Haemolytic anaemia results from an increase in the rate of red cell destruction.
The lifespan of normal RBC is 100-120 days. Red cells are destroyed or broken down at a rate higher than the marrow can compensate by producing new red blood cells. (normally marrow has a capacity to increase red blood cells production about 4 times of normal.)
In haemolytic anaemia the rate of destruction is so high that marrow can't replace the destroyed red blood cells even by increasing red blood cells production.
Causes of haemolytic anaemias:
1Production of defective red blood cells/inherent defect in the RBC/Intrinsic defect:
Congenital defects:
Defects in the membrane of the red blood cells:
-Hereditary spherocytosis
-Hereditary elliptocytosis
-Hereditary xerocytosis and hydrocytosis.
Enzyme deficiencies:
Non-spherocytic congenital haemolytic anaemias.
-Deficiency of glucose -6 phosphate dehydroginase (G 6 P D)
-Deficiency of pyruvate kinase (PK)
Drug induced haemolytic anaemia and favism
Defect in the formation of hemoglobin:
Thalassaemias:
Failure to form normal amount of globin chain or
Production of less amount of normal globin chains.eg. a thalassaemia and b thalassaemia.
Haemoglobinopathies:
Formation of abnormal globin chains. ( sickle cell anaemia, Hb-C, Hb-E, Hb-D disease.)
Double heterogygous disorders:
Sickle cell b thallasaemia.
Acquired defects:
-Paroxysmal nocturnal haemoglobinuria
uDefect in the environment of the red cell/ defect in the plasma (Extrinsic defect, extracorpuscular defect)
Haemolytic agents (antibodies) present in the plasma :
-autoimmune acquired haemolytic anaemias: warm antibody
cold antibody
-Haemolytic diseases of newborn ( Rh incompitability, ABO incompitability)
-Incompitable blood transfusion.
-Drug induced haemolytic anaemias.
Traumatic/mechanical hemolytic anaemia:
-Cardiac prosthetic haemolytic anaemia
-Microangiopathic haemolytic anaemia
-March haemoglobinuria.
Other causes:
-Haemolytic anaemia due to direct effects of chemicals and drugs, toxins (Cl welchi) on red blood cells.
-Haemolysis due to infection (septecemia due to strepto beta haemolyticus);Malaria
-Haemolytic anaemia due to burn
-Lead poisoning.
Haemolytic anaemia due to extra corpuscular mechanisms:
Acquired:
Immune mechanisms
Auto-immune acquired haemolytic amaemia
Haemolytic diseases of the newborn
Incompatible blood transfusion
Drug induced haemolytic anaemia.
Non-immune mechanisms
Mechanical haemolytic anaemia:
Cardiac haemolytic anaemia
Micro-angiopathic haemolytic anaemia
March haemoglobinuria
Miscellenious:
Haemolytic anaemia due to direct action of chemicals and drugs.
HA due to infection
HA due to burns
Lead poisoning.
Investigations of haemolytic anaemia:
Estimation of Hb:
For determining the severity of haemolysis and its use as reference if haemolysis is progessing, persistent and has ceased.
Evidence of haemolysis:
Blood film- Red cells marked anisocytosis and polychromasia;
Sperocytotes and fragmented red cells.
Heinz bodies, macrocytes
Nucleated red cells may be seen.
Mild leucocytosis and thrombocytosis is usual.
Reticulocytes increased.
Hyperbillirubinaemia-
Increased serum bilirubin ( normal conc 0.2-0.8mg/dl). Amount depends on the severity of haemolysis;
In Rh incompitability in the new born serum bilirubin may exceed 20mg/dl
Increased urobillinogen excretion in the urine.
Increased red cell fragility:
Decreased red cells resistance to graded sodium chloride solution (fragility test).
In the normal persons red blood cells show haemolysis starting at sodium chloride conc. Of 0.4% and complete haemolysis at 0.2% sodium chloride strength.
In the haemolytic anaemias red blood cells show haemolysis at higher Nacl strength i.e haemolysis start at 0.65% and completes at 0.45%.
Investigations:
Hb is usually 7-14g/dl but may fall below 7g/dl during crisis.
MCV usually normal but is occassionally slightly reduced.
MCH is normal but MCHC is often increased.
Reticulocytes commonly ranges from 5-20%.
Peripheral blood film:
Spherocytes are usually numerous
osmotic fragility test:
The red cell osmotic fragility of blood is increased
Serum billirubin level:
Serum billirubin usually lies between 17and 70mmol/l
Clinical features:
Are similar to acute hemolytic anaemia.
Severity of hemolytic episode induced by a particular drugs, related to dosages.
Primaquine-sensitive blacks volunteers, receiving 30mg primaquinine per day
This results in a self limiting haemolysis, commencing in 2-3 days and lasting for about 7 days and followed by a return of Hb value to normal after 20-30 days despite continued drug administration.
Clinically some pt have only darkening of urine, but the more severely affected pt complain of constitutional symptoms and jaundice.
The self limiting nature of haemolysis is because red cell drug sensitivity is a function of cell age; older cells are destroyed, while younger cells are resistant.
Haemolysis stop and Hb return to normal when older cells are destroyed and only the younger cells remain.
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