1. J Hall Haemoglobinopathy Counsellor
Haemoglobinopathies
J Hall
Haemoglobinopathy Counsellor

2. There are approximately 1200 different types of Haemoglobin
Normal Haemoglobin:
consists of
Four Globin chains each holding a molecule that contains iron
Globin A complex protein containing a precise number of amino acids

3. Adult Haemoglobin (Hb AA) = 4 Globin Chains 2 Alpha
2 Beta Globin Chains
Fetus and New Born Infant
Mainly fetal haemoglobin (Hb F)
2 Gamma Globin Chains

4. Production of the three types of Globin Chains
Controlled by three different pairs of genes
Alpha Genes are active in fetal and adult life
Gamma Genes active in fetal life then replaced by Beta Genes about the time of birth

5. Abnormalities or Variations within the Globin Chains
In Thalassaemia leads to an
Absence of production or
Diminished production of Haemoglobin

6. Thalassaemia Reduced production of Beta Globin chains
The blood cells are small Microcytic
Do not contain as much iron Hypochromic

7. Haemoglobinopathies
Thalassaemia is an inherited blood disorder affecting the production of normal adult Haemoglobin. It mainly, but not exclusively affects people from black and minority ethnic groups.
The frequency of many Haemoglobinopathies including Thalassaemia relates to the geographic distribution of MALARIA.
Estimated that over 6% of the population of England and 11% of births are in groups at risk of Haemoglobin disorders.

8. Thalassaemia Trait
Carrier state for the Disorder often confused with Iron deficiency due to reduced MCV and MCH
Check serum Ferritin
Normal Hb A
Hb A2 above 3.3-Diagnostic

9. Most Common Haemoglobinopathy Traits
Beta Thalassaemia Trait
Haemoglobin E Trait
Haemoglobin D
Haemoglobin C
Haemoglobin S
Alpha-Zero Thalassaemia Trait
Alpha-Plus Thalassaemia Trait

10. Mode of Inheritence
Known as Autosomal Recessive disorders

11. When one parent carries the trait
In each Pregnancy
There is a 1 in 2 chance that the child will be a carrier
There is a 1 in 2 chance that the child will be normal

12. Where both parents are carriers of the disorder
In each Pregnancy
There is a 1 in 4 chance the child will have the disorder
There is a 1 in 4 chance that the child will be normal
There is a 1 in 2 chance that the child will be a carrier of the trait

13. Major Haemoglobin Disorders
Beta Thalassaemia Major
Haemoglobin E/Beta Thalassaemia
Alpha Zero Thalassaemia
(Hydrops Fatalis)
Haemoglobin H Disease
Sickle Cell disorders

14. Major Haemoglobin Disorders
The major Haemoglobin disorders are life long illnesses. Most are forms of anaemia and some more severe than others, they fall in to two groups:
Thalassaemias
Sickle Cell Disorders

15. Thalassaemia Most common single gene disorder
First recognised in 1925 by Thomas Cooley
Also known as Cooley’s Anaemia
Later it was noticed that many patients with the disorder came from the mediterranean region hence the Greek word “Thalassa” meaning from the sea.

16. Prevalence
Mainly found in people with origins from Pakistan, India, Bangladesh, Sri-Lanka and countries from around the mediterranean.
In the UK 78% of babies with the disorder are Asian

17. Beta Thalassaemia Most Common type of Thalassaemia
A disorder of the Beta Globin genes, affecting adult Haemoglobin.
Beta Thalassaemia trait in the carrier form has no affect upon the individuals general health

18. Beta Thalassaemia Major
Symptoms arise from about 3-6 months of age
Children with Thalassaemia Major are healthy at birth due to the presence of fetal haemoglobin
They become severely anaemic
(Typical Haemoglobin level below 7gm/dl)
before they reach 2 years of age

19. Untreated children with Thalassaemia Major
are
severely anaemic
failure to thrive
Irritable
Stunted growth
Enlarged liver and spleen

21. 17 year old girl with Beta Thalassaemia Major
Showing reduced stature Height 134cms and delayed pubertal development.
Since circulating growth hormone levels are usually normal, the lack of growth is due to endocrine organ failure.

22. Skeletal Changes
The Bone Marrow expands greatly as it tries (uselessly) to make red cells. This weakens and distends the bones, particularly the bones of the face and skull.
This is why the children with Thalassaemia Major develop a characteristic facial appearance.

25. Splenic Changes
During the course of the disease the spleen, which normally destroys the old red blood cells begins to destroy young red blood cells worsening the anaemia.

27. Mortality
Most untreated children die from anaemia or infections before 2 and at most 5 years of age.
Treatment
The current treatment for Thalassaemia Major is blood transfusions every 4 weeks for life.
This results in good health mainly in the short term.

28. Side effects of this treatment
Blood contains a great deal of iron which gradually accumulates in the body.
Iron can damage the liver, heart and other major organs. Unless it is removed it can cause premature death through organ failure. The most common being Heart failure, this occurs between years of age.

