ASH guidelines on diagnosis and management of VWD but do not require rewriting at present.

Prof Mike Laffan, Chair, Von Willebrand Working Party

October 2018


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14. Peer Review Working Party

Membership

Dr John Hanley Chair Dr Julia Anderson UKHCDO Member Dr Tina Biss UKHCDO Member Dr Gillian Evans UKHCDO Member Dr Lishel Horn UKHCDO Member Dr Ri Liesner UKHCDO Member Dr Rhona MacLean UKHCDO Member Dr Tim Nokes UKHCDO Member Anna Wells Lead Physio HCPA Sarah Bowman Social Worker Cathy Harrison Chair HNA Liz Carroll CEO Haemophilia Society Graham Knight Patient Representative Dr Kate Khair Past Chair HNA Dr Anne Yardumian Peer Review Programme Clinical Lead Rachael Blackburn Assistant Director WMQRS

As discussed and endorsed at the 2017 AGM, the Peer Review working party has continued a collaborative approach between the UKHCDO and the West Midlands Quality Review Service (WMQRS). Over the last 12 months the Working Party has met on several occasions.

The early part of the year focussed on finalising the Quality Standards for the care of Inherited and Acquired Bleeding Disorders. These were finalised and widely circulated.

WMQRS have coordinated the training for members of Peer review teams. 63 people have completed training and a further 36 are signed up for training.

The UK Peer Review programme will commence in November 2018. This will include visits to all Comprehensive Centres and several Haemophilia Centres. There will be 35 visits in total. Dates have been confirmed for 22 visits and 13 still to be confirmed.

The aim is to complete the programme of Peer Review visits over a 12-month period with the production of a summary report for the 2019 UKHCDO AGM. There will also be a Best practice sharing event in late 2019.

Dr John Hanley, Chair, Peer Review Working Party

October 2018


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15. Gynaecology Task Force

Membership

Dr Nikki Curry, Consultant Haematologist, Oxford Chair of writing committee

Dr Rezan Abdul-Kadir, Consultant Obstetrician and Gynaecologist, Royal Free Dr Louise Bowles, Consultant Haematologist, Royal London Professor Justin Clark, Consultant Obstetrician and Gynaecologist, Birmingham Dr Gill Lowe, Consultant Haematologist, Birmingham Dr Jason Mainwaring, Consultant Haematologist, Bournemouth Dr Sarah Mangles, Consultant Haematologist, Basingstoke Dr Bethan Myers, Consultant Haematologist, Leicester

The task force has met several times and have agreed the guideline structure and are awaiting the completion of the literature search to enable us to start writing the guideline. It will be a guideline that mirrors the UKHCDO obstetric guideline.

Dr Nikki Curry Chair, Gynaecology Task Force writing committee

October 2018


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16. Prophylaxis Task Force

Membership

Dr Rachel Rayment (adult) Co-Chair Dr Tina Biss (paediatric) Co-Chair Dr Steve Austin Dr Elizabeth Chalmers Kate Forsyth Dr Richard Gooding Dr Anne Kelly Dr Susie Shapiro Dr Kate Talks Dr Oliver Tunstall

The prophylaxis task force has met once in July 2017.

Remit of the group

This task force is in the process of revising and updating the UKHCDO/BSH guideline on the use of prophylactic factor concentrate in children and adults with haemophilia that was published in 2010.

The writing group are evaluating newer approaches to prophylaxis including the use of pharmacokinetic modelling, extended half-life products and novel molecules. The updated guidance will extend beyond severe haemophilia A to include guidance for individuals with non-severe haemophilia and haemophilia B. There will be a greater emphasis on prophylaxis use during adulthood including in adults with co-morbidities.

A literature search has been completed and the group aim to produce a first draft of the guideline by October 2018.

Dr Tina Biss, Co-Chair, Prophylaxis Task Force

September 2018


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17. Haemophilia Nurses’ Association

Membership

Cathy Harrison Chair Simon Fletcher Vice-Chair Shaun Emmitt Secretary Clare Forrester Sarah Johns April Jones Jenna Stanley Anne Wareing Dr Kate Khair (stepped down May 2018)

The Haemophilia Nurses Association (HNA) represents specialist nurses who care for people with bleeding disorders in the UK either through direct clinical practice or research. The last year has been exhilarating, and dominated by the WFH 2018 congress, held in May. HNA members participated in the treatment room and enjoyed meeting and treating people living with bleeding disorders from across the world and found collaborating with each other and with multidisciplinary peers a very rewarding experience.

