Prospective testing for drug-dependent antibodies reduces the incidence of thrombocytopenia observed with the small molecule glycoprotein IIb/IIIa antagonist roxifiban: implications for the etiology of thrombocytopenia

Drug-induced thrombocytopenia and thrombosis: Evidence from patients receiving an oral glycoprotein IIb/IIIa inhibitor in the Orbofiban in Patients with Unstable coronary Syndromes- (OPUS-TIMI 16) trial

“…In the presence of certain GP IIb/IIIa inhibitors, however, drug dependent antibodies may enhance the destruction of platelets. For example, in patients who developed thrombocytopenia on a GP IIb/IIIa inhibitor, drug dependent antibodies to GP IIb/IIIa receptors were found in eight of ten patients taking xemilofiban [16] five of six patients treated with the oral agent roxifiban [17], and in 9 patients treated with eptifibatide and tirofiban [18].…”

Reversibility versus Persistence of GPIIb/IIIa Blocker-Induced Conformational Change of GPIIb/IIIa (αIIbβ3, CD41/CD61)

“…The existence of preformed anti-LIBS antibodies in patients, their binding to GPIIb/IIIa, and the resulting platelet sequestration has been considered to be a potential mechanism for GPIIb/IIIa blocker-induced thrombocytopenia (Madan and Berkowitz, 1999;Bougie et al, 2002;Seiffert et al, 2003). An incomplete disappearance of the LIBS epitopes after dissociation of the blocker might result in the prolonged sequestration of platelets that have been in contact with the GPIIb/IIIa blocker.…”

Thrombocytopenia Resulting from Sensitivity to GPIIb-IIIa Inhibitors

“…5 Roxifiban, an oral inhibitor, binds more tightly to GPIIb-IIIa than tirofiban and eptifibatide, and can be detected on platelets 1 week after the drug is discontinued. 46…”

“…61 In trials of another oral drug, roxifiban, the incidence of probable drug-induced thrombocytopenia was about 2%. 46 In both studies Figure 3 Reactions of immunoglobulin G (IgG) antibodies from patients who experienced thrombocytopenia after second exposure to abciximab (left) and antibodies found in normal persons (right) against platelets coated with the murine IgG1 monoclonal antibodies 7E3 and AP3. 7E3 contains peptide sequences that were incorporated into the chimeric abciximab molecule to endow it with specificity for the glycoprotein GPIIb-IIIa complex.…”

“…52 Platelet transfusions are indicated, however, in patients with significant bleeding symptoms. Some patients given the oral inhibitor xemilofiban, orbofiban, or roxifiban remained thrombocytopenic for as long as a week, 46,61 apparently because each of these agents persists longer in the circulation than tirofiban or eptifibatide.…”