The thrombin mutant W215A/E217A shows safe and potent anticoagulant and antithrombotic effects in vivo

Andras Gruber, Angelene M. Cantwell, Enrico Di Cera, Stephen R. Hansonr

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

Administration of the thrombin mutant W215A/E217A (WE), rationally designed for selective activation of the anticoagulant protein C, elicits safe and potent anticoagulant and antithrombotic effects in a baboon model of platelet-dependent thrombosis. The lowest dose of WE tested (0.011 mg/kg bolus) reduced platelet thrombus accumulation by 80% and was at least as effective as the direct administration of 40-fold more (0.45 mg/kg bolus) activated protein C. WE-treated animals showed no detectable hemorrhage or organ failure. No procoagulant activity could be detected for up to 1 week in baboon plasma obtained following WE administration. These results show that engineered thrombin derivatives that selectively activate protein C may represent useful therapeutic agents for the treatment of thrombotic disorders.

Original languageEnglish (US)
Pages (from-to)27581-27584
Number of pages4
JournalJournal of Biological Chemistry
Volume277
Issue number31
DOIs
StatePublished - Aug 2 2002

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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