Thrombotic thrombocytopenic purpura--a syndrome caused by multiple pathogenetic mechanisms

Platelet thrombus formation in small vessels in thrombotic thrombocytopenic purpura (TTP) is triggered by certain stimuli to cause vascular injury, primary platelet aggregation, or both. The formation and dissolution of platelet thrombi are modulated by proteolysis, plasma factors, PGI2 synthesis and stability, and immune mechanisms. It has been demonstrated that TTP plasmas contain heterogeneous platelet aggregating factors and that TTP plasmas induce the apoptosis of microvascular endothelial cell. Fibrinolysis has been shown decreased. Von Willebrand factor (vWF) under high shear stress is unfolded and becomes adhesive to platelets to induce platelet aggregation. Recently it is found that vWF protease is deficient in hereditary TTP, intermittent relapsing TTP, idiopathic acute TTP and ticlopidine- and clopidogrel-induced TTP, but normal in hemolytic uremic syndrome and organ transplantation-related thrombotic microangiopathy. Apparently absence of vWF protease leaves unfolded adhesive vWF unchecked to cause platelet aggregation. Antibodies against vWF protease are present in intermittent relapsing TTP, idiopathic acute TTP, and ticlopidine-induced TTP. Plasma exchange and/or infusion with or without corticosteroids remain the cornerstone of treatment.