hematology

Haemolytic Anaemias

Haemolysis: Shortening of red cell survival with premature red cell death. When the life span of the red cells is shortened to less than 20 days, Hb drops and anaemia develops (Haemolytic anaemia ), with longer life spans the marrow can compensate by hyperactivity &/or expansion keeping Hb within normal limits (Compensated haemolysis )

Classification

H. Anaemias due to intrinsic red cell defects ( usually inherited ) Red cell membrane defects ( e.g H.Spherocytosis) Metabolic defects ( Enzymopathies, e.g G6PD deficiency) Hb synthesis defects ( haemoglobinopathies ) H. Anaemias due to extrinsic defects: Immune H. Anaemias Mechanical H. Anaemias. H. Anaemias due to Infections, Chemical toxins and Physical agents. Haemolysis is called intravascular when RBCs are destroyed in the circulation, while it is called extravascular when destruction occurs by the cells of the RES in the spleen, liver & B.M

General Features of Haemolysis

Features due to Hb degradation: Indirect hyperbilirubinaemia ( clinically; Jaundice, gall stones ) Hyperurobilinogenuria RES hyperplasia ( clinically; splenomegaly ) Iron overload Featurs due to marrow compensation: Reticulocytosis Skeletal abnormalities due to marrow expansion. Folate deficiency. Features specific of intravascular haemolysis: Haemoglobinaemia & hypohaptoglobinaemia. Haemoglobin & haemosiderinuria.

Hereditary Spherocytisis ) HS )

A hereditary haematological disorder characterized by: Autosomal dominant inheritance. Excessive red cell fragility. Microspherocytes in the peripheral blood. Marked improvement ( usually cure ) of anaemia after splenectomy.

Molecular defects and pathogenesis

A genetic mutation resulting in abnormality of the cytoskeletal protein; spectrin will cause excessive leakiness of the cell membrane to cat-ions (Na & K ) »» Hyperactivity of Na-K pump »» excessine utilization of glucose & O2 ( hypermetabolism )….. In the spleen where there is stagnation, hypoxia, hypoglycaemia and acidosis »» Failure of Na-K pump »» Entry to the cell of Na with water »» swelling of the cell »» Spherocytosis »» further stagnation »» loss of cell membrane »» rupture ( haemolysis ) and microspherocyte formation

Haematological Featurs

Anaemia; normochromic normocytic with spherocytosis Reticulocytosis Increased red cell fragility


Diagnosis
Jaundice, anaemia, splenomegaly. Positive family history, lab evidence among other members. Spherocytosis with reticulocytosis Increased red cell fragility Cure of anaemia after splenectomy

G6PD Deficiency

G6PD normally provides reducing potentials through the production of NADPH during the conversion of G6P to 6PG in the pentose pathway. NADPH neutralizes the effects of H2O2 & other oxidants by reducing them to water. Accumulation of intracellular oxidants will damage the cell through: Perroxidation of membrane lipids. Denaturation of Hb with Heinz body formation.

Molecular defects and pathogenesis

G6PD deficiency results from point mutations affecting G6PD gene on chromosome – X, mutations will result in isoenzymes that are either:Unstable.Reduced catalytic function.The pathological effects of the deficiency depends on the residual activity of the enzyme:Activities of >3-5% normal are sufficient to maintain normal red cell metabolism under normal conditions but will lead to intravascular haemolysis under conditions of extr-oxidant stresses ( infections, drugs & ingestion of fava beans ).Activities lower than 3% are associated with chronic haemolysis.

Clinical presentation

Neonatal jaundice Chronic haemolytic anaemia ( rare presentation ) Most individuals with G6PD deficiency are asymptomatic unless exposed to oxidant stresses, such as infections, drugs and fava beans ingestion, the latter is called Favisim where there will be a sudden bout of intravascular haemolysis characterized by: Abdomenal pain, rigors, back pain and vomiting. Rapidly deepenig pallor. Passage of red urine ( Hb-uria ) Jaundice Patient may pass into shock and renal failure.

Haematological features

Normoch. Normocytic anaemia with contracted &blister cells. Heinz bodies formation. Marked reticulocytosis. haemoglobinaemia, & Hb-uria. Indirect hyperbilirubinaemia.

Diagnosis

Typical clinical picture of sudden bout of intravascular haemolysis uppon ingestion of broad beans, drugs or after infection. Haematological features of acute intravascular haemolysis. Demonstration of G6PD deficiency: Screening tests ( MRT) Enzyme assay.