In vitro efficacy of platelet glycoprotein IIb/IIIa antagonist in blockingplatelet function in plasma of patients with heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is an important complication followi ng administration of heparin. Platelet activation and aggregation induced b y heparin/platelet factor 4/immunoglobulin complexes are thought to be the underlying mechanism for this condition, so it was hypothesized that abcixi mab (a humanized murine monoclonal antibody directed against the glycoprote in IIb/IIIa receptor) would prevent heparin-induced platelet aggregation an d activation in plasma from patients with HIT. Platelet aggregation was tes ted in vitro with platelet-poor plasma (obtained from 23 patients with HIT) , platelet-rich plasma (from normal donors with known reactivity), heparin (0.5 U/ml), and ascending doses of abciximab (0.07-0.56 mu g/ml). The abili ty of abciximab to prevent platelet activation was also evaluated using flo w cytometry (P selectin expression, mepacrine release, microparticle format ion) and platelet factor 4 immunoassay. In vitro, abciximab inhibited hepar in-induced platelet aggregation in a dose-dependent fashion (IC50 0.103 mu g/ml) and inhibited microparticle formation, the expression of P-selectin, release of mepacrine and platelet factor 4. These findings suggest that abc iximab may be useful in treatment of patients with HIT and warrants further clinical evaluation.