at the end of this lecture you will learn:
Hereditary spherocytosis: characteristics, pathogenesis, and clinical features.
G6PD deficiency: definition, clinical and hematological features, and diagnosis.
Hereditary Spherocytosis ) HS )
hereditary disorder characterized by:
Autosomal dominant inheritance ,few recessive and others may be due to new mutation.
The morphologic hallmark of HS is the Microspherocyte in the peripheral blood , which is less flexible than normal RBC.
Clinically, HS can vary from mild to severe anemia. most individuals with HS have moderate disease. Patients with severe cases may present in early childhood. In mild cases it may go unnoticed until adulthood.
Marked improvement after splenectomy.
Molecular defects and pathogenesis
In HS, intrinsic defects in erythrocyte membrane proteins result in RBC cytoskeleton instability. spectrin deficiency is the most common defect in HS. Spectrin normally will cause excessive leakiness of the cell membrane to cat-ions (Na & K ) »» Hyperactivity of Na-K pump »» excessive utilization of glucose & O2 ( hypermetabolism )….. In the spleen there is stagnation, hypoxia,acidosis and hypoglycaemia » 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
Diagnosis
Positive family history.
Clinically: anemia, jaundice and splenomegaly. In newborns jaundice is the most common symptom rather than anemia.
Hematological features: normochromic normocytic anemia, reticulocytosis, spherocytosis, and increase red cell fragility.
Specific diagnostic tests: osmotic fragility test, flow cytometric analysis and acidified glycerol lysis test.
G6PD deficiency
G6PD deficiency is an x- linked inherited disease.
The G6PD enzyme is part of pentose pathway, it catalyzes the oxidation of glucose-6-phosphate and the reduction of (NADP+) to (NADPH).
NADPH maintains glutathione in its reduced form, which neutralize the effect of dangerous oxidants.
In G6PD deficiency, oxidative stresses can denature hemoglobin and cause intravascular hemolysis.
Denatured hemoglobin can be visualized as Heinz bodies in peripheral blood.
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
Normochromic Normocytic anemia 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) MetHB reduction test
or flourescence test
Enzyme assay.
