Pathophysiology of thrombotic thrombocytopenic purpura : the "two-hit" paradigm

Abstract

Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening disease characterized by acute episodes of widespread thrombosis in capillaries and small arteries. The discovery that the plasmatic activity of the von Willebrand factor cleaving protease, ADAMTS13, is severely deficient in patients with TTP represented a turning point in the understanding of the pathophysiology of the disease. In spite of recent advances, the clinical course of TTP is characterized by considerable heterogeneity, the causes of which are largely unknown. Herein, we present a number of studies investigating the determinants of clinical heterogeneity in patients with both congenital and acquired forms of TTP. A __two-hit__ model of the pathophysiology of TTP is presented