As a consequence of WFH taking place in Glasgow, we chose not to run our annual conference in 2018, but instead convened a short AGM in the treatment room after the nurses’ day of the congress. We plan to hold a series of smaller, regional meetings throughout the autumn, giving us the opportunity to review topics presented at WFH, and to reassess the haemophilia nurse competency framework, which needs to be updated given the changing treatment landscape. The meetings will also focus on offering nurses peer review training. The new peer review process is due to start this Autumn/Winter and represents a vast change from the previous audit process. The review paper has been supported and developed with a multidisciplinary approach and represents a transparent review of the services provided by each centre. HNA members were involved in its development and are training and signing up to be reviewers with a good representation from across the UK.

The HNA was initially formed in the mid-1980s because nurses were experiencing the trauma of HIV/AIDS diagnoses and deaths. The HNA remains an organisation designed to support our members and provide forums for reflection and discussion. With the infected blood inquiry now underway, and at a time when staffing resources are tight across the UK, we recognise that our members are again working under stress. Therefore, in March 2019 we will again run a full annual conference, designed around a theme of wellbeing and resilience.

HNA meetings and courses are run by Haemnet, our education/research charity. In October 2017, the Contemporary Care of People with Bleeding Disorders course trained 16 participants from the UK and Ireland, and in October 2018 a cohort of 24 multidisciplinary professionals will head to Sheffield for the next course. This course is a unique, practical, hands-on educational opportunity developed and delivered by nurses and physiotherapists from key UK centres, supplemented by invited experts. It is the only course for nurses and physiotherapists specialising in the care of people with bleeding disorders.


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Also, in 2017 the ASPIRE clinical leadership development programme saw the second cohort of 6 nurses and allied care professionals from centres across the UK participate in three modules throughout the year. Other initiatives designed to enhance the level of practice and professionalism of nurses currently practising in the UK have included events designed to share experience with extended half-life products, and collaborative work on subcutaneous administration techniques. In addition, our members have participated in the Haemnet Horizons events, which facilitate collaborative work among nurses across Europe. We also have several on-going studies underway and hope shortly to begin collaborating with UKHCDO members on a study looking at pain.

We strongly believe that participation in our events greatly enhances the sense of community among HNA members and will go some way towards ensuring a happy, well-educated and sustainable haemophilia nurse establishment for the future. We recognise, however, that in recent years, many nurses have experienced difficulty in securing funding or study leave for educational courses and meetings. As a result, we have moved towards a model of centralised funding for our programmes, allowing us to keep the costs of attending courses down to a very low level, and where possible we make no charge at all; for some meetings we are also able to cover nurses’ travel costs, but we cannot do anything about study leave. We would strongly urge all centre directors to support their nurses in attending the educational opportunities that we are able to offer.

HNA members are key stakeholders in the ongoing care of people living with bleeding disorders; our members are playing an active role on new initiatives within the UK haemophilia treater community; including the CRG, CMU, the peer review group, and various UKHCDO working parties. The HNA committee wishes to thank all of the nurses who represent their colleagues on these groups. HNA members continue to bring passion to their roles, ensuring the national voice of haemophilia nursing is represented. Representation at Glasgow WFH 2018 showed the world what an amazing, passionate group of nurses we are. I am proud to be one of them.

Cathy Harrison, Chair, Haemophilia Nurses’ Association

September 2018


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18. Haemophilia Chartered Physiotherapists' Association

We aim to define, promote and encourage best practice for physiotherapy within haemophilia care, providing professional leadership and directing national physiotherapy policy.

