HEMOLYTIC ANEMIA

Normal life span of RBCs is ~120 days, except a shorter span ~60-90 days in newborns. Every day, ~1% of senescent RBCs are removed from circulation and replaced by new cells from bone marrow.

General pathophysiology: Rapid turn-over of RBCs in hemolytic anemia requires—(a) elimination of degra­dation products, and (b) compensatory increase in erythropoiesis. Bone marrow is capable to increase its output as much as by 2-3 times in acute stress and 6-8 times following chronic stress. Further increase in erythropoietic requirements necessitates reactivation of extra-medullary sites including other marrow sites, liver and spleen.

Severity of anemia in hemolytic disorders depends on severity of hemolysis as well as adequacy of compensatory erythropoiesis. However, even well compensated cases are susceptible for intermittent life-threatening aplastic crisis, usually precipitated by parvoviral infections.

General clinical picture of typical hemolytic anemia is dominated by signs of:

• Progressively severe pallor with#8725;without intermittent exacerbations.

TABLE 19.9: Classification of hemolytic anemia

• Congenital

- RBC membrane defects

#9830; Hereditary spherocytosis (commonest)

#9830; Others: H. elliptocytosis, stomatocytosis

#9830; Paroxysmal nocturnal hemoglobinuria

- RBC enzyme defects

#9830; HMPpathway: G6PD deficiency

#9830; Glycolytic pathway: Pyruvate kinase deficiency

- Hemoglobinopathies

#9830; DePcient HbA synthesis: Thalassemia

#9830; Abnormal Hb: Sickle cell anemia, Hb-C, D, E

#9830; Mixed hemoglobinopathies: Sickle thalassemia

• Acquired

- Immunological RBC injury

#9830; Iso-immunization: HDN, mismatch transfusion

#9830; Autoimmune hemolytic anemia

- Mechanical RBC injury

#9830; Direct: Malaria, infections

#9830; Sequestration: HUS, AV malformations

- Toxic or metabolic RBC injury

#9830; Acute hepatic/renal failure

#9830; Insect/snake bites, etc.

HUS: Hemocytic uremic syndrome; HMP: Hexose monophosphate; HDN: Hemolytic disease of newborn

• Compensatory erythropoiesis, e.g.

• Excessive heme degradation, e.g. icterus, gallstones, hemosiderosis, etc.

General hematological picture in hemolytic anemia is characterized by:

• Progressive drop in Hb with/without intermittent exacerbations

• High reticulocyte count due to rapid RBC turnover, appearance of immature RBCs, e.g. normoblasts, in peripheral smear along with marked anisocytosis, poikilocytosis, polychromasia and target cells, etc.

• Hypercellular bone marrow with high M:E ratio.

• Reduced survival time of radiotagged (⁵¹Cr) RBCs.

• Elevated levels of Hb degradation products, e.g. unconjugated bilirubin, iron and haptoglobins. Some common hemolytic anemias are discussed in this

chapter with greater details along with salient features of other important but uncommon disorders.

19.5.1