Thrombin mutant W215A/E217A acts as a platelet GPIb antagonist

Michelle A. Berny, Tara C. White, Erik I. Tucker, Leslie A. Bush-Pelc, Enrico Di Cera, András Gruber, Owen J.T. McCarty

Research output: Contribution to journalArticlepeer-review

37 Scopus citations


OBJECTIVE - Thrombin containing the mutations Trp215Ala and Glu217Ala (WE) selectively activates protein C and has potent antithrombotic effects in primates. The aim of this study was to delineate the molecular mechanism of direct WE-platelet interactions under static and shear conditions. METHODS AND RESULTS - Purified platelets under static conditions bound and spread on immobilized wild-type but not WE thrombin. In PPACK-anticoagulated blood under shear flow conditions, platelets tethered and rolled on both wild-type and WE thrombin, and these interactions were abrogated by the presence of a glycoprotein Ib (GPIb)-blocking antibody. Platelet deposition on collagen was blocked in the presence of WE, but not wild-type thrombin or prothrombin. WE also abrogated platelet tethering and rolling on immobilized von Willebrand factor in whole blood under shear flow. CONCLUSIONS - These observations demonstrate that the thrombin mutant WE, while not activating platelets, retains the ability to interact with platelets through GPIb, and inhibits GPIb-dependent binding to von Willebrand factor-collagen under shear.

Original languageEnglish (US)
Pages (from-to)329-334
Number of pages6
JournalArteriosclerosis, thrombosis, and vascular biology
Issue number2
StatePublished - Feb 2008


  • GPIb
  • Platelet
  • Thrombin
  • Von Willebrand factor

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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