Thrombotic microangiopathy, hemolytic uremic syndrome, and thrombotic thrombocytopenic purpura

The term thrombotic microangiopathy (TMA) defines a lesion of vessel wall t hickening (mainly arterioles or capillaries), intraluminal platelet thrombo sis, and partial or complete obstruction of the vessel lumina. Depending on whether renal or brain lesions prevail, two pathologically indistinguishab le but somehow clinically different entities have been described: the hemol ytic uremic syndrome (HUS) and the thrombotic thrombocytopenic purpura (TTP ). Injury to the endothelial cell is the central and likely inciting factor in the sequence of events leading to TMA. Loss of physiological thrombores istance, leukocyte adhesion to damaged endothelium, complement consumption, abnormal von Willebrand factor release and fragmentation, and increased va scular shear stress may then sustain and amplify the microangiopathic proce ss. Intrinsic abnormalities of the complement system and of the von Willebr and factor pathway may account for a genetic predisposition to the disease that may play a paramount role in particular in familial and recurrent form s. Outcome is usually good in childhood, Shiga toxin-associated HUS, wherea s renal and neurological sequelae are more frequently reported in adult, at ypical, and familial forms of HUS and in TTP. Plasma infusion or exchange i s the only treatment of proven efficacy. Bilateral nephrectomy and splenect omy may serve as rescue therapies in very selected cases of plasma resistan t HUS or recurrent TTP, respectively.