SEARCH:   Advanced

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Billheimer, J. T. Articles by Seiffert, D. Search for Related Content PubMed PubMed Citation Articles by Billheimer, J. T. Articles by Seiffert, D. Related Collections Hemostasis, Thrombosis, and Vascular Biology Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 May 2002, Vol. 99, No. 10, pp. 3540-3546 CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS Evidence that thrombocytopenia observed in humans treated with orally bioavailable glycoprotein IIb/IIIa antagonists is immune mediated Jeffrey T. Billheimer, Ira B. Dicker, Richard Wynn, Jodi D. Bradley, Debra A. Cromley, Helen E. Godonis, Lisa C. Grimminger, Bokang He, Cathy J. Kieras, Donna L. Pedicord, Susan M. Spitz, Beth E. Thomas, Nina I. Zolotarjova, Mary A. Gorko, Gregory F. Hollis, Robert N. Daly, Andrew M. Stern, and Dietmar Seiffert Glycoprotein (GP) IIb/IIIa antagonists are effective therapeutic agents, but elicit thrombocytopenia with a frequency that approaches 2%. Here, we provide evidence that thrombocytopenia in humans treated with the GP IIb/IIIa antagonist roxifiban is immune mediated. Two patients underwent conversion to a highly positive drug-dependent antibody (DDAB) status temporally associated with thrombocytopenia. Despite the continued presence of DDABs, the fall in platelet count was reversed by discontinuation of drug treatment, pointing to the exquisite drug dependency of the immune response. DDABs appear to bind to neoepitopes in GP IIb/IIIa elicited on antagonist binding. This information was used to develop an enzyme-linked immunosorbent assay (ELISA) for DDAB using solid-phase GP IIb/IIIa. A high level of specificity is indicated by the observation that DDAB binding is dependent on the chemical structure of the GP IIb/IIIa antagonist and that only 2% to 5% of human blood donors and 5% of chimpanzees present with pre-existing DDABs. Furthermore, none of 108 nonthrombocytopenic patients from the phase II roxifiban study showed an increase in antibody titer. Absorption of thrombocytopenia plasma with platelets reduced the DDAB ELISA signal, indicating that the test detects physiologically relevant antibodies. Screening patients for pre-existing or increasing DDAB titer during treatment with GP IIb/IIIa antagonists may reduce the incidence of drug-induced thrombocytopenia. © 2002 by The American Society of Hematology.   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] D. Seiffert, A. M. Stern, W. Ebling, R. J. Rossi, Y. C. Barrett, R. Wynn, G. F. Hollis, B. He, C. J. Kieras, D. L. Pedicord, et al. 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 Blood, January 1, 2003; 101(1): 58 - 63. [Abstract] [Full Text] [PDF]

	Copyright © 2002 by American Society of Hematology         Online ISSN: 1528-0020