Two types of depletion anemia are possible: (1) abnormal loss of red blood cells (RBCs) from the circulation and (2) abnormal destruction of RBCs within the circulation. RBC loss due to hemorrhage has been covered elsewhere (blood volume, Chapter 10; iron deficiency anemia, Chapter 4). Intravascular or intrasplenic RBC destruction is called hemolytic anemia. There are two clinical varieties of hemolytic anemia. In one type, RBC destruction is relatively slow. Although RBC survival is shortened, the only laboratory test that demonstrates this fact is radioisotope study using tagged RBCs. In the other variety, hemolysis or shortened RBC life span is sufficient to cause abnormality on one or more standard laboratory test results.

Two etiologic groups comprise most of the hemolytic anemias: those due primarily to intra corpuscular RBC defects and those due primarily to extracorpuscular agents acting on the RBCs. This provides a rational basis for classification of the hemolytic anemias, as follows.

Due Primarily to Intracorpuscular Defects

1. Hemoglobin structure abnormalities (e.g., sickle cell and Hb C disease)
2. Hemoglobin synthesis abnormalities (e.g., thalassemia)
3. RBC enzyme deficiencies (e.g., glucose-6-phosphate dehydrogenase deficiency)
4. RBC membrane abnormalities (e.g., congenital spherocytosis)

Due Primarily to Extracorpuscular Defects

1. Isoimmune antibodies (e.g., ABO transfusion reactions)
2. Autoimmune antibodies (e.g., cold agglutinins)
3. Drug-induced (e.g., a-methyldopa–induced hemolytic anemia)
4. Traumatic (“microangiopathic”) (e.g., disseminated intravascular coagulation)
5. Abnormal interaction with activated complement (e.g., paroxysmal nocturnal hemoglobinuria)
6. Toxins (e.g., lead, bacterial toxins)
7. Parasites (e.g., malaria)
8. Hypersplenism