The glycoprotein IIb/IIIa antagonist c7E3 inhibits platelet aggregation in the presence of heparin-associated antibodies

T. K. Liem, R. Teel, S. Shukla, D. Silver, W. C. Krupski, T. K. Liem, J. Fareed, G. P. Clagett

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Purpose: Heparin-associated antibodies (HAAb), in the presence of heparin, can cause platelet activation and aggregation. The purpose of this study was to assess whether a platelet glycoprotein (GP) IIb/IIIa receptor antagonist, c7E3, would inhibit platelet aggregation in the presence of HAAb. If aggregation is inhibited by c7E3, enzyme-linked immunosorbent assays (ELISA) would be done to determine whether c7E3 interfered with the binding of heparin and the HAAb. Methods: HAAb-positive plasmas from 21 patients (determined by platelet aggregation assays) were studied. Normal donor platelet-rich plasmas (PRP) were incubated (1 minute) with either saline solution or 3 μg/ml of c7E3. Platelet poor plasma from patients with HAAb and one of three sources of heparin (25 μl, 10 U/ml; porcine heparin, bovine heparin, and low molecular weight heparin [enoxaparin]) were added to the PRP mixture. Aggregation was determined using a platelet aggregometer by measuring time to aggregation, the slope of the aggregation curve, and the percent change in optical density. Results: Platelet aggregation occured in 100%, 100%, and 95% of the saline solution incubations exposed to porcine heparin, bovine heparin, and enoxaparin, respectively. Incubation with c7E3 caused 100% inhibition of platelet aggregation in plasma exposed to porcine heparin, bovine heparin, and enoxaparin. The optical density curves obtained from the ELISA, which were dependent on the binding of HAAb to heparin, were not significantly different when c7E3 was compared to buffer alone. Conclusions: The GP IIb/IIIa receptor antagonist, c7E3, inhibits HAAb- induced platelet aggregation via a mechanism that does not appear to interfere with the binding between heparin and HAAb. Clinical trials are warranted to assess whether GP IIb/IIIa antagonists may allow patients with Haab to safely receive heparin.

Original languageEnglish (US)
Pages (from-to)124-130
Number of pages7
JournalJournal of vascular surgery
Volume25
Issue number1
DOIs
StatePublished - 1997
Externally publishedYes

ASJC Scopus subject areas

  • Surgery
  • Cardiology and Cardiovascular Medicine

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