Immune and Nonimmune Hemolytic Anemia

In humans, red blood cells (RBCs) make up a quarter of all cells in the body. Around two billion new RBCs are produced daily. Each RBC survives for about 120 days in the circulation (Shemin and Rittenberg, J Biol Chem. 166:627–636, 1946). Hemolysis is therefore defined as reduced survival of circulating RBCs due to premature destruction. Under steady state conditions, the rate of RBC production equals the rate of RBC loss. As a compensatory mechanism for hemolysis, increased erythropoiesis occurs in the bone marrow, with resultant increase in the reticulocyte count. Hemolytic anemia manifests when this compensatory mechanism cannot keep up with the increased destruction of erythrocytes. Hemolysis can result from intrinsic red cell abnormalities, extrinsic factors, or both. This chapter will discuss extrinsic or extracorpuscular causes of hemolytic anemia, which includes both immune and nonimmune-mediated mechanisms. RBC disorders secondary to intrinsic membrane protein defects, enzyme dysfunction, or hemoglobinopathy are covered in separate chapters. This chapter consists of the pathophysiology, clinical manifestations, and diagnosis and, finally, discusses treatment options for extrinsic causes of hemolytic anemia.