Thrombosis in heritable hemolytic disorders.

Thromboses are a serious complication in patients with sickle cell disease, paroxysmal nocturnal hemoglobinuria, beta-thalassemia major, or thalassemia intermedia. Despite prophylaxis, thrombotic events can continue and can result in severe physical or mental debilitation or death of the patient. The fact that thrombosis does not occur in all patients with hemolytic anemias suggests that multiple factors interact to cause the coagulation crisis. Genetic modifiers, associated diseases, nutritional status, infections, environment, and treatment modalities are variables implicated in thrombophilia. The complexity confounds attempts to identify single causative agents in humans with hemolytic anemias. In the past year, mutations in putative genetic modifiers of the coagulation response have been examined as risk factors in patients with a history of thromboses; red cell binding sites on endothelial cells have been identified; and mouse models of thrombogenesis that permit experimental manipulation of single factors on a defined genetic background have been described.