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 (α_IIbβ₃ integrin), inhibit its interaction with fibrinogen, and prevent platelet aggregation. Three GPIIb/IIIa inhibitors—abciximab, tirofiban, and eptifibatide—are 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 About 6.5% developed antibodies acutely or within 1 or 2 weeks of starting treatment and were withdrawn from the trial.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.