Executive Committee

Anna Wells Chair: David Hopper Vice-Chair David Stephensen Research Lead Hannah Harbidge Secretary Joanne Minshall Treasurer

Research

Over the past 12 months HCPA members have continued to support and facilitate a thriving research and innovative environment. The annual meeting includes a half-day session focussed on sharing and developing research activity. As well as contributing joint score data to a multitude of observational and interventional studies, HCPA members have actively published and initiated several single and multi-centre musculoskeletal studies. Key papers published by the group this year include a thorough review of recent advances in musculoskeletal physiotherapy for haemophilia [Stephensen, Bladen & McLaughlin, Therapeutic Advances in Hematology; 2018; 9(8):227–237], and inter-rater reliability of physiotherapists performing the Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) protocol to evaluate synovitis and joint arthropathy [Stephensen, Classey, Harbidge, Patel, Taylor, Wells; Haemophilia; 2018; 24(3):471-476]. At the WFH Congress this year in Glasgow, three of the eight musculoskeletal abstracts selected for the free paper presentation session were submitted by UK physiotherapists. Hannah Harbidge presented a study evaluating the inter-rater variability of global gait score assessment using the HJHS criteria; Vishal Patel presented a paper reporting a novel physiotherapy-led musculoskeletal clinic for people with haemophilia and their perceptions of this clinic; and Steve Classey presented interim results of a real-world study on the use of point of care ultrasound imaging to guide treatment decision in people with haemophilia. Elizabeth Bradshaw will be presenting her work on measuring change following an acute bleed episode - what outcome measures do haemophilia patients think are of most value at the national Chartered Society of Physiotherapy 2018 congress. Based on this work, Elizabeth has secured funding from the NIHR Pre-doctoral Clinical Academic Fellowship scheme to develop a proposal to investigate the effectiveness of pulsed shortwave diathermy (PSWD) in the treatment of acute bleeds, with a view to conducting a trial researching home-based versus hospital based delivery.

NIHR Research Fellow, David Stephensen has led NIHR funding grants to investigate a feasibility study exploring the benefits of a muscle strengthening programme for children with haemophilia and a Novo Nordisk Access to Insight Clinical Research Grant to explore use of home ultrasound to empower the haemophilia patient to distinguish between bleeding and non-bleeding episodes. David Hopper will undertake a PhD linked to this work. Steve Classey has received a Pfizer Investigator Initiated Research grant to explore the use of point of care ultrasound imaging to guide treatment decision in people with haemophilia. Paul McLaughlin


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was successfully awarded a NIHR clinical doctoral research fellowship to complete a PhD in which he will investigate a rehabilitation intervention for the management of chronic arthritic joint pain in people with haemophilia. Paul McLaughlin in collaboration with Haemnet have received a Pfizer Investigator Initiated Research grant to bring together haemophilia professionals (nurses and physiotherapists) and personal trainers to develop a disease-specific fitness programme that can be delivered to young men with haemophilia to increase levels of participation in exercise and physical activity. Melanie Bladen was successfully awarded funding from the Sir William Coxen Trust to investigate the feasibility and sensitivity of using the i-STEP (an incremental step test standardised for height) to monitor physical function in boys with haemophilia.

An international collaboration led by the HCPA has been established to identify and standardise a core set of performance-based outcome measures of physical function in people with haemophilia (IPOP). The rationale for this work is based on the comprehensive evaluation and description of health recommendations of the World Health Organisation via the International Classification of Function (ICF) framework that suggest severity of health conditions are best described in terms of “Body Structures and Functions”, “Activities” and “Participation”. Activity reflects ability to perform daily tasks while participation reflects involvement in life situations. Current physical assessment of haemophilia focuses on joint structure, with little information on function or ability to perform and participate in activities. Furthermore, patients report little benefit from the HJHS in understanding their health. Standardising a core set of outcomes is necessary whilst minimising patient burden of multiple assessments. A consensus-based, decision analysis approach will be used to select the performance-based measures of physical function. This will be achieved through focus groups utilising Nominal Group Techniques as well as a series of online decision surveys.

In collaboration with the EAHAD Physiotherapy Committee, we have completed a survey of the role and scope of practice of haemophilia physiotherapists in Europe. This information will be used to establish principles of physiotherapy practice for people with haemophilia to support professional education strategies and self-governance of physiotherapists.

