Evidence that thrombocytopenia observed in humans treated with orally bioavailable glycoprotein IIb/IIIa antagonists is immune mediated

Abstract

Glycoprotein (GP)IIb

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

“…Both patients underwent conversion to a highly positive drug-dependent antibody status temporally associated with thrombocytopenia. 13 Previous studies are consistent with the hypothesis that the antibodies bind to platelets in a roxifibandependent manner via their ability to recognize roxifiban-induced conformational changes in GP IIb/IIIa. 13 Here, we report that thrombocytopenia is a relatively common side effect during treatment with roxifiban and occurs with a frequency of about 2%.…”

“…The retrospective testing for DDABs in study DMP 754-010, parts A and B has been reported. 13 Thrombocytopenia is defined as reduction of the platelet number to below 90 000/L (9 ϫ 10 10 /L) or below 50% compared with predose values. In general, clinical samples were obtained at least 12 hours after the last treatment with roxifiban.…”

“…12 We recently reported 2 patients with drug-induced thrombocytopenia associated with roxifiban treatment. 13 The sample size was too small to obtain accurate estimates as to the frequency of thrombocytopenia or to generalize as to the prevailing pathomechanism in the patient population treated with roxifiban.…”

Antibodies causing thrombocytopenia in patients treated with RGD-mimetic platelet inhibitors recognize ligand-specific conformers of αIIb/β3 integrin

“…Between 0.1% and 2.0% of patients treated with tirofiban, eptifibatide, and other drugs of this class evaluated in clinical trials experienced acute thrombocytopenia, often severe, within a few hours of starting treatment, 5 a complication now known to be caused by Abs that recognize ␣ IIb /␤ 3 in a complex with the ligand mimetic drug being administered. [6][7][8][9][10] A unique feature of such Abs is that they can occur naturally in persons never previously exposed to one of these drugs, enabling thrombocytopenia to develop within a few hours of starting treatment. 7,11 Various mechanisms have been identified by which druginduced Abs cause thrombocytopenia.…”

A case of profound and prolonged tirofiban‐induced thrombocytopenia and its correction by intravenous immunoglobulin G

“…It has also been reported that Hcy can alter platelet function. Homocysteine has been found to stimulate platelet activation in vitro [2], enhance collagen type I-induced platelet aggregation [3], and increase platelet response to thrombin, combined with inhibition of the anti-aggregating NO formation [4], and induce oxidative stress, accompanied by increased arachidonic acid release [5]. Recently, Holven et al [6] reported that platelets from subjects with tHcy >20 lmol L )1 are characterized by increased collagen-induced translocation of CD62P to the platelet surface, along with higher plasma P-selectin levels compared with controls.…”