29. Drug Treatment
Iron can be removed by a drug called Desferrioxamine, it is infused subcutaneously through a fine needle attached to a small pump or syringe driver.
Its action is to bind with the iron and then be excreted in the urine.
This procedure takes 8-12 hours and has to be carried out 5-6 times a week.

30. Compliance
Having the treatment regularly patients with Thalassaemia Major can live up to 50 years plus leading a reasonably normal life.
However this form of treatment is very hard to comply with and as no ill effects are experienced until organ damage is sustained the main factor contributing to premature death particularly in young people is
Organ failure due to Non-compliance.

31. Innovations in current Drug Therapy
Oral chelator’s _ L1 Deferiprone and the latest Exjade Deferasirox.
(L1 has been on the market for 10 years initially on a named patient basis only but is now available and commonly used in combination therapy with Desferioxamine
Exjade has recently been developed and trialled, relatively free of side effects, the iron is
excreted predominately in the faeces.

32. Innovations in Current Treatment
Combination drug therapy specific to the individuals need.
T2* MRI and more recently the Ferriscan technique specific in identifying organs which are affected by iron overload
Baxter Pumps
Home delivery of equipment and preparations ready to use

33. Bone Marrow Transplant
This procedure is available to children preferably below 7 years of age who have a
Matching HLA (Human Leucocyte Antigen).
Genotypically matched sibling only
About 30% of patients will have a sibling match

34. Complications
Arise due to Graft V Host Disease, which may be acute or chronic.
A life threatening disorder affecting the skin, gastro-intestinal tract, liver and with rejection of the bone marrow.
The mortality and morbidity rate is between 93% and 91% transplant related mortality of 7%
At risk factor ( Liver disease) & poor chelation history, disease free survival 79% & 58% with 10% risk of death during proceedure

35. Alpha Plus Thalassaemia (Otherwise known as Alpha Thalassaemia Trait)
A carrier state of one or two gene deletion
This is a mild form of Alpha Thalassaemia
It can be difficult to identify as the haemoglobin is only minimally lowered and electrophoresis is normal
Definitive diagnosis requires DNA analysis
At present all our DNA tests are carried out at a specialist laboratory in Oxford.

36. Alpha Zero Thalassaemia Major
Otherwise known as Hydrops Fetalis or
Bart’s Hydrops Fatalis
This occurs when the fetus inherits
Alpha zero Thalassaemia from both parents
The fetus has no Alpha genes and can not make an alpha chains
This means that it cannot make any fetal haemoglobin.

37. Alpha Zero Thalassaemia
This is a fatal anaemia
The Fetus
Develops normally for the first 5 months of pregnancy, sometimes longer then growth slows, its heart begins to fail and its body and the placenta becomes swollen with fluid.

38. The Mother Can develop Pre-Eclampsia or even Eclampsia
The baby may be born at any time between the 28th and 42nd week of pregnancy
Complications at delivery
Include obstructed labour and excessive bleeding, if the baby has not died in the womb it will die shortly after birth.

39. Alpha Zero Thalassaemia Major.
There is no treatment
For couples at risk of having a baby with this disorder, there is a 1 in 4 chance of a still birth or neonatal death in every pregnancy

41. Beta Thalassaemia Major
PREGNANCY
Beta Thalassaemia Major
Early booking with joint management by the Obstetrician and Haemotologist
Correction and prevention of anaemia
Serial scans for fetal growth
Prompt treatment of infection

42. The Fetus The fetus is not directly affected in Utero
by Beta Thalassaemia as it is protected by fetal haemoglobin.
Symptoms start to arise when the infant
is unable to produce normal adult haemoglobin from six months of age

43. Ante- Natal Diagnosis If both partners are Carriers
Pregnancy identified as “At Risk”
Chorionic villus sampling carried out between weeks
Amniocentesis from 15 weeks
Fetal blood sampling some times carried out in late pregnancy for rapid DNA analysis

45. Chorionic Villus Sampling
Has the advantage of being carried out in the 1st trimester of pregnancy.
The timing falls within the limits set for a (Therapeutic Abortion) in many religons and reduces the emotional stresses of Pre-Natal diagnosis.

46. LABORATORY SCREENING All Antenatal women identified or known to have
Haemoglobinopathy should be treated as urgent The midwife informed by the paper copy stating the disorder or carrier status.
The counsellor by telephone in the first instance and followed with a paper copy .
Time is of an essence to allow for partner testing and PND if required.

47. Pre-Natal Diagnosis
It is well documented that the most important factors influencing a couples choice for or against PND
Severity of the disorder
Stage of pregnancy at counselling

48. Preferably before Pregnancy
Counselling
Preferably before Pregnancy
Sensitive to the Needs of the couple
Issues such as
Level of Risk
Pre -natal diagnosis and in the case of an affected child informed choice and support

49. Points to remember
If it is a subsequent pregnancy we cannot assume that the husband/partner is the same.
That they are aware of their carrier status or if they are, have communicated it to the midwife
That they have booked with the midwife early or in plenty of time for PND
Ideally the women should have been booked, counselled, partner tested and referred for Prenatal Diagnosis by week 11-13

50. Issues
Communication
Ethical
Economic
Stigmatisation
Culture