In vitro efficacy of platelet glycoprotein IIb/IIIa antagonist in blocking platelet function in plasma of patients with heparin-induced thrombocytopenia.
Heparin-induced thrombocytopenia (HIT) is an important complication following administration of heparin. Platelet activation and aggregation induced by heparin/platelet factor 4/immunoglobulin complexes are thought to be the underlying mechanism for this condition, so it was hypothesized that abciximab (a humanized murine monoclonal antibody directed against the glycoprotein IIb/IIIa receptor) would prevent heparin-induced platelet aggregation and activation in plasma from patients with HIT. Platelet aggregation was tested 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 microg/ml). The ability of abciximab to prevent platelet activation was also evaluated using flow cytometry (P selectin expression, mepacrine release, microparticle formation) and platelet factor 4 immunoassay. In vitro, abciximab inhibited heparin-induced platelet aggregation in a dose-dependent fashion (IC50 0.103 microg/ml) and inhibited microparticle formation, the expression of P-selectin, release of mepacrine and platelet factor 4. These findings suggest that abciximab may be useful in treatment of patients with HIT and warrants further clinical evaluation.
Mak
K H
KH
Department of Cardiology and Joseph J. Jacobs Center for Vascular Biology, The Cleveland Clinic Foundation, OH 44195, USA.
Kottke-Marchant
K
K
Brooks
L M
LM
Topol
E J
EJ
D000077284:Abciximab; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D004353:Drug Evaluation, Preclinical; D005434:Flow Cytometry; D006493:Heparin / Q000009:adverse effects*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology*; D019007:P-Selectin / Q000032:analysis; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010978:Platelet Factor 4 / Q000378:metabolism; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors / Q000276:immunology*; D011796:Quinacrine / Q000032:analysis; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000276:immunology
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D010978:Platelet Factor 4; D006493:Heparin; D011796:Quinacrine; D000077284:Abciximab