Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome

Abstract

Thrombotic thrombocytopenic purpura (TTP) is an uncommon multisystemic disorder, sometimes associated with predisposing conditions such as pregnancy, cancer, exposure to certain drugs, bone marrow transplantation and HIV infection. In adults, the hemolytic uremic syndrome (HUS) and TTP are clinically and pathologically indistinguishable, except for the severity of renal failure. An abnormal interaction between the vascular endothelium and platelets in certain organs leads to thrombosis, endothelial proliferation, minimal inflammation and microangiopathic hemolysis. The endothelial cell disturbance and apoptosis caused by a plasma factor as yet unidentified, may lead to the release of unusually large von Willebrand factor (ULvWF) polymers, which facilitate the deposition of platelet microthrombi. The recent findings of complete deficiency of the vWF-cleaving metalloprotease in the chronic/relapsing form of TTP, which is often familial, the neutralization of the enzyme by a specific autoantibody that develops transiently and tends to disappear during remission in the more common acute form of TTP, and the normal levels of the metalloprotease and absence of inhibitory antibodies in HUS, have elucidated to a great extent the pathogenesis of TTP/HUS. Plasmapheresis remains the cornerstone of the management of TTP.