39 Haemoglobinopathy + obstetric haematology Flashcards
What is the role of globin in haemoglobin? (3).
Protects haem from oxidation.
Renders molecule soluble.
Permits variation in oxygen affinity.
What type of heramoglobin does a foetus have?
Structure?
Hb-F.
2α/2γ
What types of haemoglobin are physiological in an adult? Structures?
Hb-A 2α/2β 95%
Hb-A2 2α/2δ
Simply explain the pathological basis of thalassaemias.
Change in globin gene expression leads to altered ratio of normal globin chains. Imbalance of production results in free chains which damage RBC membrane.
What types of maternal testing are available for haemoglobinopathies?
Genetic.
Antenatal screening.
When does physiological anaemia and macrocytosis occur?
When is this maximal?
Why does the MCV increase?
Pregnancy.
Plasma increases 50%, RBC increases 25%.
Haemodilution maximal at 32 weeks.
MCV increase due to Fe mobilisation.
Describe the leukocytosis seen physiologically in pregnancy:
Mainly neutrophilic - peak 9-12 in 3rd trimester.
Also left shift: myelocytes + metamomyelocytes.
When does gestational thrombocytopenia occur?
Week 20, most marked in late pregnancy.
What are the pregnancy associated causes of thrombocytopenia in pregnancy? (6).
Severe folate deficiency. Gestational. Pre-eclampisa/HELLP. AFLP (acute fatty liver of pregnancy). DIC. TTP/HUS.
What are the causes of the prothrombotic state seen in pregnancy? (4).
Platelet activation.
Increase in coagulation factors (esp fibrinogen, V, VII, VIIII, X, XII).
Decrease in fibrinolysis.
Reduction in natural anticoagulants.
What is Kleihauer testing and Supravital staining used for?
Diagnosis of haemoglobinopathies.
What is the protein change in sickle cell anaemia?
Valine substituted for glutamine at position 6 of β-globin gene.
Hb-S polymerises at low oxygen levels, distorting RBC into sickle shape.
Why is sickle cell anaemia not symptomatic for the first six months of life?
Presence of Hb-F reduced polymerisation levels.
What is the inflammatory basis of sickle cell anaemia?
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.
What is sickle cell trait?
Clinical picture?
Hb-S 45%, Hb-A 55%
No problems except in extreme hypoxia or dehydration.
What are the results of blood count and Hb electrophoresis in sickle cell disease?
Anaemia.
> 95% Hb-S.
OR βs and another β chain abnormality.
What are the acute complications of sickle cell disease? (4).
Acute vaso-occlusive crisis: priapism, chest syndrome, dactylitis.
Septicaemia.
Aplastic crisis.
Acute sequestration crisis (liver+spleen).
What are the chronic complications of sickle cell disease? (7).
Hyposplenism (infarction). Renal disease. Avascular necrosis: femoral/humeral heads. Leg ulcers Osteomyelitis Gall stones Retinopathy.
What is the treatment for sickle cell disease? (6).
Penicillin Analgesia Hydration. Transfusion top up/exchange (regular for stroke prevention). Hydroxycarbamide (increases Hb-F). Bone marrow transplant.
What is Hb Barts?
Homozygous inheritance of A0. Causes still birth.
Differentiate between thalassaemia minor and major.
Minor: carrier, clinically normal.
Major: homozygotes, in β usually fatal.
What is thalassaemia pathology due to?
α : too many β chains.
β : too many α chains.
What is the blood picture in β-thalassaemia minor? (3)
Small, pale red cells.
Slight reduction in Hb.
Increased Hb-A2 levels.
What are the complications of β-thalassaemia intermedia? (5).
Pulmonary hypertension. Extra medullary haematopoesis. Osteoporosis. DM and hypothyroidism. Leg ulcers.
What is the pathological basis of β-thalassaemia major?
Effect on bone marrow:
Effect on spleen:
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.
Describe thalassaemic facies: (3).
Maxillary hypertrophy.
Abnormal dentition.
Frontal bossing due to expanded marrow.
How is β-thalassaemia major treated?
4x weekly blood transfusion to maintain Hb and suppress marrow production/spleen enlargement.
What does iron overload cause? (4)
Growth and puberty failure.
Dilated cardiomyopathy.
Diabetes.
Liver cirrhosis.
How is death from iron overload prevented in β-thalassaemia major? (3)
Iron chelation: Desferrioxamine (IV), Deferiprone (Oral) and Deferasirox (Oral).
What is the cure rate of bone marrow translation in β-thalassaemia major?
When does it have to occur?
60-80%.
Before one year of life and iron overload.
