Von Willebrand Factor in Thrombotic Thrombocytopenic Purpura

Abstract

IntroductionThrombotic thrombocytopenic purpura (TTP), a disseminated form of thrombotic microangiopathy, was initially described by Moschcowitz in 1924.1 TTP is defined by a pentad of findings, including severe thrombocytopenia, intravascular hemolysis with erythrocyte fragmentation, neurologic deficit, renal dysfunction, and fever.2–4 The thrombocytopenia occurs in the presence of normal or even increased numbers of megakaryocytes in the bone marrow, suggesting increased consumption. Platelet aggregates, found in the microcirculation, contain little if any fibrin polymers, indicating that activation of coagulation and fibrin formation may be secondary and limited in extent.About one-third of patients experience recurrent acute episodes at irregular and unpredictable intervals, whereas the majority of patients who recover from an acute TTP event experience no relapse and no persistent organ failure. TTP is usually classified as relapsing if complete remissions occurred between acute events and as chronic if complete recovery did not occur between bouts.Genetic predisposition to TTP has been shown in several siblings suffering from recurrent TTP.5 Thus, cases of TTP can be further divided according to whether the disease has a familial or genetic component or is not heritable. Acute episodes of TTP may be triggered by viral or bacterial infection, autoimmune disorders, bone marrow transplantation, drug therapy, cancer, chemotherapy, and pregnancy.3,4 The incidence of TTP is estimated to be two to eight cases per million people per year.3,6 Until four decades ago, the mortality rate was virtually 100% but has since decreased to less than 20% after introduction of plasma therapy. Still, there were more than 4,500 TTP-associated deaths recorded in the United States between 1968 and 1991.6