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Blood, 15 September 2002, Vol. 100, No. 6, pp. 2071-2076
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Acute thrombocytopenia after treatment with tirofiban or
eptifibatide is associated with antibodies specific for
ligand-occupied GPIIb/IIIa
Daniel W. Bougie,
Peter R. Wilker,
Elizabeth D. Wuitschick,
Brian R. Curtis,
Mohammad Malik,
Stewart Levine,
Richard N. Lind,
Jaime Pereira, and
Richard H. Aster
From the Blood Research Institute, The Blood
Center of Southeastern Wisconsin, and the Departments of Medicine and
Pathology, Medical College of Wisconsin, St Luke's Medical Center,
Milwaukee; Veterans Administration Hospital, Asheville, NC; and
Catholic University of Chile, Santiago.
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 × 109/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.
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