Impact of severe ADAMTS13 deficiency on clinical presentation and outcomes in patients with thrombotic microangiopathies: the experience of the Harvard TMA Research Collaborative

The Harvard TMA Research Collaborative is a multi-institutional registry-based effort to study thrombotic microangiopathies (TMA). Laboratory and clinical parameters were recorded for 254 cases of suspected autoimmune thrombotic thrombocytopenic purpura (TIP). Patients with severe ADAMTS13 deficiency (activity <= 10%, N = 68) were more likely to be young, female and without a history of cancer treatment or transplantation. While all patients with severe deficiency were diagnosed with autoimmune TIP, those without severe deficiency frequently had disseminated intravascular coagulation, drug-associated TMA and transplant-related TMA. Patients with severe ADAMTS13 deficiency had superior overall survival at 360 d compared to those without severe deficiency (93.0% vs. 47.5%, P < 0.0001). Almost all patients with severe deficiency received therapeutic plasma exchange (TPE), but the use of TPE in patients with ADAMTS13 activity >10% varied significantly across the institutions in our consortium (13.2-63.8%, P < 0-0001). Nevertheless, 90-d mortality was not different in patients with ADAMTS13 activity >10% between the three hospitals (P = 0-98). Our data show that patients with severe ADAMTS13 deficiency represent a clinically distinct cohort that responds well to TPE. In contrast, TMA. without severe ADAMTS13 deficiency is associated with increased mortality that may not be influenced by TPE.