HAEMOPHILIA B

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2 Haemophilia B

1803Philadelphia physician Dr John Conrad Otto recognised that the condition was hereditary and affected males

1944Argentinian physician Dr Alfredo Pavlosky was able to show that blood from one haemophiliac could correct the clotting problem in a second haemophiliac and vice versa

1952Recognition of haemophilia A and haemophilia B as two distinct diseases.In the same year, Stephen Christmas was discovered to be deficient in clotting factor IX and inspired the alternative term ‘Christmas disease’ for haemophilia B

1950s & early 1960s

Haemophilia B patients were treated with whole blood or fresh plasma infusions. However, there weren’t enough factor IX proteins in these blood products to stop serious internal bleeding

1960sThe clotting factors were identified and named. An article in Nature in 1964 described the clotting process in detail. Dr Judith Pool discovered cryoprecipitation

WHAT WE KNOW ABOUT HAEMOPHILIA

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1970sConcentrates containing factor VIII became available as freeze-dried powdered concentrates that could be kept at home and used as needed. This allowed people to travel, have jobs, and hope to live normal lives

1980sNew sterilisation techniques were introduced to combat viral safety concerns

1990sScientists discovered a way to make a ‘synthetic’ clotting factor IX concentrate (also known as ‘recombinant’ concentrate) without the need for human plasma. This improved the purity of the product and reduced safety concerns

1997The first recombinant clotting factor treatment for haemophilia B was launched in the UK

FUTURE APPROACHES Non-clotting-factors, some of which may one day offer the possibility of a long-term solution for people with bleeding disorders

2016The first extended half life clotting factor concentrate for haemophilia B was launched in the UK

4 Haemophilia B

Haemophilia is a relatively rare condition that causes bleeding problems. People with haemophilia do not bleed any faster than normal, but they can bleed for a longer time if they are injured, as their blood does not have enough clotting factor.

WHAT HAEMOPHILIA B IS

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HAEMOPHILIA IS QUITE RARE.

Affects 1 in every 5,000 malesApproximately 6,000 registered patients in the UKThey do not have enough clotting factor VIII

Haemophilia is a bleeding problem caused by reduced levels of clotting factor.The result is the same for haemophilia A and B patients. That is, they bleed for a longer time than normal.

In most cases haemophilia is inherited, meaning that it is passed from parent to child through the parent’s genes.

For those with haemophilia, the genes responsible for the production of clotting factors are altered, leaving the patient vulnerable to internal or external bleeding.

About one-third of cases are known as sporadic haemophilia, which arises even though there is no family history of it. In these instances, the gene has changed spontaneously.

Affects 1 in every 30,000 malesApproximately 1,200 registered patients in the UKThey do not have enough clotting factor IX

QUICK FACT

A BHAEMOPHILIA HAEMOPHILIA

6 Haemophilia B

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HOW HAEMOPHILIA B IS INHERITEDHaemophilia B is caused by a defect in one of the genes that determine how the body makes blood clotting factor IX. This gene is located on the X chromosome.

It is possible for the faulty gene to remain hidden over several generations because carriers of the gene can remain symptom free. If you or a member of your family are at all concerned about the possibility of inheriting or passing on haemophilia B, speak to your healthcare professional, who may refer you to a genetic counsellor or a specialist haemophilia centre.

QUICK FACT

The gene responsible for producing factor IX is on the X chromosome.• For this reason, it is unusual for haemophilia to affect females

because they carry two copies of the X chromosome

• Females are usually referred to as carriers

• Males have one X chromosome and one Y chromosome, hence there is no back-up X chromosome available

Haemophilia B 7

All daughters of a father with haemophilia will inherit his altered copy of the X chromosome.

None of the sons will be affected because they inherit their only X chromosome from their mother.

Carriers have one normal and one altered gene.

There is a 50% chance of passing the altered gene on to each child. Boys who inherit the altered gene from their mother will have haemophilia and girls will become carriers.

