title: Impact of severe ADAMTS13 deficiency on clinical presentation and outcomes in patients with thrombotic microangiopathies: the experience of the Harvard TMA Research Collaborative.
abstract: 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 (TTP). 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 TTP, 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.
authors: Division of Hematology, Massachusetts General Hospital, Boston, MA, USA.|Harvard Medical School, Boston, MA, USA.
authors: Pavan K
authors: PK
authors: Bendapudi
authors: Harvard Medical School, Boston, MA, USA.|Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
authors: Ang
authors: A
authors: Li
authors: Harvard Medical School, Boston, MA, USA.|Division of Hematology and Oncology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
authors: Ayad
authors: A
authors: Hamdan
authors: Harvard Medical School, Boston, MA, USA.|Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
authors: Lynne
authors: L
authors: Uhl
authors: Harvard Medical School, Boston, MA, USA.|Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
authors: Richard
authors: R
authors: Kaufman
authors: Harvard Medical School, Boston, MA, USA.|Blood Transfusion Service, Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.
authors: Christopher
authors: C
authors: Stowell
authors: Harvard Medical School, Boston, MA, USA.|Blood Transfusion Service, Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.
authors: Walter
authors: W
authors: Dzik
authors: Harvard Medical School, Boston, MA, USA.|Blood Transfusion Service, Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.
authors: Robert S
authors: RS
authors: Makar
mesh_terms: D051722:ADAM Proteins / Q000172:deficiency*; D000071120:ADAMTS13 Protein; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D010951:Plasma Exchange / Q000379:methods*; D011697:Purpura, Thrombotic Thrombocytopenic / Q000175:diagnosis / Q000401:mortality / Q000628:therapy; D057049:Thrombotic Microangiopathies / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human
keywords: ADAMTS13; autoimmune thrombotic thrombocytopenic purpura; plasma exchange; thrombotic microangiopathy