Haemoglobinopathies are genetically inherited blood disorders caused by abnormalities in the haemoglobin protein. The most common types are sickle cell anaemia and thalassaemia. Sickle cell anaemia results from abnormal haemoglobin HbS which causes red blood cells to become sickle shaped and destroy easily. Thalassaemia involves absent or reduced globin chains leading to anaemia. Management involves treating crises, infections, and anemia with blood transfusions and medications. Pregnancy requires special care due to risks of complications.

1. Haemoglobinopathies

2. Haemoglobin
 Haemoglobin consists of:-
 Haem – an iron containing pigment
 4 rings each containing one iron
 One iron can attach to one O2 molecule
 Globin –a protein containing 4 chains of
amino acids surrounding haem

3. Haemoglobin molecule

4. Normal Haemoglobin
 4 types of globin
 Alpha (α) , Beta (β), Delta (δ), Gamma (γ)
 Adult Haemoglobin consists of:-
 HbA 2 α and 2 β97%
 HbA2 2 α and 2 δ > 3%
 HbF 2 α and 2 γ >1.5%

5. Haemoglobinopathies
 Genetically inherited conditions.
 Adult HbA partially or wholly replaced
by one or more abnormal type e.g. HbS
Commonest types are:-
 Sickle cell anaemia
 Thalassaemia

6. Haemoglobinopathies
Causes
Impaired synthesis of Hb and thus red cell
production
→ Anaemia
→ Reduced survival time of RBC’s in the
circulation

7. Sickle cell anaemia
 Common in Afro-Caribbean races
 HbA is replaced by abnormal β chain
 RBC life span of 10 –30 days (normal 120)
 Protection against malaria
 Abnormal RBC becomes crescent or sickle
shaped when O2 released
 Regains shape when oxygen reattaches
 Repeated changes in shape damages Hb
and RBC

8. Hb inheritance pattern
 HbAA is normal (Homozygous)
 HbAS Sickle cell carrier – sickle cell trait
(heterozygous)
 HbSS sickle cell anaemia
(Homozygous)
 Where both parents are carriers of the
abnormal gene there is a 1:4 chance of
offspring having sickle cell disease

9. Pattern of Hb inheritance
Father
HbA HbS
Mother
HbA HbAA HbAS
HbS HbAS HBSS

10. Sickled cells
Inflexible
 Cannot pass through capillary vessels
 Clump together
 Obstruct the blood flow
Result in
 Tissue hypoxia
 Tissue damage
 RBC damage – haemolysis
 Anaemia

11. Clinical features
Present from birth, symptoms rare before
3 -6 months
Main symptoms (a result of vascular occlusion)
 Episodes of pain in joints
 Anaemia
 Erythropoieisis cannot keep pace with the
haemolysis
 Infection – minor and life threatening
 Septicaemia, pneumococcal meningitis and
osteomyelitis

12. Management
 Analgesia
 IV fluids
 Oxygen therapy
 Antibiotic therapy
 Observation of vital signs
 Emotional support

13. Acute splenic sequestration
 Sickle cells trapped in the spleen
 Rapid drop in Hb
 Enlargement of spleen
 Rapid onset of
 Abdominal pain
 Shock
 Dyspnoea
 Tachycardia

14. Treatment of acute episode
 Admit ICU
 Blood transfusion
 Emergency splenectomy

15. Contributory factors to sickle
cell crisis
 Strenuous exercise
 Dehydration
 Emotional stress
 Air travel
 Sudden changes in temperature
 Pyrexia
 Infection
 Anaesthetics
 Pregnancy / labour

16. Effect on pregnancy
 Reduced fertility
 ↑ risk of abortion / stillbirth
 Anaemia
 Infection
 Pre-eclampsia
 Pre-term labour

17. Effect on fetus
 IUGR
 Low birth weight
 Pre-term birth

18. Management (prenatal)
1:400 women at risk in UK
 Screen those at risk
 Attention to ethnic, religious, cultural issues
 Folic acid
 Monitor for impending crisis and treat
 Support agencies
 Education re diet, fluid intake and avoidance
of infection

19. Management (labour)
 Specialist obstetric unit
 Avoid dehydration, infection, sickling
 Blood x matched
 Antibiotics
 Hb & PCV 6hrly
 Urinalysis (proteinuria may indicate
impending crisis)
 Epidural analgesia

20. Management (postnatal)
 Observe for signs of crisis
 Treat anaemia
 Education / support with baby care
 Contraception
 Screening & counselling for long term
care

21. Sickle cell trait
 Few symptoms
 May be increased incidence of UTI in
pregnancy (asymptomatic)
 Haematuria due to sickling in fine
capillaries of the kidney
 Increased fetal distress in labour

22. Thalassaemia
Associated with Mediterranean races & Central
Asia
 α chain or β chain missing
 abnormal amounts of HbA
2
 Severity depends on :
 Whether defective gene is inherited from one or
both parents
 Mode of genes inherited

23. Alpha Thalassaemia Major
 2 abnormal genes inherited from
parents, incompatible with life
 Results in stillborn baby – hydrops
fetalis

24. Alpha Thalassaemia Minor
One defective α gene inherited
Compatible with life
 1 defective gene –clinically undetected
carrier

25. Treatment
Major – a variant allows some to survive.
Severe anaemia – regular blood
transfusions
Minor : symptoms similar to iron
deficiency anaemia, Hb, MCV and MCH
are all lowered
Folic acid and folic acid supplements
prescribed NOT iron

26. Beta Thalassaemia (Major)
 2 defective β chains inherited
 Individual suffers from severe anaemia
 Not usually deficient in iron (iron stored
in liver following haemolysis)
 May develop cardiac failure in
childhood
 Frequent blood transfusions prolong
lifespan (30years)

27. Beta Thalassaemia (Minor)
 One abnormal gene β chain inherited
 75% Hb normal
 May develop symptoms of iron
deficiency anaemia
 Hb, MCV and MCH all lowered
 Folic acid and folic acid supplements
prescribed NOT iron

28. Investigations / diagnosis
 Screening women & partners in
vulnerable groups
 Counselling
 Complete haematological screening
 Electrophoresis
 Quantitative test

29. Management in pregnancy
 Genetic counselling
 CVS screening
 Treat anaemia with folic acid NOT iron
 Other care as for sickle cell anaemia
 Screen baby when born