Father with haemophilia Carrier motherNon-carrier mother Non-affected father

Affected Not affectedNot affected Not affected CarrierCarrierCarrier

X X XY

X Y X Y XX Y X X XY X

X YX

X X

X

X X

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WHAT TO LOOK OUT FOR AS A HAEMOPHILIA B CARRIER

Female carriers often do not show symptoms of haemophilia. Although one X chromosome is abnormal, the other X chromosome generally works as normal to produce clotting factors.Around two-thirds of carriers will have no obvious bleeding problems. However, approximately one-third of carriers have clotting factor levels of less than 60% of normal and may experience abnormal bleeding. These symptomatic carriers can develop bleeding problems at different stages such as menstruation (menorrhagia), pregnancy or childbirth. They may also bruise more easily, bleed for longer or more severely after trauma, or require clotting factor support for delivery of their babies and during surgery.

Being a carrier of haemophilia can have a significant impact on a person’s physical and emotional health, well-being and quality of life. Therefore, carriers are encouraged to register with a haemophilia treatment centre, where professional counsellors are available to answer any questions or concerns.

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QUICK FACT

Although the symptoms of haemophilia B mostly affect males, some female carriers may experience symptoms of mild haemophilia.

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THE DIFFERENT TYPES OF HAEMOPHILIA B

The consequences of having haemophilia B (the frequency and severity of bleeding) depend on the severity of the disease, which is determined by clotting factor IX activity. The lower the clotting factor, the more frequent the bleeding in most cases.

Haemophilia B is classified according to three levels of severity: mild, moderate, or severe.A definitive diagnosis depends on factor assay to demonstrate deficiency of factor IX.

In the UK:

30% of patients have severe haemophilia B

30% of patients have moderate haemophilia B

40% of patients have mild haemophilia B

QUICK FACT

10 Haemophilia B

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SEVERELess than 1% of normal clotting factor activity

• Bleed often into the muscles or joints (mainly knees, elbows and ankles)

• Might bleed 1 or 2 times per week

• Might bleed for no clear reasonMODERATE1–5% of normal clotting factor activity

• Might bleed for a long time after surgery, a bad injury, or dental work

• Might bleed about once a month

• Rarely bleed for no clear reason

MILD5–30% of normal clotting factor activity

• Might bleed for a long time after surgery or a very bad injury

• Might never have a bleeding problem

• Do not bleed often

• Do not bleed unless injured

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HOW THE SEVERITY OF HAEMOPHILIA B MIGHT AFFECT YOU

12 Haemophilia B

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A diagnosis of haemophilia B is made after considering an individual’s medical history and the results of blood tests and genetic analyses. Haemophilia is usually suspected if an individual presents with a history of:

• Easy bruising in early childhood

• Spontaneous bleeding into joints, muscles and soft tissues

• Excessive bleeding after trauma or surgery

Symptoms of moderate or severe haemophilia B typically appear in infancy or childhood – usually around the time of crawling and learning to walk. The symptoms of milder forms of haemophilia usually appear a little later in life.

Classification of haemophilia

Most common types of bleeding

Usual causes of bleeding Frequency of bleeding (in the absence of prophylaxis)

MILD Bleeding at the lining of the nose and mouth

Internal bleeding

Serious sports injuries

Serious trauma

Dental extractions

Surgery

Quite rare

MODERATE All of the above, plus:

Joints

Muscles

Tissues

All of the above, plus:

Minor sports injuries

Spontaneous (no obvious cause, especially for those with factor levels of less than 2%)

Variable, depending on individual differences and factor levels

SEVERE All types All of the above, plus:

Spontaneous bleeds

Minor twists or bumps

Several episodes per month

A patient with severe haemophilia usually experiences spontaneous bleeding episodes generally involving major joints, muscles and soft tissues.Those with moderate haemophilia tend to bleed less often and bleeds are frequently the result of minor trauma, such as a sports injury.QUICK

FACT

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WHAT TO LOOK OUT FOR IF YOU HAVE HAEMOPHILIA B

HAEMORRHAGE INTO A JOINTAt first, the bleeding causes tightness in the joint with no real pain or any visible signs of bleeding. The joint then becomes swollen, hot to touch, and painful to bend. Eventually, movement in the joint will be temporarily lost.

