Differences between mechanisms of intravascular and extravascular immune hemolysis

A: Intravascular hemolysis occurs when complement is fixed and red blood cells lyse in the circulation, releasing free hemoglobin. Lysis occurs because the membrane attack complex (MAC) creates holes in the red blood cell membrane. Typically IgM is responsible for fixing complement (as shown) although other mechanisms may be involved.  
B: Extravascular hemolysis occurs when reticuloendothelial macrophages (mostly in the liver and spleen) phagocytize antibody (or complement component C3)-coated red blood cells. This can occur in stages, with production of spherocytes and microspherocytes that are trapped in splenic sinusoids, or all at once. Refer to UpToDate topics on immune hemolysis and hemolytic transfusion reactions for details.