39 Haemoglobinopathy + obstetric haematology Flashcards Preview

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Flashcards in 39 Haemoglobinopathy + obstetric haematology Deck (30)
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1
Q

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

A

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

2
Q

What type of heramoglobin does a foetus have?

Structure?

A

Hb-F.

2α/2γ

3
Q

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

A

Hb-A 2α/2β 95%

Hb-A2 2α/2δ

4
Q

Simply explain the pathological basis of thalassaemias.

A

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

5
Q

What types of maternal testing are available for haemoglobinopathies?

A

Genetic.

Antenatal screening.

6
Q

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

A

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

7
Q

Describe the leukocytosis seen physiologically in pregnancy:

A

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

Also left shift: myelocytes + metamomyelocytes.

8
Q

When does gestational thrombocytopenia occur?

A

Week 20, most marked in late pregnancy.

9
Q

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

A
Severe folate deficiency.
Gestational.
Pre-eclampisa/HELLP.
AFLP (acute fatty liver of pregnancy).
DIC.
TTP/HUS.
10
Q

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

A

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

11
Q

What is Kleihauer testing and Supravital staining used for?

A

Diagnosis of haemoglobinopathies.

12
Q

What is the protein change in sickle cell anaemia?

A

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

13
Q

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

A

Presence of Hb-F reduced polymerisation levels.

14
Q

What is the inflammatory basis of sickle cell anaemia?

A

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.

15
Q

What is sickle cell trait?

Clinical picture?

A

Hb-S 45%, Hb-A 55%

No problems except in extreme hypoxia or dehydration.

16
Q

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

A

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

17
Q

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

A

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

18
Q

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

A
Hyposplenism (infarction).
Renal disease.
Avascular necrosis: femoral/humeral heads.
Leg ulcers
Osteomyelitis
Gall stones
Retinopathy.
19
Q

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

A
Penicillin
Analgesia
Hydration.
Transfusion top up/exchange (regular for stroke prevention).
Hydroxycarbamide (increases Hb-F).
Bone marrow transplant.
20
Q

What is Hb Barts?

A

Homozygous inheritance of A0. Causes still birth.

21
Q

Differentiate between thalassaemia minor and major.

A

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

22
Q

What is thalassaemia pathology due to?

A

α : too many β chains.

β : too many α chains.

23
Q

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

A

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

24
Q

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

A
Pulmonary hypertension.
Extra medullary haematopoesis.
Osteoporosis.
DM and hypothyroidism.
Leg ulcers.
25
Q

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

A

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.

26
Q

Describe thalassaemic facies: (3).

A

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

27
Q

How is β-thalassaemia major treated?

A

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

28
Q

What does iron overload cause? (4)

A

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

29
Q

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

A

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

30
Q

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

A

60-80%.

Before one year of life and iron overload.

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