BLEEDING OCCURS MOST OFTEN IN THESE AREAS

Elbow joint

Psoas muscle

Knee joint

Calf muscle

Ankle joint

Thigh muscle

Forearm muscle

Upper arm muscle

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Repeated bleeding in the same target joint can cause severe pain, stiffness and weakness, leading to haemophilic arthropathy. Sometimes bleeding can affect the muscles. If a bleed occurs in the deeper muscles, the swelling may press on nerves or arteries which will cause tingling and numbness.

An area of particular concern is the muscle that runs inside the pelvis along the inner side of the hip bone. These muscles (iliopsoas muscles) control movement of the upper thigh. Bleeds here are relatively common and recovery can be slow.

Joint bleeding is a primary concern for haemophilia B patients, with bleeding in the knees, elbows and ankles being the most common areas to look out for. Bleeding is often caused by minor injury – a bump or a slight twist of a joint. However, bleeding can also occur without obvious injury, especially in joints that have bled often in the past. The more a joint has bled, the easier it bleeds again with no external cause.

If you are experiencing a bleed, please contact your doctor who looks after your haemophilia.

QUICK FACT

Bleeding can occur on the body’s surface (external bleeding) or inside the body (internal bleeding).The main symptoms of haemophilia B are:

• Internal bleeding into or around the joints or other tissues

• Bleeding for prolonged periods after cuts or minor surgery

• Easy bruising

Joint damage is a result of repeated bleeding in and around the joint cavity.

• Permanent damage can be caused by one serious joint bleed or many bleeds into the same joint over a period of years

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WHAT OTHER PRECAUTIONS YOU SHOULD BE AWARE OF

SCHOOL AND EXTRACURRICULAR ACTIVITIESIt is important to dispel myths and provide accurate information to teachers and caretakers. They often need reassurance that people with haemophilia (1) do not bleed to death from cuts or scratches, (2) rarely experience external bleeding, and usually only after trauma and (3) typically bleed into joints and muscles.

They should be aware of the patient’s use of medication and which over-the-counter medications to avoid. If you are unclear about this please check with your haemophilia centre.

When patients participate in extracurricular activities, decisions will need to be made about transporting clotting factor replacement and supplies in the event of emergency. Some parents may choose to give prophylaxis on the day of the event, transporting their children to school and volunteering as chaperones on class trips.

DENTAL CARE AND MANAGEMENTGood oral hygiene is essential to prevent periodontal disease and dental caries, which predispose to gum bleeding.

Treating patients with haemophilia can be safely carried out under local anaesthesia using the full range of techniques available to dental surgeons. Dental extraction or surgical procedures carried out within the oral cavity should only be performed with a plan for haemostasis management and after consulting with the patient’s care team.

SURGERYSurgery for patients with haemophilia will require more planning and interaction with the healthcare team than is required for other patients. Surgery is best managed at or in consultation with a comprehensive haemophilia treatment centre.

EXERCISEExercise and physical activity are important for everybody, including people living with haemophilia. Talk to your doctor or haemophilia nurse about the best form of exercise for you. For most people with haemophilia, good forms of exercise include walking, swimming and cycling.

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QUICK FACT

Factor replacement treatment may be given before surgery, including dental work.Drugs that affect clotting, particularly acetylsalicylic acid (ASA) and non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, should be avoided. Paracetamol is an alternative.

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HOW HAEMOPHILIA B IS TREATED

Prophylaxis should be the goal of therapy to preserve normal joint and muscle function. In patients with severe haemophilia B, it is preferred over on-demand treatment because with regular injections spontaneous bleeds can be prevented in many individuals, which reduces the risk of long-term joint damage. Other treatments, such as pain relief and physiotherapy, may be recommended depending on the severity of the condition and on the individual’s needs.Most people with haemophilia B will be registered with, and treated by, a specialist haemophilia treatment centre.

• All people with haemophilia have the right of access to a Comprehensive Care Centre, which has the resources to cope with more complex treatment issues.