Anna Wells, Chair, Haemophilia Chartered Physiotherapists’ Association

September 2018


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19. BCSH Haemostasis and Thrombosis Task Force

Membership

Prof Mike Laffan Chair Dr Keith Gomez Secretary Dr Ian Jennings UK NEQAS representative Prof Isobel Walker UK NEQAS representative Dr Elaine Gray NIBSC representative Dr Raza Alikhan Dr Will Lester Dr Tina Biss Dr Deepa Arachillage Dr Julia Anderson UKHCDO representative Mr Sean Platton Mr Peter Baker

Professor Laffan and Dr Gomez continue for a second term as Chair and Secretary, respectively, from July 2018. The Task Force has met on 16th November 2017, 9th March 2018, 5th July 2018 and will meet on 20th October 2018 at the BSH Headquarters, London.

UKHCDO Guidelines Published 2017/2018

Hemlibra/ Emicizumab prescription and dosing: guidance from UKHCDO and NHSE. a UKHCDO Document, 2018.

Treatment of bleeding episodes in haemophilia A complicated by a factor VIII inhibitor in patients receiving Emicizumab. Interim guidance from UKHCDO Inhibitor Working Party and Executive Committee. PW Collins, R Liesner, M Makris, K Talks, P. Chowdary, E Chalmers, G Hall, A Riddell, C L Percy, C R Hay, D P Hart. Haemophilia 2018 24 344-347

Management of Inherited Bleeding Disorders in Pregnancy. S Pavord, B Madan, T Cumming, W Lester, E Chalmers, B Myers, H Maybury, C Tower, R Kadir. Green-top Guideline No. 71, published 27/04/17. https://www.rcog.org.uk/en/guidelines-research-services/guidelines/gtg71/

Guideline for the management of acute joint bleeds and chronic synovitis in haemophilia. J Hanley, A McKernan, M D Creagh (on behalf of the UKHCDO musculoskeletal working group). Haemophilia 2017 23 511-520.

UKHCDO protocol for the first line immune tolerance induction for children with severe haemophilia A: A protocol from the UKHCDO Inhibitor and Paediatric Working Parties. 01/02/17. P Collins, E Chalmers, J Alamelu et al. Haemophilia 2017 23 654-659

http://www.ukhcdo.org/wp-content/uploads/2017/01/ITI-protocol-2017.pdf


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BSH Guidelines Published 2017/2018

The use of viscoelastic haemostatic assays in the management of major bleeding. N S Curry, R Davenport, S Pavord, S V Mallett, D Kitchen, A A Klein, H Maybury, P W Collins, M Laffan. B J Haem 2018 182 (6) 789-806

Management of thrombotic and haemostatic issues in paediatric malignancy. K R Sibson, T T Biss, C L Furness, J D Grainger, R E Hough, C McCartney, J H Payne, E A Chalmers. B J Haem 2018 180 (4) 511-525

Guidelines in Preparation

The laboratory investigation of heritable disorders of platelet function. Andrew Mumford (chair), Keith Gomez, Tina Biss, Julia Anderson, Gill Lowe, Ian Jennings, Sean Platton, Peter Baker.

Prophylactic factor concentrate in children and adults with haemophilia A and B. Rachel Rayment and Tina Biss (co-chairs), Steve Austin, Liz Chalmers, Richard Gooding, Anne Kelly, Susie Shapiro, Kate Talks, Ollie Tunstall-Pedoe.

Laboratory aspects of assays used in haemostasis and thrombosis. Peter Baker (chair), Sean Patton, Ian Jennings, Paul Murphy, Elaine Gray, Claire Gibson, Mike Laffan. (Claire Gibson has joined the writing group representing BMS working in general haematology laboratories).

Recommendations for the clinical interpretation of genetic variants and presentation of results to patients with inherited bleeding disorders. A UK Haemophilia Centre Doctors' Organisation Good Practice Paper. K Gomez (chair), M Laffan, N Curry, P Lunt.

