TY - JOUR
T1 - Two Mechanistic Pathways for Thienopyridine-Associated Thrombotic Thrombocytopenic Purpura. A Report From the SERF-TTP Research Group and the RADAR Project
AU - Bennett, Charles L.
AU - Kim, Benjamin
AU - Zakarija, Anaadriana
AU - Bandarenko, Nicholas
AU - Pandey, Dilip K.
AU - Buffie, Charlie G.
AU - McKoy, June M.
AU - Tevar, Amul D.
AU - Cursio, John F.
AU - Yarnold, Paul R.
AU - Kwaan, Hau C.
AU - De Masi, Davide
AU - Sarode, Ravindra
AU - Raife, Thomas J.
AU - Kiss, Joseph E.
AU - Raisch, Dennis W.
AU - Davidson, Charles
AU - Sadler, J. Evan
AU - Ortel, Thomas L.
AU - Zheng, X. Long
AU - Kato, Seiji
AU - Matsumoto, Masanori
AU - Uemura, Masahito
AU - Fujimura, Yoshihiro
PY - 2007/9/18
Y1 - 2007/9/18
N2 - Objectives: We sought to describe clinical and laboratory findings for a large cohort of patients with thienopyridine-associated thrombotic thrombocytopenic purpura (TTP). Background: The thienopyridine derivatives, ticlopidine and clopidogrel, are the 2 most common drugs associated with TTP in databases maintained by the U.S. Food and Drug Administration (FDA). Methods: Clinical reports of TTP associated with clopidogrel and ticlopidine were identified from medical records, published case reports, and FDA case reports (n = 128). Duration of thienopyridine exposure, clinical and laboratory findings, and survival were recorded. ADAMTS13 activity (n = 39) and inhibitor (n = 30) were measured for a subset of individuals. Results: Compared with clopidogrel-associated TTP cases (n = 35), ticlopidine-associated TTP cases (n = 93) were more likely to have received more than 2 weeks of drug (90% vs. 26%), to be severely thrombocytopenic (84% vs. 60%), and to have normal renal function (72% vs. 45%) (p < 0.01 for each). Compared with TTP patients with ADAMTS13 activity >15% (n = 13), TTP patients with severely deficient ADAMTS13 activity (n = 26) were more likely to have received ticlopidine (92.3% vs. 46.2%, p < 0.003). Among patients who developed TTP >2 weeks after thienopyridine, therapeutic plasma exchange (TPE) increased likelihood of survival (84% vs. 38%, p < 0.05). Among patients who developed TTP within 2 weeks of starting thienopyridines, survival was 77% with TPE and 78% without. Conclusions: Thrombotic thrombocytopenic purpura is a rare complication of thienopyridine treatment. This drug toxicity appears to occur by 2 different mechanistic pathways, characterized primarily by time of onset before versus after 2 weeks of thienopyridine administration. If TTP occurs after 2 weeks of ticlopidine or clopidogrel therapy, therapeutic plasma exchange must be promptly instituted to enhance likelihood of survival.
AB - Objectives: We sought to describe clinical and laboratory findings for a large cohort of patients with thienopyridine-associated thrombotic thrombocytopenic purpura (TTP). Background: The thienopyridine derivatives, ticlopidine and clopidogrel, are the 2 most common drugs associated with TTP in databases maintained by the U.S. Food and Drug Administration (FDA). Methods: Clinical reports of TTP associated with clopidogrel and ticlopidine were identified from medical records, published case reports, and FDA case reports (n = 128). Duration of thienopyridine exposure, clinical and laboratory findings, and survival were recorded. ADAMTS13 activity (n = 39) and inhibitor (n = 30) were measured for a subset of individuals. Results: Compared with clopidogrel-associated TTP cases (n = 35), ticlopidine-associated TTP cases (n = 93) were more likely to have received more than 2 weeks of drug (90% vs. 26%), to be severely thrombocytopenic (84% vs. 60%), and to have normal renal function (72% vs. 45%) (p < 0.01 for each). Compared with TTP patients with ADAMTS13 activity >15% (n = 13), TTP patients with severely deficient ADAMTS13 activity (n = 26) were more likely to have received ticlopidine (92.3% vs. 46.2%, p < 0.003). Among patients who developed TTP >2 weeks after thienopyridine, therapeutic plasma exchange (TPE) increased likelihood of survival (84% vs. 38%, p < 0.05). Among patients who developed TTP within 2 weeks of starting thienopyridines, survival was 77% with TPE and 78% without. Conclusions: Thrombotic thrombocytopenic purpura is a rare complication of thienopyridine treatment. This drug toxicity appears to occur by 2 different mechanistic pathways, characterized primarily by time of onset before versus after 2 weeks of thienopyridine administration. If TTP occurs after 2 weeks of ticlopidine or clopidogrel therapy, therapeutic plasma exchange must be promptly instituted to enhance likelihood of survival.
UR - http://www.scopus.com/inward/record.url?scp=34548542028&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34548542028&partnerID=8YFLogxK
U2 - 10.1016/j.jacc.2007.04.093
DO - 10.1016/j.jacc.2007.04.093
M3 - Article
C2 - 17868804
AN - SCOPUS:34548542028
SN - 0735-1097
VL - 50
SP - 1138
EP - 1143
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 12
ER -