• Please visit the United Kingdom Haemophilia Centre Doctor’s Organisation website at http://www.ukhcdo.org/haemophiliacentresa-c/ to find the care centre closest to you

18 Haemophilia B

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YOUR HAEMOPHILIA TREATMENTIt is really important to work with your doctor to ensure you effectively manage your haemophilia.

The dose of treatment to be administered must be worked out carefully for each individual before it is started. Dosing will depend on: • Weight and age• Severity of the disorder• Severity of bleeding episode• Type of bleeding episode• Activity level• Venous access• Availability of clotting factor concentrates

QUICK FACT

Treating and preventing acute bleeds is the hallmark of effective haemophilia care.• Treatment for symptomatic haemophilia B is clotting factor

IX replacement therapy

• Clotting factor concentrates are given by injection into a vein – usually in the back of the hand or at the crook of the elbow

• The earlier the treatment is started after a bleed, the better it will be at controlling bleeds and further damage

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HOW YOU WILL ADMINISTER FACTOR REPLACEMENT THERAPYYou will be taught how to prepare and administer clotting factor by your haemophilia treatment centre so you can stop any bleeding quickly and effectively. Parents or carers can also be taught how to give clotting factor treatment at home, and experience has shown that young children can receive most of their treatment in the comfort of their own home.

QUICK FACT

Treatment from home means you have immediate access to your clotting factor treatmentImmediate access to clotting factor means:

• Decreased pain, dysfunction, and long-term disability• Fewer visits to the hospital • More freedom to travel• Greater employment stability

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PERFORMING VENIPUNCTUREA blood return lets you know the needle is in the vein in the right way. You must always check your blood return before injecting factor IX.

CENTRAL VENOUS ACCESS DEVICEA device that’s implanted under the skin, usually in the neck.

This is a type of catheter with a port, which is then threaded into a vein. This way, factor concentrates can be injected easily, without having to ‘find a vein’ for each injection.

ARTERIOVENOUS (AV) FISTULAAlthough peripheral veins are the preferred route for venous access, this is not always possible.

An AV fistula is created surgically by connecting an artery directly to a vein to direct more blood to flow into the vein. As a result, the vein grows larger and stronger, making repeated needle insertions easier.

Please see the patient leaflet inside the product pack for detailed information on storage and handling of your factor replacement therapy.

Port

Huber Needle

Tubing

Syringe

CatheterArtery

Skin

Vein, expanded due to increased blood pressure

Arteriovenous fistula

Mixed AV blood

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WHEN SHOULD YOU SEEK MEDICAL ASSISTANCE

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People with haemophilia are usually advised to seek medical help if:• There is injury to the neck, mouth,

tongue, face or eyes

• The head has received a severe knock and a headache develops

• There is heavy or persistent bleeding from any wound or blood in the vomit

• There is severe pain or swelling anywhere

• An open wound needs stitching

• There is a suspected fracture at any site

Most other bleeds (e.g. joint and muscle bleeds, small injuries and cuts not needing stitches, and nosebleeds) can be treated effectively at home, but individuals should always seek the advice of their haemophilia centre or healthcare professional if they have any concerns.

Although treatment for haemophilia B using clotting factor replacement therapy is effective, one of the most troublesome problems associated with it is that some people develop what are known as inhibitors, which can inactivate the replacement clotting factors.

Those who develop inhibitors may not respond adequately to factor replacement therapy or may develop an increased bleeding tendency. During this time they might need to receive more intensive clotting factor therapy or have alternative treatments for a while, to allow the blood levels of the inhibitors to settle down. In rare cases, haemophilia B inhibitors are associated with allergic reactions. When this happens, urgent specialist treatment is usually required.

Inhibitor development in haemophilia B is a documented side effect.Only <5% of people with haemophilia B develop inhibitors.

A special international medical card is available from the World Federation of Haemophilia. This is designed to provide information to others in the case of an emergency.

Reporting of side effects:

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed on the package leaflet of your medication. You can also report side effects directly via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard. By reporting side effects you can help provide more information on the safety of the medicine.

