In Vitro Efficacy of Platelet Glycoprotein IIb/IIIa Antagonist in Blocking Platelet Function in Plasma of Patients with Heparin-induced Thrombocytopenia

Abstract

SummaryHeparin-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 μg/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 μg/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.

Múltiplos Episódios De Infarto Agudo Do Miocárdio Após Uso De Anticoagulante - Relato De Caso

“…HIT type II occurs in approximately 1% to 3% of patients exposed to heparin 8 . It is a immune disorder which leads to an increased risk of 20 to 40 times of arterial and venous tromboses 9 .…”

“…This score is composed by thrombocytopenia, time, thrombosis and other causes for thrombocytopenia (table 1) 1 . Scoring can lead to three estimate probability: low (score of 0-3), intermediate (score of 4-5) and high risk (score of [6][7][8]. (1) To confirm diagnosis, laboratory testing may be performed: washed platelet activation assays and commercial PF4/polyanion enzyme immunoassays (EIAs), both sensitive for detecting clinically relevant HIT antibodies.…”

Coronary Artery Stent Thrombosis Associated with Heparin‐Induced Thrombocytopenia: Case Report and Review of the Literature

“…Activated platelets initiate thrombin generation in a cascade of events that leads to devastating thromboembolic complications. The platelet inhibitory effects of Glycoprotein IIb/IIIa receptor blockers (GRB) are well‐established, and these agents have been shown to reduce the in vitro heparin‐induced platelet aggregation observed in the plasma of patients with HIT 24 . Although direct thrombin inhibition is not specifically indicated for combined use with a GRB, the combination of argatroban and GRB has been evaluated in 152 patients (non‐HIT) undergoing elective percutaneous coronary intervention.…”

Heparin-induced thrombocytopenia: natural history, diagnosis, and management

“…In vitro, glycoprotein IIb/IIIa antagonists inhibit HIT-IgG-induced platelet aggregation, but in vivo data are limited. 60,61 Walenga et al reported the successful use of a direct thrombin inhibitor combined with tirofiban or abciximab in three patients with HIT. 62 Surgical thromboembolectomy and pharmacological thrombolysis should be reserved for selected patients.…”