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
What are the pathological features of beta thalassaemia major?
Defective Hb synthesis and haemolysis results in…
Increased bone marrow activity and bone marrow expansion to increase production - skeletal deformity and stunted growth
- Iron overload - (secondary to blood transfusion) damage organs and endocrine systems
- protein malnutrition
- Splenomegaly and hepatomegaly “extra medullary haemopoises”
What signs are characteristic of beta thalassaemia major?
Thalassaemia faces
‘Hair on end’ X-ray, frontal bossing, maxillary hypertrophy
Due to expanded bone marrow
What is the treatment for beta thalassaemia major?
Transfusion - maintain Hb 120 g/L to prevent excessive bone marrow RBC production (stops skeletal deformity and hepatosplenomegaly)
Iron chelation therapy
Bone marrow transplantation has been curative!
What is the problem of blood transfusions in the treatment of beta thalassaemia major?
Iron overload - body has no mechanism to excrete iron
Gonad/hypothalamus - failure of puberty, growth failure
Liver - cirrhosis
Pancreas - diabetes
Heart - cardiomyopathy and heart failure
What are the two iron chelation drugs?
DeFERIprone and deFERAsirox
