This document summarizes hereditary hemolytic anemias caused by abnormalities in the red blood cell membrane, specifically hereditary spherocytosis and elliptocytosis. It describes the pathophysiology as defects in membrane proteins like spectrin or ankyrin that cause unstable membranes. Clinical features include anemia, splenomegaly, jaundice and gallstones. Laboratory findings show microspherocytes on blood smear and increased osmotic fragility. G6PD deficiency and pyruvate kinase deficiency are also summarized as enzymatic causes of hemolytic anemia that present with hemolysis when exposed to oxidative stress or inability to generate ATP respectively.

1. HERIDITARY HEMOLYTIC
ANEMIAS
(INTRACORPUSCULAR)
Dr Vijay Shankar . S

2. ABNORMALITIES OF
RED CELL
MEMBRANE
Heriditary spherocytosis
Heriditary elliptocytosis

3. Introduction
 Common type of heriditary hemolytic anemia.
 Autosomal dominant inheritance (75%)
 Autosomal recessive(25%).
 Red cell membrane is abnormal.

5. Pathophysiology
 Defect in the proteins which anchor the lipid
bilayer with the underlying cytoskeleton.
1. Defect in the Spectrin
2. Defect in the Ankyrin
These defects results in unstable membrane but
with normal volume.

6.  They lose membrane further when in the
circulation
Assume Spheroidal shape and smaller size
Microspherocytes
Reduced cellular
flexibility
Destroyed in the spleen

8. Clinical features
 May be clinically apparent at any age from infancy to
old age
 Equal sex incidence
 Family history may be present
1. Anemia – mild to moderate degree
2. Splenomagaly
3. Jaundice
4. Pigment gallstones

9. Lab findings
 Anemia – mild to mederate degree
 Reticulocytosis
 Blood film show characteristic
MICROSPHEROCYTES.
 MCV is normal or slightly decreased
 MCHC is increased

10. MICROSPHEROCYTES

13. Osmotic fragility test
 Principal confirmation test for the diagnosis of
HS
 This test is a measure of erythrocyte’s resistance
to hemolysis by osmotic stress which depends
primarily on
 Volume of the cell
 The surface area
 Membrane function

14.  Osmotic fragility test is INCREASED

15.  Direct Coombs test is NEGATIVE

16.  Cholelithiasis occurs in 40 to 50% of the
affected adults.
 Moderate splenic enlargement is seen.

17. HEMOLYTIC DEFECTS DUE TO
ENZYME DEFICIENCY
 G6PD Deficiency.
 PK deficiency

18. PATHWAYS OF METABOLOSM IN ERYTHROCYTE

19. H M P SHUNT

20. G6PD DEFICIENCY
 Most common human enzyme deficiency in the
world
 X linked trait affecting males.
 females are carriers.

21.  Patients with G^PD deficiency develop
hemolytic anemia when they are exposed to
oxidant stress like
1. Viral and bacterial infections
2. Drugs( antimalarials, sulfonamides , aspirin, vit
K)
3. Metabolic acidosis
4. Ingestion of Fava beans ( Favism)

22. Clinical features
 That of acute hemolytic anemia within hours of
exposure to oxidant stress.
 self limited since it affects the older cells only.
 some patients have darkening of urine due to
hemoglobinuria
 More severe cases present with jaundice.

23. Lab findings
 During the period of acute hemolysis
1. Fall in hematocrit.
2. Features of intravascular hemolysis
3. Formation of Heinz bodies seen in supravital
stain

25. e
 Between the crisis
1. red cell survival is shortened.
DIAGNOSIS – by direct enzyme assay

26. PYRUVATE KINASE
DEFICIENCY
 Rare
 Red cells are unable to generate ATP for red cell
membrane function.
 The result is rigid inflexible cells that are
sequestered by the spleen and hemolyzed
 Both sexes are affected
 Autosomal recessive disorder.

28. Summary

29. Thank you