Haemoglobinopathies and Obstetric Haematology

Question 1

Antenatal Haemoglobinopathy screening

Answer 1

• Family origin + FBC

- Partner testing

Question 2

Postnatal Haemoglobinopathy screening

Answer 2

• Newborn screening at 5 days

- Heel prick test - analysis of dried blood spot

Question 3

Physiological macrocytic anaemia - changes in pregnancy

Answer 3

• Plasma volume expands by 50%
• RBC mass increases
• Haemodilution occurs, maximally at 32 weeks

Question 4

Leucocytosis - changes in pregnancy

Answer 4

• Mainly neutrophilia
• Levels rise from second month
• Peak range of 9-15 in 2nd-3rd trimester
• Left shift = spilling out of cells that normally live in the bone marrow

Question 5

Gestational thrombocytopenia - changes in pregnancy

Answer 5

• Platelet count falls after 20 weeks and thrombocytopenia is most marked in late pregnancy
• Usually resolves after pregnancy

Question 6

Coagulation - changes in pregnancy

Answer 6

• pregnancy is a pro-thrombotic state
• Evidence of platelet activation
• Increase in plasma fibrinogen

Question 7

Haemoglobinopathies

Answer 7

• Changes in globin genes
• AR inheritance
• Single point mutations cause structural Hb variants - HbS (sickle)

Question 8

Sickle cell Disease cause

Answer 8

• Substitution of valine for glutamic acid in position 6 in the beta globin chain results in a HbS

Question 9

Heterozygous (HbA/HbS)

Answer 9

• HbS 45%, HbA 55%

- No problems except when extreme hypoxia/dehydration

Question 10

Homozygous (HbS/HbS)

Answer 10

• Blood count - chronic haemolytic anaemia (Hb 60-80)
• HbS >95%, HbA 0%
• Stuck in vessels - cause ischaemia to tissue = painful sickle crises
• More likely clots form

Question 11

Acute complications of Sickle cell

Answer 11

• Vaso-occlusive crisis – inflammation of hands/feet
• septicaemia
• sequestration crisis (obstruction of spleen/liver - jaundice)

Question 12

Chronic complications of Sickle cell

Answer 12

• Hyposplenism - more prone to sepsis
• Renal disease - tubular damage, chronic renal failure
• Avascular necrosis - femoral/humeral heads

Question 13

Treatment of sickle cell

Answer 13

• Penicillin from 6 months
• Vaso-occlusive – analgesia (opiates), hydration, treatment of precipitants
• Hydroxycarbamide – increases HbF
• Transfusion

Question 14

Thalassaemia

Answer 14

• Most common single gene disorders
• Problem lies in the rate of globin chains produced. In some, no globin chain is produced (e.g. a0 gene), on others they are produced at a reduced rate (e.g. a+ gene). Causes ineffective erythropoiesis = RBC breakdown/short life span = anaemia

Question 15

Alpha thalassaemia

Answer 15

• restricted to SE Asia and Mediterranean Islands
• both HbA and F affected
• Hb Barts - no alpha chains produced causing hydrops fetalis
• HbH disease = alpha thalassaemia where there is reduced alpha globin formed (3 genes deleted)

Question 16

Beta thalassaemia

Answer 16

• Reduced rate of production of beta-globin chains
• Blood picture resembles iron deficiency
• Total Hb level is normal or slightly reduced

Question 17

hydrops fetalis

Answer 17

abnormal accumulation of fluid in two/+ foetal compartments; survives few months and foetus dies invitro due to heart failure due to severe anaemia

Question 18

How many genes code for the alpha chain

Answer 18

4

Question 19

How many genes code for the beta chain

Answer 19

2

Question 20

Beta thalassaemia major

Answer 20

• Double deletion of beta genes, cant make normal Hb= death from heat failure/infection in first years
• blood film abnormal - lots of nucleated red cells
• Caused by shortened RBC lifespan, Increased marrow activity, Enlarged and overactive spleen

Question 21

Clinical features of Beta thalassaemia major

Answer 21

• Short stature and distorted
• Limb growth
• Enlarged liver and spleen due to extramedullary haematopoiesis
• Thalassemic facies = maxillary hypertrophy, abnormal dentition, frontal bossing due to expanded bone marrow
• X-ray showing classical “hair on end” skull due to widening of diploic cavities by marrow expansion

Question 22

Treatment of thalassaemia

Answer 22

• Transfusion to maintain Hb levels at 120g/l - 3-4 weekly

- Causes a lot of issues - severe iron overload, diabetes and thyroid problems, liver cirrhosis

Question 23

Thalassaemia Intermedia

Answer 23

• term for mild forms of the conditions
• Don’t need transfusion
• There is RBC break down mostly in bone marrow which is irritant to vascular endothelium = constriction = pulmonary hypertension

Question 24

Hb type and rate rule for sickle + thalassaemia

Answer 24

• Sickle cell disease = abnormal Hb produced at normal rate

- Thalassaemia = normal Hb produced at abnormal rate – but the RBC may be affected by the change in Hb