Haem 3 - Anaemia and Polycythaemia Flashcards
What is anaemia
Reduction in amount of Hb in given volume of blood (below what would be normal for same age and gender healthy subject)
Hb reduced, usually RBC & PCV/Hct reduced too
It can be from increase in plasma volume though usually due to reduction in absolute amount of Hb
What are the mechanisms of anaemia
- Reduced production of RBC/Hb in bone marrow
- Loss of blood from body
- Reduced survival of RBCs in circulation
- Pooling of RBC in very large spleen
How can anaemia be classified based on cell size
- Microcytic (usually also hypo chromic)
- Normocytic (usually normochromic)
- Macrocytic (normochromic)
What are the causes of microcytic anaemia
- Defect in haem synthesis due to iron deficiency or anaemia of chronic disease (e.g. Rheumatoid arthritis)
- Defect in global synthesis (thalassaemia) caused by defect in a-chain synthesis or b-chain synthesis
How is macrocytic anaemia usually caused
Macrocytic anaemia usually due to abnormal haemopoiesis —> RBC precursors continue to synthesise Hb and other cellular proteins —> fail to divide normally
Megaloblastic erythropoiesis can cause macrocytic anaemia. How?
Delay in maturation of nucleus - whilst cytoplasm continues to grow.
What is a megaloblast
Abnormal bone marrow erythroblast –> larger than normal and shows nuclei-cytoplasmic dissociation
What is an alternative mechanism of macrocytosis
Premature release of cells from bone marrow (increased reticulocyte)
Reticulocyte = 20% larger than mature RBC
Megaloblastic anaemia - causes
- Lack of Vit B12 / folic acid
What are the common causes of macrocytic anaemia
- Megaloblastic anaemia - lack of Vit B12 / folic acid
- Drugs interfering with DNA synthesis
- Liver disease and ethanol toxicity
- Major blood loss (with adequate iron stores)
- Haemolytic anaemia
What are the mechanisms of normocytic normochromic anaemia
- Recent blood loss
- Failure of production of RBC
- Pooling of RBC in spleen
What are the causes of normocytic normochromic anaemia
- Peptic ulcer, oesophageal varices, trauma
- Failure of production of RBC (e.g. due to renal failure / bone marrow failure or suppression)
- Hypersplenism e.g. portal cirrhosis
What is haemolytic anaemia
Anaemia resulting from shortened survival of RBC in circulation
Can result from intrinsic abnormality of RBC, or extrinsic factors acting on normal RBC
Haemolytic anaemia can be classified as inherited or acquired - describe each
Inherited haemolytic anaemia = abnormalities in cell membrane/Hb/enzymes in red cell
Acquired haemolytic anaemia = extrinsic factors (Eg microorganisms, chemicals, drugs) that damage red cell
(extrinsic factors can also interact with RBCs that have intrinsic abnormality)
Haemolytic anaemia can be classified as intravascular or extravascular. Describe each
Intravascular haemolysis = very acute damage to the red cell
Extravascular haemolysis = when defective red cells are removed by spleen
Often mixture of intravascular and extravascular
Sickle cell lifespan = 20 days. Normal RBC lifespan =?
120
What are inherited forms/causes of haemolytic anaemia
- Abnormal RBC membrane - hereditary spherocytosis
- Abnormal Hb - Sickle cell anaemia
- Defect in glycolytic pathway (e.g. pyruvate kinase deficiency)
- Defect in enzymes of pentose shunt (e.g. G6PD deficiency)
What are acquired forms/causes of haemolytic anaemia
- Damage to RBC membrane (AIHA / snake bite)
- Damage to whole RBC (MAHA)
- Oxidant exposure/damage to RBC membrane and Hb (e.g. dapsone or primaquine)
NB- Primaquine/dapsone combined with defective Pentose shunt enzymes (G6PD deficiency - inherited) is a precipitation of episodic acute haemolytic - this is a combination of extrinsic and inherited conditions in tandem
When should we suspect haemolytic anaemia
Normochromic anaemia, either normocytic or microcytic - no other explanations
Evidence of morphologically abnormal RBC
Evidence of increased RBC breakdown
Evidence of increased bone marrow (also lactate dehydrogenase increased)
Describe hereditary spherocytosis
Haemolytic anaemia or chronic compensated haemolysis - resulting from inherited intrinsic defect of RBC membrane
After entering circulation, cells lose membrane in the spleen - become spherocytic
Spherocytic RBC = less flexible and removed prematurely by spleen (extravascular haemolysis)
What happens if extravascular haemolysis occurs as a result of hereditary spherocytosis
Bone marrow increases RBC output - leading to polychromasia + reticulocytosis
Haemolysis leads to increased bilirubin production, jaundice and gallstones
How is hereditary spherocytosis treated
Only effective treatment = splenectomy (but has own risks so only done in emergency)
Good diet important to prevent secondary folic acid deficiency - may also take a folic acid tablet daily
What is G6PD
G6PD deficiency = intravascular haemolysis
Glucose-6-Phosphate Dehydrogenase
Important enzyme in pentose phosphate shunt - essential to protect RBC from oxidant damage
(Oxidants may be generated in bloodstream (e.g. during infection) or may be exogenous)
What extrinsic oxidants may exacerbate a G6PD deficiency
Foodstuffs (broad beans), chemicals, drugs
G6PD gene is on X Chr - usually hemizygous males affected (but sometimes homozygous females)
How does G6PD deficiency show
Associated with appearance of irregularly contracted cells
Hb denatured and forms round inclusions - Heinz bodies
What is one way to treat acute haemolysis
Blood transfusion
Describe autoimmune haemolytic anaemia
Production of auto-antibodies - directed at RBC antigens
Ig bound to RBC is recognised by splenic macrophages - this results in spherocytosis as part of the RBC cell membrane are removed
(Complement that is bound to Ig can also be recognised)
How is autoimmune haemolytic anaemia diagnosed
Diagnosis by:
- Finding spherocytes and increased reticulocyte count
- Detecting Ig + complement on RBC surface
- Detecting antibodies to RBC antigens / other autoantibodies in the plasma
How is autoimmune haemolytic anaemia treated
- Corticosteroids and immunosuppressive agents
2. Splenectomy if severe cases
How is microangiopathic haemolytic anaemia treated
- Removing the cause (e.g. treating hypertension or stopping causative drug)
- Plasma exchange when it is caused by an antibody that leads to fibrin deposition
Microcytic anaemia is likely to be due to?
Iron deficiency
Polycythaemic patient with Red urine. Most likely due to?
Renal carcinoma
Haemoglobinuria indicated haemolysis
Polycythaemia rules out haemolysis
Haematuria = RBC in urine
Haemoglobinuria = Hb in urine
