HERIDITARY HEMOLYTIC ANEMIAS (INTRACORPUSCULAR)

Dr Vijay Shankar . S

ABNORMALITIES OF RED CELL MEMBRANE

Heriditary spherocytosis

Heriditary elliptocytosis

Introduction Common type of heriditary

hemolytic anemia. Autosomal dominant inheritance

(75%) Autosomal recessive(25%). Red cell membrane is abnormal.

Pathophysiology

Defect in the proteins which anchor the lipid bilayer with the underlying cytoskeleton.

1. Defect in the Spectrin2. Defect in the Ankyrin

These defects results in unstable membrane but with normal volume.

They lose membrane further when in the circulation

Assume Spheroidal shape and smaller size

Microspherocytes

Reduced cellular flexibility

Destroyed in the spleen

Clinical features May be clinically apparent at any age

from infancy to old age Equal sex incidence Family history may be present1. Anemia – mild to moderate degree2. Splenomagaly3. Jaundice4. Pigment gallstones

Lab findings Anemia – mild to mederate degree Reticulocytosis Blood film show characteristic

MICROSPHEROCYTES. MCV is normal or slightly decreased MCHC is increased

MICROSPHEROCYTES

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

Osmotic fragility test is INCREASED

Direct Coombs test is NEGATIVE

Cholelithiasis occurs in 40 to 50% of the affected adults.

Moderate splenic enlargement is seen.

HEMOLYTIC DEFECTS DUE TO ENZYME DEFICIENCY

G6PD Deficiency. PK deficiency

PATHWAYS OF METABOLOSM IN ERYTHROCYTE

H M P SHUNT

G6PD DEFICIENCY Most common human enzyme

deficiency in the world X linked trait affecting males. females are carriers.

Patients with G^PD deficiency develop hemolytic anemia when they are exposed to oxidant stress like

1. Viral and bacterial infections2. Drugs( antimalarials,

sulfonamides , aspirin, vit K)3. Metabolic acidosis4. Ingestion of Fava beans ( Favism)

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.

Lab findings During the period of acute

hemolysis1. Fall in hematocrit.2. Features of intravascular hemolysis3. Formation of Heinz bodies seen in

supravital stain

e Between the crisis

1. red cell survival is shortened.

DIAGNOSIS – by direct enzyme assay

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.

Summary

Thank you