39 - Obstetric Haemoglobinopathy Flashcards
Haemoglobinopathies
Structural Hb Variants
Thalassaemias (alpha or beta)
Structural Hb Variants
Hb S, C, D, E
Single base sub in globin gene -> altered structure/function
Thalassaemias
Change in globin gene expression leads to reduced rate of synthesis of normal globin chains
Imbalance of alpha and beta chain production
Anaemia in pregnancy
Plasma volume expands in pregnancy by 50%
Red cell mass expands by 25%
Haemodilation occurs - max at 32 weeks
MCV increases physiologically in pregnancy
What affect does MCV increase have in pregnant women?
Increases iron requirements
Results in mobilisation of Fe stores
Increases folic acid requirements
Another physiological change in blood in pregnancy
Leukocytosis
Peaks in 2nd and 3rd trimester
Gestational thrombocytopenia
Platelet count usually >70x10^9/l
Platelet count falls after 20 weeks and thrombocytopenia is most marked in late pregnancy
No clinical significance
Recovers rapidly
Causes of thrombocytopenia in pregnancy
Pregnancy related = production failure (folate), consumptive
Coincidental = production failure, consumptive (sepsis, viral, type 2B vWD), congenital
Pro-thrombotic state in pregnancy physiological explanation
Platelet activation Increase in procoagulant factors Reduction in natural anticoagulants Reduction in fibrinolysis Rise in markers of thrombin generation
Diagnosis of haemoglobinopathies
Structural Hb variants detected via Hb electrophoresis
Results of Hb electrophoresis
Thalassaemias have normal Hb electrophoresis
Small pale red cells resemble iron deficiency
Heterozygous sickle cell anaemia - Investigation results
Normal blood film
Hb-S 45%
Hb-A 55%
Heterozygous sickle cell anaemia - clinical presentation
No problems except when extreme hypoxia/dehydration
Homozygous sickle cell anaemia - investigation results
Anaemia - Hb 6-8g/dl
Blood film shows sickle cells
Hb-S >95% Hb electro
Sickle cell anaemia - acute complications
Vaso-occlusive crisis - dactylitis, chest syndrome, ab (mesenteric) pain, long bone, ribs, spinal pain, priapism
Septicaemia
Aplastic crisis
Sequestration crisis
Sickle cell anaemia - chronic complications
Hyposplenism - due to infarction and atrophy of spleen
Renal disease - medullary infarction w/ papillary necrosis. Tubular necrosis (bed-wetting at night). Glomerular = chronic renal failure
Avascular necrosis - femoral/humeral heads
Leg ulcers, osteomyelitis, gall stones, retinopathy, cardiac, respiratory
Sickle cell anaemia - treatment
Penicillin from 6 months (neonatal screening)
Acute crisis managed via analgesia (opiates), hydration, treatment to precipitants
Priapism = w/ education. Acute = intracorporeal phenylephrine Recurrent = etilefrine
a-thalassaemia
Most serious - SE Asia + Mediterranean
Both Hb A and F have a-chains
Hb Barts (inheritance of a^0) = hydrops fetalis
Hb H disease
a-trait
B-thalassaemia
Reduced rate of production of beta-globin chains due to excess alpha chains
Carriers have minor disease
Homozygotes have severe which is usually fatal if untreated - produce little, if any, Hb-A and die of severe anaemia
B-thalassaemia minor - blood film resulta
Resembles iron deficiency - small, pale red cells
Thalassaemia intermedia - clinical features
no absolute requirement for regular transfusions to survive 3-5 years of life
Clinical and genetic picture highly variable
All should be genotyped
Thalassaemia intermedia - clinical presentation
Pulm. hypertension - ECHO Extramedullary haematopoiesis Bone changes and osteoporosis - DEXA Diabetes mellitis + hypothyroid Leg ulcers
B-thalassaemia major - clinical presentation
Severe anaemia at 1to2 years of ages
Abnormal blood film of nucleated RBCs
This due to bone marrow trying to make more red cells to compensate
B-thalassaemia major - pathology
Alpha chain excess
Increased marrow activity
Enlarged and overactive spleen
Alpha chain excess causes…
Ineffective erythropoiesis (red cells die in marrow) Short RBC lifespan
Which equals anaemia
Increased marrow activity…
Skeletal deformity, stunted growth
Increased iron absorption and organ damage
Protein malnutrition
Enlarged and overactive spleen…
Pooling of RBCs
Increased transfusion req.
Thalassaemic facies
Maxillary hypertrophy
Abnormal dentition
Frontal bossing due to expanded bone marrow
X-ray shows hair on end skull due to widening of diploic cavities by boe marrow expansion(can see hair follicles on X-ray)
B-thalassaemia major - treatment
Maintain mean Hb 12g/dl
Suppress marrow red cell production and prevent skeletal deformity and liver/splenic enlargement
3 to 4 weekly transfusion from 1st year of life
B-thalassaemia major - problems with transfusion treatment
Body has no excretory mechanism for iron
By 10-12 years severe iron overload
Gonads/hypothalamus - failure of puberty, growth failure
Pancreas - diabetes
Heart - dilated cardiomyopathy and heart failure
Liver- cirrhosis
How much iron is in one blood unit?
200mg iron
Other complications of transfusions
Transmission of infection
Allo-immunisation
B-thalassaemia major - treatment
Iron chelation therapy to promote excretion of iron in urine and faeces
Desferrioxamine is given 8-12 hourly subcut infusion via syringe pump as home treatment at least 5 nights a week
New oral iron chelators
Monitoring chelation - what tests
Ferratin
Liver biopsy
MRI (T2)
