Blood, 1 January 2003, Vol. 101, No. 1, pp. 1-1
Thrombocytopenia induced by GPIIB/IIIA inhibitors
The GPIIb/IIIa antagonists are a new and promising class of
antithrombotic agents that bind specifically to GPIIb/IIIa
(
IIb
3 integrin), inhibit its interaction
with fibrinogen, and prevent platelet aggregation. Three GPIIb/IIIa
inhibitors
abciximab, tirofiban, and eptifibatideare approved in the
US and are widely used, mainly to reduce the incidence of secondary
complications following coronary angioplasty. In clinical trials, 0.5%
to 2% of patients treated with these agents experienced acute
thrombocytopenia, often severe. Recent reports indicate that this
complication is caused by antibodies that recognize GPIIb/IIIa
complexed to one of these drugs (Curtis et al, Blood.
2002;99:2054-2059; Bougie et al, Blood. 2002;100:2071-2076). Curiously,
such antibodies can be found in persons never exposed to one of these
drugs. Thus, thrombocytopenia can be triggered by the very first dose
of medication.
In this issue, Seiffert and colleagues (page 58) describe studies of
patients treated with the GPIIb/IIIa inhibitor roxifiban, which, in
contrast to currently approved drugs, can be given orally, making it
potentially suitable for long-term administration. In a preliminary
trial, about 2% of patients given roxifiban developed thrombocytopenia, some acutely and some after 1-2 weeks. Steps were
then taken to prescreen trial participants for antibodies before
treatment and periodically thereafter. About 6.5% developed antibodies
acutely or within 1 or 2 weeks of starting treatment and were withdrawn
from the trial. Of the remaining participants, only 0.2% had a
significant drop in platelet levels. Thus, prescreening for antibodies
reduced the incidence of this complication by about 90%. Because
thrombocytopenia can be particularly serious in a patient whose few
remaining platelets are dysfunctional, these findings are encouraging.
Further studies of this type should be considered if practical,
cost-effective methods for antibody detection can be devised.
Richard Aster
Blood Center of Southeast Wisconsin, Medical College of
Wisconsin
