Coagulation in the pathophysiology of hemolytic anemias

Coagulation abnormalities are frequently reported in hemolytic anemias (HA). Several pathophysiologic mechanisms are common to different HA. In this review three different hemolytic disorders will be discussed. In sickle cell disease and in beta-thalassemia, a thrombophilic status has been well documented as multifactorial involving hemostatic changes and activation of the coagulation cascade. Moreover, in such disorders, elevated levels of endothelial adhesion protein (ICAM-1, ELAM-1, VCAM-1, von Willebrand factor, and thrombomodulin) are often increased, suggesting that endothelial activation may be involved in vascular occlusion. As an additional mechanism of hypercoagulability in thalassemia, a procoagulant status of thalassemic red cells was recognized. The main clinical manifestation of paroxysmal nocturnal hemoglobinuria (PNH) is HA, and the most common complications are thrombosis, pancytopenia, and myelodysplastic syndrome or acute leukemia. The intravascular hemolysis is explained by a deficiency of glycosil phosphatidylinositol (GPI)-anchored complement regulatory proteins such as CD59 and CD55 on the membrane of red blood cells (RBCs), but the mechanism responsible for the increased incidence of thrombotic events in PNH remains unclear. Recent advances have been made in understanding the coagulation involvement in a heterogeneous group of diseases, thrombotic microangiopathies (TMA) characterized by microangiopathic hemolytic anemia and thrombocytopenia due to platelet clumping in the microcirculation, leading to ischemic organ dysfunction with neurologic symptoms and renal impairment.