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Prepublished online as a Blood First Edition Paper on June 28, 2002; DOI 10.1182/blood-2002-02-0471. This Article Full Text (PDF) All Versions of this Article: 2002-02-0471v1 101/1/58    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Seiffert, D. Articles by Billheimer, J. T Search for Related Content PubMed PubMed Citation Articles by Seiffert, D. Articles by Billheimer, J. T Social Bookmarking                   What's this? Submitted February 13, 2002 Accepted June 13, 2002 Prospective testing for drug-dependent antibodies reduces the incidence of thrombocytopenia observed with the small molecule glycoprotein IIb/IIIa antagonist Roxifiban: implications for the etiology of thrombocytopenia Dietmar Seiffert*, Andrew M Stern, William Ebling, Richard J Rossi, Yu Chen Barrett, Richard Wynn, Gregory F Hollis, Bokang He, Cathy J Kieras, Donna L Pedicord, Debra A Cromley, Tsushung A Hua, Robert B Stein, Robert N Daly, Anthony Sferruza, Henry J Pieniaszek, and Jeffrey T Billheimer Chemical Enzymology, Bristol-Myers Squibb, Wilmington, DE, USA * Corresponding author; email: dietmar.seiffert{at}bms.com. Thrombocytopenia is a relatively common side effect observed during glycoprotein (GP) IIb/IIIa antagonist therapy. With the oral antagonist Roxifiban, we observed thrombocytopenia, defined as 50% reduction of platelets over pre-dose values or below 90,000 per microliter, with a frequency of 2 percent (8/386). Thrombocytopenia occured either early (days 2-4) or delayed (days 11-16). No additional cases were observed with up to 6 month of treatment. Retrospective analysis provided evidence for drug-dependent antibodies (DDABs) to GP IIb/IIIa in 5 out of 6 subjects, suggestive of an immune etiology of thrombocytopenia. The hypothesis that excluding patients based on positive DDAB reaction would reduce the frequency of thrombocytopenia was tested. Patients were screened for DDABs during the study qualification period, and overall, 3.9% of the patients were excluded based on pre-existing DDAB concentrations above a statistically defined medical decision limit. Additional 2.6% were excluded based on therapy-related antibody production during the first 2 weeks. With antibody testing, 0.2 percent (2/1044) patients developed immune-mediated thrombocytopenia. One case developed a rapidly increasing antibody concentration and presented with thrombocytopenia despite discontinuation of Roxifiban therapy. The second case was related to a false negative test result. The frequency of thrombocytopenia was statistically significantly reduced from 2% to 0.2% (p=0.0007) comparing non-screened and screened patients. Testing for DDABs can reduce the frequency of thrombocytopenia in patients treated with Roxifiban and by analogy other GP IIb/IIIa antagonists. Thus, DDAB testing may be employed to increase the safety of GP IIb/IIIa antagonists. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. H. Aster Immune Thrombocytopenia Caused by Glycoprotein IIb/IIIa Inhibitors Chest, February 1, 2005; 127(2_suppl): 53S - 59S. [Abstract] [Full Text] [PDF] M. Schwarz, Y. Katagiri, M. Kotani, N. Bassler, C. Loeffler, C. Bode, and K. Peter Reversibility versus Persistence of GPIIb/IIIa Blocker-Induced Conformational Change of GPIIb/IIIa ({alpha}IIb{beta}3, CD41/CD61) J. Pharmacol. Exp. Ther., March 1, 2004; 308(3): 1002 - 1011. [Abstract] [Full Text] [PDF]

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