Faculty Collaboration Database

Acute thrombocytopenia after treatment with tirofiban or eptifibatide is associated with antibodies specific for ligand-occupied GPIIb/IIIa. Blood 2002 Sep 15;100(6):2071-6

Date

08/30/2002

Pubmed ID

12200368

Scopus ID

2-s2.0-0037105428 (requires institutional sign-in at Scopus site)   190 Citations

Abstract

Acute thrombocytopenia is a recognized complication of treatment with GPIIb/IIIa inhibitors whose cause is not yet known. We studied 9 patients who developed severe thrombocytopenia (platelets less than 25 x 10(9)/L) within several hours of treatment with the GPIIb/IIIa inhibitors tirofiban (4 patients) and eptifibatide (5 patients). In each patient, acute-phase serum contained a high titer (range, 1:80-1:20 000) IgG antibody that reacted with the glycoprotein IIb/IIIa complex only in the presence of the drug used in treatment. Four patients had been previously treated with the same drug, but 5 had no known prior exposure. Pretreatment serum samples from 2 of the latter patients contained drug-dependent antibodies similar to those identified after treatment. No tirofiban- or eptifibatide-dependent antibodies were found in any of 100 randomly selected healthy blood donors, and only 2 of 23 patients receiving tirofiban or eptifibatide who did not experience significant thrombocytopenia had extremely weak (titer, 1:2) tirofiban-dependent antibodies. In preliminary studies, evidence was obtained that the 9 antibodies recognize multiple target epitopes on GPIIb/IIIa complexed with the inhibitor to which the patient was sensitive, indicating that they cannot all be specific for the drug-binding site. The findings indicate that acute thrombocytopenia after the administration of tirofiban or eptifibatide can be caused by drug-dependent antibodies that are "naturally occurring" or are induced by prior exposure to drug. These antibodies may be human analogs of mouse monoclonal antibodies that recognize ligand-induced binding sites (LIBS) induced in the GPIIb/IIIa heterodimer when it reacts with a ligand-mimetic drug.

Author List

Bougie DW, Wilker PR, Wuitschick ED, Curtis BR, Malik M, Levine S, Lind RN, Pereira J, Aster RH

Author

Brian Curtis PhD Director in the Platelet & Neutrophil Immunology Laboratory department at BloodCenter of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acute Disease
Aged
Autoantibodies
Calcium
Case-Control Studies
Cross Reactions
Epitopes
Female
Humans
Ligands
Male
Middle Aged
Peptides
Platelet Aggregation Inhibitors
Platelet Glycoprotein GPIIb-IIIa Complex
Thrombocytopenia
Tyrosine