Introduction

Hemolysis, the destruction of red blood cells, can be categorized based on the site of hemolysis (intravascular vs. extravascular), the relation to the red cell (intrinsic vs. extrinsic), or the pattern of onset (inherited vs. acquired) (Fig. 5.1). The severity of the clinical findings in hemolysis depends on many factors, which are discussed below (Table 5.1). It is important to determine the underlying cause of hemolysis since the medical management may be different.

Immune-mediated hemolytic anemias

Immune-mediated hemolytic anemias result from intravascular or extravascular hemolysis triggered by various intrinsic and extrinsic factors. While the intravascular hemolysis occurs predominantly in the blood vessels, the extravascular hemolysis, which accounts for most cases of hemolytic anemia, is due to elimination of red cells by phagocytes in the spleen, liver, and bone marrow. Activation of the classic complement cascade is the main pathogenetic mechanism leading to immune-mediated hemolysis. Certain classes of antibodies are more effective than others at activating complement (IgM > IgG3 > IgG1 > IgG2). More commonly, the red cell is coated with complement C3b and C3d, and, less frequently, the activation of the complement cascade leads to the formation of membrane attack complex and red cell lysis [1, 2]. Since the liver macrophages do not harbor a C3d receptor, the red cells are not prematurely destroyed. Different antibody classes mediate the hemolytic process differently.