39 Haemoglobinopathy + obstetric haematology

Question 1

What is the role of globin in haemoglobin? (3).

Answer 1

Protects haem from oxidation.
Renders molecule soluble.
Permits variation in oxygen affinity.

Question 2

What type of heramoglobin does a foetus have?

Structure?

Answer 2

Hb-F.

2α/2γ

Question 3

What types of haemoglobin are physiological in an adult? Structures?

Answer 3

Hb-A 2α/2β 95%

Hb-A2 2α/2δ

Question 4

Simply explain the pathological basis of thalassaemias.

Answer 4

Change in globin gene expression leads to altered ratio of normal globin chains. Imbalance of production results in free chains which damage RBC membrane.

Question 5

What types of maternal testing are available for haemoglobinopathies?

Answer 5

Genetic.

Antenatal screening.

Question 6

When does physiological anaemia and macrocytosis occur?
When is this maximal?
Why does the MCV increase?

Answer 6

Pregnancy.
Plasma increases 50%, RBC increases 25%.
Haemodilution maximal at 32 weeks.
MCV increase due to Fe mobilisation.

Question 7

Describe the leukocytosis seen physiologically in pregnancy:

Answer 7

Mainly neutrophilic - peak 9-12 in 3rd trimester.

Also left shift: myelocytes + metamomyelocytes.

Question 8

When does gestational thrombocytopenia occur?

Answer 8

Week 20, most marked in late pregnancy.

Question 9

What are the pregnancy associated causes of thrombocytopenia in pregnancy? (6).

Answer 9

Severe folate deficiency.
Gestational.
Pre-eclampisa/HELLP.
AFLP (acute fatty liver of pregnancy).
DIC.
TTP/HUS.

Question 10

What are the causes of the prothrombotic state seen in pregnancy? (4).

Answer 10

Platelet activation.
Increase in coagulation factors (esp fibrinogen, V, VII, VIIII, X, XII).
Decrease in fibrinolysis.
Reduction in natural anticoagulants.

Question 11

What is Kleihauer testing and Supravital staining used for?

Answer 11

Diagnosis of haemoglobinopathies.

Question 12

What is the protein change in sickle cell anaemia?

Answer 12

Valine substituted for glutamine at position 6 of β-globin gene.
Hb-S polymerises at low oxygen levels, distorting RBC into sickle shape.

Question 13

Why is sickle cell anaemia not symptomatic for the first six months of life?

Answer 13

Presence of Hb-F reduced polymerisation levels.

Question 14

What is the inflammatory basis of sickle cell anaemia?

Answer 14

Haemolytic anaemia releases haemoglobin into plasma.
Haemoglobin decreases NO conc and generates free radicals.
Arginase I is also released, preventing NO production.
Low NO levels lead to platelet activation and tissue factor expression.

Question 15

What is sickle cell trait?

Clinical picture?

Answer 15

Hb-S 45%, Hb-A 55%

No problems except in extreme hypoxia or dehydration.

Question 16

What are the results of blood count and Hb electrophoresis in sickle cell disease?

Answer 16

Anaemia.
> 95% Hb-S.
OR βs and another β chain abnormality.

Question 17

What are the acute complications of sickle cell disease? (4).

Answer 17

Acute vaso-occlusive crisis: priapism, chest syndrome, dactylitis.
Septicaemia.
Aplastic crisis.
Acute sequestration crisis (liver+spleen).

Question 18

What are the chronic complications of sickle cell disease? (7).

Answer 18

Hyposplenism (infarction).
Renal disease.
Avascular necrosis: femoral/humeral heads.
Leg ulcers
Osteomyelitis
Gall stones
Retinopathy.

Question 19

What is the treatment for sickle cell disease? (6).

Answer 19

Penicillin
Analgesia
Hydration.
Transfusion top up/exchange (regular for stroke prevention).
Hydroxycarbamide (increases Hb-F).
Bone marrow transplant.

Question 20

What is Hb Barts?

Answer 20

Homozygous inheritance of A0. Causes still birth.

Question 21

Differentiate between thalassaemia minor and major.

Answer 21

Minor: carrier, clinically normal.
Major: homozygotes, in β usually fatal.

Question 22

What is thalassaemia pathology due to?

Answer 22

α : too many β chains.

β : too many α chains.

Question 23

What is the blood picture in β-thalassaemia minor? (3)

Answer 23

Small, pale red cells.
Slight reduction in Hb.
Increased Hb-A2 levels.

Question 24

What are the complications of β-thalassaemia intermedia? (5).

Answer 24

Pulmonary hypertension.
Extra medullary haematopoesis.
Osteoporosis.
DM and hypothyroidism.
Leg ulcers.

Question 25

What is the pathological basis of β-thalassaemia major?
Effect on bone marrow:
Effect on spleen:

Answer 25

Alpha chain excess.
Reduced RBC production + shortened lifespan.
Increased bone marrow activity: skeletal abnormality, increased iron absorption, protein malnutrition.
Enlarged spleen: RBC pooling, increased transfusion requirement.

Question 26

Describe thalassaemic facies: (3).

Answer 26

Maxillary hypertrophy.
Abnormal dentition.
Frontal bossing due to expanded marrow.

Question 27

How is β-thalassaemia major treated?

Answer 27

4x weekly blood transfusion to maintain Hb and suppress marrow production/spleen enlargement.

Question 28

What does iron overload cause? (4)

Answer 28

Growth and puberty failure.
Dilated cardiomyopathy.
Diabetes.
Liver cirrhosis.

Question 29

How is death from iron overload prevented in β-thalassaemia major? (3)

Answer 29

Iron chelation: Desferrioxamine (IV), Deferiprone (Oral) and Deferasirox (Oral).

Question 30

What is the cure rate of bone marrow translation in β-thalassaemia major?
When does it have to occur?

Answer 30

60-80%.

Before one year of life and iron overload.