Thrombocytopenia Resulting from Sensitivity to GPIIb-IIIa Inhibitors

Abstract

Agents that inhibit the binding of fibrinogen to its platelet receptor (glycoprotein [GP] IIb-IIIa, alpha(IIb)/beta3 integrin) constitute a promising new group of antithrombotic drugs. Acute thrombocytopenia, often occurring within a few hours of starting treatment, is a recognized side effect of this family of compounds. Although most affected patients recover uneventfully, severe bleeding and fatal outcomes have been described. Both nonimmune and immune mechanisms have been implicated in the pathogenesis of this complication, but accumulating evidence suggests that drug-dependent antibodies are responsible for platelet destruction in many (and perhaps most) affected individuals. These antibodies are unique in that they can be present in persons not previously exposed to a GPIIb-IIIa inhibitor, allowing for the possibility that thrombocytopenia can occur within hours of starting treatment. Additional studies are needed to more fully define the characteristics of these antibodies and to identify risk factors that predispose patients to this complication.

Drug-Induced Hematologic Syndromes

“…In addition to inducing the desired platelet dysfunction, however, they can induce a severe thrombocytopenia in a small percentage of patients, likely through a drug- dependent antibody-mediated mechanism [40]. This may begin within hours to days and typically resolves spontaneously in 2–5 days.…”

Thrombocytopenia associated with the use of GPIIb/IIIa inhibitors: position paper of the ISTH working group on thrombocytopenia and GPIIb/IIIa inhibitors

“…In most reported cases, thrombocytopenia was severe (platelets <10 000 μ L −1 ) but bleeding symptoms were variable, ranging from none to a few petechiae to fatal intracranial hemorrhage. Upon discontinuation of treatment, platelet levels returned to normal in 2–5 days [1,2].…”

“…GPIIb/IIIa inhibitors are known to reduce the incidence of adverse complications after coronary angioplasty by inhibiting the reaction of fibrinogen with the activated platelets, and are now widely used. Acute thrombocytopenia is a recognized side effect of the three clinically approved inhibitors – tirofiban and eptifibatide, synthetic compounds that mimic or contain the Ang‐Gly‐Asp (RGD) peptide and bind tightly to the RGD recognition site in GPIIb/IIIa, and abciximab, a chimeric Fab fragment specific for an epitope on GPIIIa [1,2]. Although most patients experiencing thrombocytopenia after treatment with these drugs recover uneventfully, severe bleeding and fatalities have been described.…”

Human Platelet Antigens

“…156 Thrombocytopenia has been observed within hours of the initiation of treatment with such inhibitors and has become a recognized side effect of this drug therapy. Accumulated evidence argues that drug-dependent antibodies may be responsible for platelet destruction in a substantial portion of the affected recipients.…”