Haemoglobinopathies and Obstetric Haematology Flashcards
Antenatal Haemoglobinopathy screening
- Family origin + FBC
- Partner testing
Postnatal Haemoglobinopathy screening
- Newborn screening at 5 days
- Heel prick test - analysis of dried blood spot
Physiological macrocytic anaemia - changes in pregnancy
- Plasma volume expands by 50%
- RBC mass increases
- Haemodilution occurs, maximally at 32 weeks
Leucocytosis - changes in pregnancy
- 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
Gestational thrombocytopenia - changes in pregnancy
- Platelet count falls after 20 weeks and thrombocytopenia is most marked in late pregnancy
- Usually resolves after pregnancy
Coagulation - changes in pregnancy
- pregnancy is a pro-thrombotic state
- Evidence of platelet activation
- Increase in plasma fibrinogen
Haemoglobinopathies
- Changes in globin genes
- AR inheritance
- Single point mutations cause structural Hb variants - HbS (sickle)
Sickle cell Disease cause
- Substitution of valine for glutamic acid in position 6 in the beta globin chain results in a HbS
Heterozygous (HbA/HbS)
- HbS 45%, HbA 55%
- No problems except when extreme hypoxia/dehydration
Homozygous (HbS/HbS)
- 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
Acute complications of Sickle cell
- Vaso-occlusive crisis – inflammation of hands/feet
- septicaemia
- sequestration crisis (obstruction of spleen/liver - jaundice)
Chronic complications of Sickle cell
- Hyposplenism - more prone to sepsis
- Renal disease - tubular damage, chronic renal failure
- Avascular necrosis - femoral/humeral heads
Treatment of sickle cell
- Penicillin from 6 months
- Vaso-occlusive – analgesia (opiates), hydration, treatment of precipitants
- Hydroxycarbamide – increases HbF
- Transfusion
Thalassaemia
- 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
Alpha thalassaemia
- 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)
Beta thalassaemia
- Reduced rate of production of beta-globin chains
- Blood picture resembles iron deficiency
- Total Hb level is normal or slightly reduced
hydrops fetalis
abnormal accumulation of fluid in two/+ foetal compartments; survives few months and foetus dies invitro due to heart failure due to severe anaemia
How many genes code for the alpha chain
4
How many genes code for the beta chain
2
Beta thalassaemia major
- 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
Clinical features of Beta thalassaemia major
- 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
Treatment of thalassaemia
- 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
Thalassaemia Intermedia
- 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
Hb type and rate rule for sickle + thalassaemia
- 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