QUICK FACT

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GLOSSARY

CARRIERA carrier would have one normal and one altered copy of the gene. The clotting factors from their one normal X chromosome can help to prevent serious bleeding problems.

However, some carriers may still experience risk of bleeding.

CLOTTING FACTORA protein in blood that controls bleeding. There are several clotting factors circulating in the blood, with each playing a vital role in the clotting process. Haemophilia B patients are deficient in factor 9 – usually written in roman numerals as factor IX.

HAEMOPHILIC ARTHROPATHYPermanent joint disease occurring in haemophilia sufferers as a long-term consequence of repeated joint bleeds.

INHIBITORSInhibitors develop when the body’s own immune system sees the factor concentrate as a foreign agent and destroys it.

MENORRHAGIAHeavy bleeding during a menstrual period and/or prolonged menstrual bleeding (more than seven days). It is a gynaecological symptom potentially experienced by carriers of haemophilia. It can result in iron deficiency, anaemia and decreased quality of life in affected women.

ON-DEMANDTreatment given at the time of clinically evident bleeding.

PLASMAThe clear fluid part of the blood, making up about 55% of its overall content. Clotting factors are found in the plasma.

PROPHYLAXISTreatment by intravenous injection of factor concentrate in order to prevent anticipated bleeding. The goal is to keep the levels of factor IX in the blood high enough that bleeding does not happen.

SPORADIC HAEMOPHILIAHaemophilia may arise without previous family history. This type of haemophilia is caused by new mutations in a person’s genes.

SYMPTOMATIC CARRIERA female who has lower than normal clotting factor levels and has symptoms of factor deficiency.

TARGET JOINTOver time, if bleeding happens often at the same joint, the joint weakens and becomes prone to further bleeds. It is then known as a ‘target joint’.

X CHROMOSOMEThis is also known as the “sex chromosome” because it plays a role in determining whether a person is male or female. Females have XX chromosomes; males have XY chromosomes.

You may find the following organisations helpful if you would like to learn more about haemophilia B and its treatment.THE HAEMOPHILIA SOCIETYThe Haemophilia Society is the only UK-wide charity for everyone affected by a bleeding disorder; a community of individuals and families, healthcare professionals and supporters.

For more than 60 years, The Haemophilia Society has campaigned for better treatment and been a source of practical information and support. Their goal is to enable people living with long-term conditions to lead fulfilling lives, make informed choices about their treatment, care and support, and inspire others to do the same. To find out more, or to become a member for free, visit their website at haemophilia.org.uk or call them on 020 7939 0780. info@haemophilia.org.uk

FURTHER INFORMATION

HAEMOPHILIA SCOTLANDHaemophilia Scotland is a Scottish charity for people affected by bleeding disorders in Scotland. They provide independent information, direct support, and opportunities for affected people to support each other. By working closely with the Scottish Haemophilia Centres, NHS Scotland, and the Scottish Government they represent the interests of people with bleeding disorders. You can join for free or find out more at www.haemophilia.scot or by calling 0131 524 7186. hello@haemophilia.scot

HAEMOPHILIA WALESHaemophilia Wales provides information, support and advocacy to everyone with haemophilia, Von Willebrand disease and other bleeding disorders, including their families and carers. They work with Haemophilia Centres in Wales, the Welsh Commissioners through the All Wales Advisory Group on

Inherited Bleeding Disorders and have representation on the Cross Party Group on Haemophilia at the Welsh Assembly. You can find out more at www.haemophiliawales.org or contact them at info@haemophiliawales.org.

OTHER USEFUL WEBSITESwww.wfh.org The website for the World Federation of Haemophilia offers a broad range of information and publications, and has a handy database of all haemophilia treatment centres around the world.

www.ukhcdo.org The website for the UK Haemophilia Centre Doctors’ Organisation lists all UK haemophilia treatment centres.

www.medicalert.org.uk A registered charity offering a range of medic alert jewellery.

TEAR AND SHARE YOUR WALLET-SIZED CARD

Aside from these websites, your haemophilia nurse and other members of your care team will be able to answer any questions specific to the severity of your condition and lifestyle needs.

