Effects of SolCD39, a novel inhibitor of platelet aggregation, on platelet deposition and aggregation after PTCA in a porcine model

John M. Buergler, Charles R. Maliszewski, M. Johan Broekman, Grzegorz L. Kaluza, Daryl G. Schulz, Aaron J. Marcus, Albert E. Raizner, Neal S. Kleiman, Nadir M. Ali

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Introduction: This study evaluated CD39 in a porcine model of balloon angioplasty and in plasma of patients undergoing percutaneous intervention. CD39 (E-NTPDase1), is the endothelial ecto-ADPase inhibiting platelet function via hydrolysis of released platelet ADP. Methods and Results: A recombinant soluble form of CD39 (solCD39) given intravenously to pigs had an elimination half life of 5-7 days, increased the bleeding time to an extent similar to aspirin, and inhibits platelet aggregation by > 90%. Platelet counts and clot retraction remained normal following solCD39 administration. In a pig model of acute coronary balloon injury, solCD39 resulted in non-statistically significant decreases in platelet (7.7 ± 1.4 versus 11.7 plusmn; 3.4) and fibrin (3.5 ± 0.4 versus 4.2 ± 0.7) deposition ratios. Adding ex vivo to human platelet rich plasma (PRP) solCD39 produced nearly 100% inhibition of ADP-induced platelet aggregation. A dose-response effect of solCD39 on platelet aggregation induced by collagen or a thrombin receptor activating peptide (TRAPSFLLRN) was noted in PRP obtained from volunteers and patients receiving aspirin, clopidogrel or ticlopidine. SolCD39 also provided additional and complete inhibition of TRAP-induced platelet aggregation in PRP from patients who had received abciximab, aspirin and clopidogrel. Conclusions: SolCD39, a novel inhibitor of platelet activation and recruitment with a relatively long half-life appears to be well tolerated and is a potent inhibitor of ADP-, collagen-, or TRAP-induced platelet activation. Its potential use in percutaneous coronary intervention requires further study.

Original languageEnglish (US)
Pages (from-to)115-122
Number of pages8
JournalJournal of Thrombosis and Thrombolysis
Volume19
Issue number2
DOIs
StatePublished - Apr 2005

Keywords

  • ADP
  • Balloon angioplasty
  • Nucleotidases
  • Platelet activation
  • Platelets
  • Thrombosis

ASJC Scopus subject areas

  • Hematology
  • Cardiology and Cardiovascular Medicine

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