UKHCDO Guidelines Publications Policy

A UKHCDO Publication Policy has been written by Professor Makris and approved at the 57th Advisory Committee meeting on 7 September 2018. Any UKHCDO member or working party can propose a guideline title for approval by the Advisory Committee. Once the title is approved the member or working party decides on the membership of the group to produce the guideline and this is not restricted to UKHCDO members. Once the guideline has been completed it has to be approved by the UKHCDO Advisory committee before submission for publication. The title should include the fact that this is a UKHCDO guideline. The authorship should reflect the contributors to the guideline, provided they satisfy the international criteria for authorship. Membership of a working party does not mean automatic authorship on a guideline manuscript. It is recognised that not all UKHCDO Guidance will lend itself to the BSH guidelines process, but where possible it is preferable to have a guideline written and approved by BSH along with the mandatory audit template. Manuscripts that have followed the BSH process should be submitted to the British Journal of Haematology. Non-BSH approved guidelines, or those rejected by the British Journal of Haematology should be submitted to the Haemophilia journal. There is an agreement with both the British Journal of Haematology and the Haemophilia journal that all UKHCDO guidelines will be made freely available on publication. The UKHCDO website will link to the freely available manuscript as soon as it goes on line in early view at the


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journal website. Guidelines not intended for publication in a journal, as well as updates, will be published on the UKHCDO website and will be linked to the original guideline if one exists.

There are currently 20 UKHCDO guidelines and their status was discussed at the 55th Advisory Committee meeting on 19 January 2018. In accordance with the BSH process, each new guideline should incorporate an audit template. All current guidelines are reviewed against the BSH guidelines process which stipulates that those older than five years require formal review with a new literature search and consideration of updating or archiving. UKHCDO and BSH both fund literature searches. The 2005 publication titled: Framework for genetic service provision for haemophilia and other inherited bleeding disorders by CA Ludlam, KJ Pasi et al. has been archived, and the guidelines page updated in July 2018 to include the RCOG Greentop guideline No. 71.

Two Task Forces have been convened: the UKHCDO Gynaecology Task Force, chaired by Dr Nicky Curry, and the UKHCDO Laboratory Working Group, chaired by Dr Will Lester.

Dr Julia A M Anderson UKHCDO Representative for BSH Haemostasis & Thrombosis Task Force

September 2018


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20. Haemophilia Society WFH Congress 2018

Much of this year was dominated by preparations for hosting the World Federation of Hemophilia Congress in Glasgow from 20-24 May 2018. Congress was a huge success with 5110 delegates from 132 nations attending.

Newly Diagnosed Family Weekends

Hearing that your child has a bleeding disorder brings a huge range of emotions, for those who know they have a family history it often brings guilt for passing on the gene, or fear that your child will go through some of the devastating consequences your father or brothers experienced. For others the news is totally unexpected and comes along with questions about unexplained bruising. Social services involvement and fear for your baby and your family life. Our free weekends enable new parents to learn more about what to expect, meet others who are experiencing the same emotions and spend time hearing from and talking to experts helping them build a foundation of knowledge and support as they start their journey as a family. Specialist bleeding disorder physio’s, nurses, doctors, psychologists and social workers facilitate sessions alongside our local group representatives and youth ambassadors.

Youth Activities

This year we focussed our youth activities in summer camp in Surrey that reduced the isolation of living with a bleeding disorder, recognised the impact on siblings and raised confidence levels in our younger members.

From learning to give your treatment for the first time and understanding what your condition really means for you, to understanding how teamwork and determination can help you make huge leaps (literally in some cases), the campers loved every moment, even the torrential rain!

Youth Ambassador engagement

Our Youth Ambassadors are fundamental to our work, they attend many of our events and services, sharing their experiences, demonstrating treatment and offering a role model to younger members as well as reassurance to parents that a severe bleeding disorder won’t hold you back in life.

The first social for people aged 18-29, a trip to a comedy night in Leeds only attracted a few people but gave the foundations for the survey conducted slightly late to understand and increase youth involvement.

50 participants responded which the youth ambassadors used to evidence their request for funding for increased activity in 2018.

A youth ambassador also sits on the board now to regularly update the board on the work they have been doing.

Talking Red Programme

We began our Talking Red programme for women with bleeding disorders in 2014. This year almost 50 people came together at a weekend conference in Birmingham.

We discussed periods, surgery, nose bleeds and relationships. We shared an update on our first university Talking Red focus groups and the work of the EHC women’s committee.


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We also had a rallying cry from Talking Red ambassador Linda Wild, a social worker discussed support for women affected and held a breakout session for partners.

We had a stand at the fresher’s fair at University of Sheffield and had a footfall of 3,000 people.

Ageing

This year our aging project looked at how we could support our members with HIV and Hepatitis better, as well as focussing on staying well as you get older. Our conference looked at maintaining activity levels when you age, ensuring good dental health, as well as giving updates on new developments in HIV and Hep C treatment.