Please do not hesitate to reach out to them. You may also wish to pass along a wallet-sized card with their contact information to other carers, such as teachers, dentists or babysitters.

NAME

HAEMOPHILIA TREATMENT CENTRE

CONTACT INFORMATION

NAME

HAEMOPHILIA TREATMENT CENTRE

CONTACT INFORMATION

SHARE ME SHARE ME

Canadian Hemophilia Society. Chapter 7: Mild to moderate hemophilia. http://www.hemophilia.ca/files/GFFchap7.pdf Accessed on 26 April 2016.

Canadian Hemophilia Society. The History of Hemophilia. http://www.hemophilia.ca/en/bleeding-disorders/hemophilia-a-and-b/the-history-ofhemophilia/. Accessed on 26 April 2016.

Canadian Hemophilia Society. The symptoms of haemophilia. http://www.hemophilia.ca/en/bleeding-disorders/hemophilia-a-and-b/the-symptoms-of-hemophilia/. Accessed on 26 April 2016.

Colvin BT et al. European principles of haemophilia care. Haemophilia. 2008;14:361–74.

European Medicines Agency. EPAR summary for the public. BeneFIX. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Summary_for_the_public/human/000139/WC500020384.pdf. Accessed on 26 April 2016.

Giangrande PL. Six characters in search of an author: the history of the nomenclature of coagulation factors. Br J Haematol. 2003;121(5):703-12.

Knobek and Berntorpe. New treatments in haemophilia: insights for the clinician. Ther Adv Hematol. 2012;3(3):165-175.

National Hemophilia Foundation. The student with a bleeding disorder. http://www.hemophilia.org/sites/default/files/document/files/Nurses-Guide-Chapter-14-Student-with-a-Bleeding-Disorder.pdf. Accessed on 26 April 2016.

NHS Choices. Haemophilia- Causes. http://www.nhs.uk/Pages/Preview.aspx?site=Haemophilia&print=635392911362562479&JScript=1. Accessed on 26 April 2016.

NHS Choices. Haemophilia – Introduction. http://www.nhs.uk/Conditions/Haemophilia/Pages/Introduction.aspx. Accessed on 26 April 2016.

Parent Empowerment. Another Option for Venous Access in Children with Hemophilia: The Arterio-Venous Fistula. http://www.kelleycom.com/pen/may2003pen.pdf. Accessed on 26 April 2016.

Pfizerlife. Living with Haemophilia. https://www.pfizerlife.co.uk/health-matters/haemophilia/ more-than-medication. Accessed on 26 April 2016.

BIBLIOGRAPHY:

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United Kingdom Haemophilia Centres Doctors’ Organisation. UKHCDO Annual report 2017 including bleeding disorder statistics for 2016/2017. December 2017.

World Federation of Hemophilia. Guidelines for the Management of Hemophilia. http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2516.2012.02909.x/epdf. Accessed on 26 April 2016.

World Federation of Hemophilia. Looking after the veins. http://www1.wfh.org/publication/files/pdf-1174.pdf. Accessed on 26 April 2016.

World Federation of Hemophilia. Rehabilitation of Muscle Dysfunction in Hemophilia. http://www1.wfh.org/publication/files/pdf-1158.pdf. Accessed on 26 April 2016.

World Haemophilia Federation. What is Haemophilia? http://www1.wfh.org/publications/files/pdf-1324.pdf. Accessed on 26 April 2016.

World Health Organization. Genes and Human Diseases. http://www.who.int/genomics/public/geneticdiseases/en/index2.html#. Accessed on 26 April 2016.

This booklet has been organised and funded by Pfizer. Special thanks to Barbara Subel, Clinical Nurse Specialist, Katharine Dormandy Haemophilia Comprehensive Care Centre at the Royal Free Hampstead NHS Trust, and Jemma Efford, Clinical Nurse Specialist, Great Ormond Street Hospital Haemophilia Comprehensive Care Centre for their input and review.

CHANGING THE WORLD FOR PEOPLE WITH

HAEMOPHILIA

Date of Preparation: November 2018PP-GIP-GBR-3965