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.

Luca Andrea Lotta was born in Milan (Italy) on May 16th 1983. In 2008, he graduated summa cum laude in Medicine and Surgery from the University of Milan. In 2009, after obtaining the Medical Licence from the Board of Medical Doctors of Milan he started his PhD studies on the pathophysiology of thrombotic thrombocytopenic purpura and on the genetic predisposition to common thrombotic diseases. He is currently a medical scientist at the Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan.