Haemoglobinopathies and obstetric haematology Flashcards
What is RBC production controlled by?
EPO produced in the kidney
What is Hb comprised of?
Central harm group
2 alpha and 2 non-alpha chains (beta, delta, gamma)
Name the different types of Hb in a normal adult.
Hb-A - 2 alpha/2 beta
Hb-A2 2 alpha/2 delta
Hb- fetes - 2 alpha/2 gamma
What are the two ways in which haemoglobinopathies arise?
Structural HB variants e.g. Hb S - single base substitution in global gene (altered function/structure)
Thalassaemias (alpha or beta) - reduce synthesis of normal global chain. Imbalance of alpha and beta chain production
What maternal testing is performed in predicting fatal haemoglobinopathies/thalassaemia?
-genetic screening/counselling
Prenatal testing - chorionic villus biopsy and genetic diagnosis
Termination of affected pregnancy
Pregnant women usually have physiological anaemia. Why?
Haemodilation
- plasma volume increases by 50% while RBC volume only by 25%
Describe the changes that occur in haematological values in pregnancy
MCV increases - size of RBC - increased mobilisation of vit and mineral stores
Leucocytosis - neutrophilia (left shift)
Thrombocytopenia
Pregnancy = pro-thrombotic state (decreased fibrinolysis)
Anaemia
How are haemoglobinopathies diagnosed?
FBC/FIlm
Haemoglobin electrophoresis
What differences do we observe in film/Hb electrophoresis in individuals with structural Hb variants or with thalassaemia?
Strutural Hb variants - Hb electrophoresis identifies differences, sickled cell present on film
Thalassaemia - not observed in electrophoresis but in film, pale and small (microcytic/hypochromic)
What is sickle cell disease cause by? i.e. genetic basis
Hb S - valine substitution for glutamine at position 6 on the Beta globin gene
What type of anaemia is sickle cell anaemia?
Haemolytic - shorter lifespan - 10-20 days - release of Hb - irritant to vessels - inflammation and vasoconstriction
What do sickled RBCs do?
At low oxygen tensions, Hb-s polymerise, forming tactoids which distort red blood cell - stick together and obstruct vessel - ischaemic damage
What are the features (i.e. blood count, ratio of HbS:HbA, and clinical features) of heterozygous Hb (sickle cell TRAIT)?
HbS/HbA
Blood count = normal
Electrophoreses = HbS = 45%, HbA = 55%
Clinical features - normal except in extreme hypoxia/dehydration
What are the features (i.e. blood count, ratio of HbS:HbA, and clinical features) of homozygous Hb (sickle cell DISEASE)?
HbS/HbS
- Blood count:anaemia (60-80g/L)
- Blood film: sickle cells
Hb electrophoresis: HbS = 95% HbA= 0%)
hat are the acute complications of sickle cell disease?
Vado-Occlusive crisis - chest, bone, abdomen, brain, priapism (painful penis erection)
- Septicaemia
- Aplastic crisis
- Sequestration crisis (spleen,liver)
What are the chronic complications of sickle cell disease?
- retinopathy
- Acute resp syndrome
Haematuria and polyuria - infections/autosplenectomy
- Avascular necrosis of long bones
- leg ulcers
- anaemia
- Jaundice and gallstones
What is the treatment for sickle cell disease?
- Avoidance of precipitating factors of crises e.g. hypoxia/dehydration
- penecillin prophylaxis from 6 months
- RBC exchange transfusion - reduce Sickle cells
- pain management of crises (analgesics/opiates)
- Hydroxycarbamide increases-
HbF. It reduces the tendency to acute sickle crises
Broadly, what is thalassaemia?
- NOT structural abnormality
- synthesis of one of the global chains (Alpha/beta) is reduced
Chains are either ABSENT or synthesised at REDUCED rate
What syndromes are associated with Alpha thalassaemia?
Hb Barts (4 gamma Hb) Hydrops fetalis - death in utero
HbH (tetramers 4 beta chains) - moderate microcytic,hypochromic anaemia
alpha trait - alpha plus (2x alpha nots and 2 aplha+) - no clinical consequences
What is Beta thalassaemia? What are the two types?
Reduced rate of production of beta-globing chains (excess alpha chains)
-Thalassaemia minor - clinically normal
Thalassaemia intermedia - between mild and severe
Thalassaemia major - severe disease - can produce very little, if any, HbA
What is the clinical diagnosis of an individual with beta thalassaemia intermedia?
Someone with a Hb level of 60-70g/L without need for blood transfusions
What are the clinical features of beta thalassaemia minor?
Microcytic and hypo chromic cells (resembles iron deficiency)
Total Hb level normal/slightly reduced
No clinical problems
HbA2 level > 3.5%
What are the clinical features of beta thalassaemia major?
Severe anaemia from a young age
Severe microcytic, hypochromic anaemia
Hb 30-60 g/L
Abnormal blood film with nucleated RBCs
What are the symptoms of Beta thalassaemia major related to?
Symptoms related to severe anaemia and body’s increased production of RBCs to compensate
