Approach to the involvedApproach to the involved populations. p p

Ongoing programs. Planned programs.

D Mi h l A ti i tiDr Michael AngastiniotisThalassaemia International Federation

2nd European Hemoglobinopathy Forum Madrid 29th November 2011

Why prevention?

Relevance to thalassaemia patients

Relevance to prospective parents: at-risk couplesrisk couples

Relevance to the community: public y phealth issues.

Relevance to patients

Optimum treatment is required for p qsurvival and quality of life

N t t t l d thNo treatment means early death.

Less treatment means poor quality ofLess treatment means poor quality of life and early death.

P ti tPatient care

Voluntary blood donation and adequate suppliesSafe bloodProvision of essential drugs chelatingProvision of essential drugs chelating agentsFree medical treatmentExpert reference centers. Quality of care.p yMultidisciplinary care

Increase in blood requirementsEstimates for Cyprusyp

If no prevention Blood requirements units/year

50000

200003000040000

Bloodrequirements

01000020000 requirements

units/year

01 4 7 10 13 16 19 22

Extent of Clinical Management and Prevention gAcross the World

BLOOD

AustraliaRussia

South Africa

BLOOD TRANSFUSION IRON CHELATION PREVENTION

ArgentinaBrazil

GreeceItaly

AlbaniaBulgaria

RomaniaPalestine

CyprusEgyptgyp

LebanonJordan

IraqIran

MaldivesMalaysiaThailand

Indonesia (1000)China

Hong Kong Prenatal IndonesiaSri Lanka

India

Diagnosis

Screening

Relevance to at-risk couples

The right to healthy childrenTh i ht t i f tiThe right to informationThe right not to knowThe right to choose

C l h tiCouples who carry a genetic disorderdisorder

Reproductive options:Remain childless

Reproductive options:

Take a chance, risk of having an affected childPrenatal diagnosis Pre implantation Genetic Diagnosis (PGD)Pre-implantation Genetic Diagnosis (PGD)Gamete donation (artificial insemination)Adoption

P ti t t iPrevention strategies

Public education and awarenessPopulation screening Specialised labsPopulation screening. Specialised labsGenetic counselling. Counsellors?Prenatal diagnosisPre-implantation diagnosisPre-implantation diagnosisEthical principles: voluntary, autonomy

f l i ht t f llof couples, right to full information, confidentiality: informed choicechoice

Developing a prevention serviceGeneral Strategies and Plans:General Strategies and Plans:1. Epidemiological knowledge

2. National support and control

3 Education of the public3. Education of the public

4. Manpower planning and qualifications

5. Laboratory infrastructure

6 Screening policies PND PGD6. Screening policies, PND, PGD

7. Legal and ethical considerations

Epidemiological knowledge:

• Need to know the frequencies and prevalence in each country

• Need for micromapping in order to best locate services

• Need to know the rate of consanguinity

Need to estimate the expected annual• Need to estimate the expected annual affected births

S i i di t• Service indicators

Micromapping - Indiapp g

INDIA (many religions and cultures)

● 50,000 – 60,000 , ,strictly indigenous communities

● Expected/anticipated annual births with

iserious Hbpathies:32,400

Countries with a national program for prevention

Middle - East• Tunisia

Asia• Thailand

• Lebanon• Jordan

• Maldives• Malaysia

• Iran• Bahrain

y• Taiwan• Singapore

• Saudi Arabia• UAE

g p• Hong Kong

UAE• Kuwait• QatarQatar

Countries where a national program for prevention is being negotiated by TIF

Expected affected births Country• Albania

pper year

35• Bulgaria• Romania

115

• Azerbaijan 2 03

Countries where a national program for prevention is being negotiated by TIF

Expected affected births Country• Algeria

pper year

123g• Morocco• Egypt

146400-1300gyp

• Syria• Palestine

32775

• Iraq• Pakistan

5022891Pakistan

• Yemen2891145

Countries where a national program for prevention is being negotiated by TIF

Expected affected births Country• China (5 provinces)

pper year

1879( p )• India• Bangladesh

152316435g

• Nepal• Sri-Lanka

84880

• Indonesia• Cambodia

96191753Cambodia

• Philippines175392

Screening

The timely identification of carriersThe timely identification of carriers at risk

B f iBefore screening

Do a survey or use existing data to know h t th l i d i twhat thalassaemia genes and variants

are found in your population and the ffrequency.Interactions of these genes may alter the g yhaematological expression/ lab findings – source of confusion and error.

Health education / pre-Health education / pre-screening counselling

Education of the public – they must be aware f h th b i d

g g

of why they are being screenedThey must be told what thalassaemia isWhat is the life of a homozygote likeWhat are the chances of being a carrierWhat are the chances of being a carrierThe consequences when two carriers marryThe right not to know is respected

European Council Convention on HumanEuropean Council Convention on HumanRights and Biomedicine

P l ti iPopulation screening

Decide policy:

When to screen?Who to screen?Who does the screening – which labs.?What laboratory techniques?

Whi h l b t i ?Which laboratories?

Reference laboratoryRed cell counter, HPLC, Cap electrophoresis, molecularp ,

P i h l H it lPeripheral Hospital lab: Indices, A2,

gel electrophoresis

Field lab OF, DCIP

Primary care labOF, DCIP, indicesg p

Th f l b tThe reference laboratoryMeasurement of haematological indices using automated counters.Red blood cell morphology.p gyHigh Performance Liquid chromatography (HPLC) for haemoglobin analysis or Capillary(HPLC) for haemoglobin analysis or Capillary Electrophoresis.Preparation of haemolysate from whole bloodPreparation of haemolysate from whole bloodElectrophoretic techniques.

a)a) Separation andSeparation and quantitationquantitation ofof haemoglobinshaemoglobins bybya)a) Separation and Separation and quantitationquantitation of of haemoglobinshaemoglobins by by cellulose acetate electrophoresis with elution buffecellulose acetate electrophoresis with elution buffeat pH 8.4at pH 8.4

b)b) A l l t h i t H 6 3A l l t h i t H 6 3b)b) Agar gel electrophoresis at pH=6.3Agar gel electrophoresis at pH=6.3

M l l t diMolecular studiesTo finalise the diagnosis DNA studies are carriedTo finalise the diagnosis DNA studies are carried out in the following cases:

1. Individuals suspected for α-thalassaemia2. Couples suspected for H-disease3. Couples suspected for hydrops-foetalis4. Cases suspected for H-disease/β-thalassaemia5. Cases with borderline HbA2 levels, low indices

and when family studies are not available6. When the biosynthetic ratio indicates the

presence of any α or β thalassaemia mutation

S i l ithScreening algorithm