All individuals have circulating antibodies directed against red blood cells, but their concentrations are often too low to trigger<unk>  (titers under 64 at 4 °C). In individuals with<unk> , these antibodies are in much higher concentrations (titers over 1000 at 4 °C). At body temperatures of 28–31 °C, such as those encountered during winter months, and occasionally at body temperatures of 37 °C, antibodies (generally IgM) bind to the polysaccharide region of glycoproteins on the surface of red blood cells (typically the I antigen or Pr antigen). Binding of antibodies to red blood cells activates the classical pathway of the complement system. If the complement response is sufficient, red blood cells are damaged by the membrane attack complex, an effector of the complement cascade. In the formation of the membrane attack complex, several complement proteins are inserted into the red blood cell membrane, forming pores that lead to membrane instability and intravascular hemolysis (destruction of the red blood cell within the blood vessels). If the complement response is insufficient to form membrane attack complexes, then extravascular lysis will be favored over intravascular red blood cell lysis. In lieu of the membrane attack complex, complement proteins (particularly C3b and C4b) are deposited on red blood cells. This opsonization enhances the clearance of red blood cell by phagocytes in the liver, spleen, and lungs, a process termed extravascular hemolysis. Individuals with<unk>  present with signs and symptoms of hemolytic anemia. Those with secondary<unk><unk>  may also present with an underlying<unk> , often autoimmune.
Cold agglutinin disease
Atypical hemolytic uremic syndrome
MERRF syndrome
Serum sickness
Cold autoimmune hemolytic anemia
Michels Caskey syndrome
Hennekam syndrome
Uddanam nephropathy