Inhibitor Project

We know that a diagnosis of an inhibitor takes a family from someone having a rare bleeding disorder that impacts daily life to an overwhelming situation where normal life seems far away and treatment, hospital trip and anxiety levels soar.

Our residential weekend in Leicester enabled 8 families of a child with an inhibitor and 3 adults with inhibitors to come together and hear from physiotherapists, psychologists and youth ambassadors as well as facilitated peer to peer sessions to share experiences and coping mechanisms. As members of the EHC inhibitors group we enabled one of our families to attend the European inhibitor summit. We also have a new inhibitor liaison rep who will be working with us to develop our services and advocacy as well as support other families with inhibitors.

Volunteering

We just couldn’t function without our incredible volunteers, Throughout the year over 30 healthcare professionals supported us at our events volunteering either for a day or an entire weekend, alongside hundreds of members who run our local groups and helped organise events across the country while youth ambassadors and talking red ambassadors have also volunteered at our events and educational days.

Advocacy

This year was dominate by our work focussed on access to new treatments for people with bleeding disorders. As members of the Clinical Reference Group in England (which is attended by Welsh and Scottish clinicians representatives too) we bring the collective patient voice along with two patients to provide advice to the decision makers in the NHS on what matters to our members about treatment, care and support. This included access to innovative new treatments, access to specialist nursing and physio care, and sharing people’s experiences at their haemophilia centres.

Public inquiry into infected blood

After so many years of campaigning, the community welcomed the announcement in July that there would be a full Statutory Public Inquiry. Our campaigning continued to ensure the responsibility for the Inquiry was removed from the Department of Health and Social Security and eventually this was changed to the Cabinet Office in late 2017.

The Trustee Board committed to funding of dedicated staff from a legacy, and subsequently a full-time position of Public Inquiry Lead was appointed and a dedicated Sub Committee of Trustees was formed to oversee the work on the Inquiry. A series of Roadshows was held with members around the UK to understand their expectations of the Inquiry and how they wanted to be represented by The Society.


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Sir Brian Langstaff was appointed as Inquiry Chair on the 8 February 2018. A consultation was opened on the Terms of Reference and using a range of channels, including a new social media group, we gathered opinions to inform our response to this Consultation.

Fundraising

Our fundraisers have continued to do amazing things for us this year, from hosting dinners to running marathons right through to abseiling down the Orbit Tower in the Olympic Park and golf days. We have also seen increased support from community groups such as the Freemasons (via donations and Ladies Nights). However, we are seeing a decline in people taking part in activities and hosting their own events. If we are to continue to provide the activities that we do, we hope to find new ways to engage with our community and the wider public and look to our members for new ideas and advice.

Liz Carroll, Chief Executive, The Haemophilia Society

October 2018


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21. Macfarlane Trust

As reported last year, in March 2017 the Minister announced that the NHS Business Services Authority (BSA) would take on the role of the new scheme administrator in England during 2017/18, along with similar organisations in the Devolved Administrations. At the time of writing last year’s report, it was expected that the transfer would take place on 1 November 2017; the transfer went ahead as anticipated on this date, and the majority of staff transferred to BSA under TUPE.

This meant that from 1 November 2017, the Department of Health (DH) ceased to fund the Macfarlane Trust to provide support to those with haemophilia who were infected with HIV as a result of contaminated blood products, and their families. However, as MFT has held reserves, the board decided to run two one-off grants programmes: one to provide grants for specialist equipment, and health-and mobility-related repairs and improvements to property, the other with the Honeycombe Memorial Fund to provide grants to bereaved partners and spouses to help them regain economic independence. Beneficiaries were invited to apply for grants in January 2018, with a closing date of 26 February 2018. The board then met at the end of March 2018 and agreed to award grants totalling approximately £450,000.

Once all of the grants have been paid to beneficiaries, and with no further funding being received for charitable activities, the board will need to consider a number of legacy issues, including when to wind up. This is likely to be by February 2018.

Jan Barlow, Chief Executive, The Macfarlane Trust

September 2018

ukhcdo annual report 2018 & bleeding disorder statistics ......ukhcdo annual report 2018 &...

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