3: Anaemia Flashcards
Define anaemia
Reduced Hb
RBC, PVC/Hct usually also reduced
Mechanisms and causes of Microcytic anaemia
Defect in haem synthesis: Iron deficiency, anaemia of chronic disease
Defect in globin synthesis: alpha/beta thalassaemia (affecting alpha/beta globin chains)
Mechanisms and causes of Macrocytic anaemia
- Megaloblastic anaemia due to lack of vit B12 or folic acid
- Use of drugs interfering with DNA synthesis
- Liver disease/ethanol toxicity
- Increase in reticulocytes (young red cells) which are 20% bigger than normal - recent blood loss with adequate iron stores, haemolytic anaemia
Mechanisms and causes of Normocytic Normochromic anaemia
- Recent blood loss - trauma, peptic ulcer
- Failure of production of red cells - early stages of iron deficiency/anaemia of chronic disease, renal failure (less erythropoietin), bone marrow failure
- Pooling of red cells in spleen - hypersplenism
Define haemolytic anaemia
Anaemia resulting from shortened survival of red cells
Classifications of haemolytic anaemia
Inherited haemolytic anaemia = result of intrinsic cell abnormalities in cell membrane, Hb or enzymes
Acquired haemolytic anaemia = result of extrinsic factors (e.g. micro-organisms, chemicals, drugs) that damage the red cell
Intravascular haemolysis = when there is very acute damage to red cell
Extravascular haemolysis = when defective red cells are removed by spleen
When do you suspect haemolytic anaemia
- Otherwise unexplained normochromic normocytic/macrocytic anaemia
- Evidence of morphologically abnormal red cells (including polychromia)
- Evidence of increased red cell breakdown
- Evidence of increased bone marrow activity
Clinical signs: jaundice, gall stones?
Give examples of inherited haemolytic anaemias and their site of defects
- Hereditary spherocytosis - Membrane
- Sickle cell anaemia - Haemoglobin S
- Glucose-6-phosphate Dehydrogenase deficiency - pentose shunt
Give examples of acquired haemolytic anaemias and their site of defects
- Autoimmune haemolytic anaemia - Membrane
- Microangiopathic haemolytic anaemia - whole red cell
- Malaria - whole cell
- Drugs/chemicals (oxidants) - whole cell
What is Hereditary spherocytosis?
How does the bone marrow respond?
Inherited INTRINSIC defect of red cell membrane
Loses membrane in the spleen and becomes spherocytic
EXTRAVASCULAR haemolysis - removed prematurely by spleen
Bone marrow responds by increasing output of red cells - leads to polychromasia and reticulocytosis
What clinical symptoms does haemolysis result in?
Jaundice, increased bilirubin production and gallstones
How do you treat hereditary spherocytosis
Splenectomy (but only in severe cases)
Prevent secondary folic acid deficiency - good diet and/or folic acid tablets
What is G6PD deficiency? How does it cause haemolytic anaemia? Treatment?
G6PD important for protection of red cell from OXIDANT damage
Involved in pentose phosphate shunt
Causes severe intermittent INTRAVASCULAR haemolysis due to infection or exposure to exogenous oxidants
Hb denatures and forms Heinz bodies which are removed by spleen, forming lots of irregularly contracted cells
Severe haemolysis may need blood transfusion
What is the mechanism of autoimmune haemolytic anaemia?
Autoantibodies bind to red cell antigens
Antibodies/complements bound to red cells are detected by splenic macrophages which remove parts of membrane, causing spherocytosis
Spherocyte rigidity + antibody detection lead to removal of red cells by spleen (extravascular haemolysis)
How might you diagnose autoimmune haemolytic anaemia?
- Find spherocytes and increased reticulocyte count
- Detect immunoglobulin/complement on red cell
- Detect antibodies for red cell in the plasma
