Effects of tirofiban on haemostatic activation in vitro

Kenichi A. Tanaka, N. Katori, F. Szlam, N. Sato, A. B. Kelly, A. H. Levy

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Abstract

Background. Thrombin plays a critical role in normal haemostasis and pathological thrombosis. Heparin has long been a mainstay choice of antithrombotic regimen in cardiac patients, but persistent thrombin generation seems to occur during heparin therapy. Because platelets are integral to primary haemostasis and clot formation, we evaluated the use of tirofiban (Aggrastat®), a platelet inhibitor, as a therapy to improve heparin sensitivity and delay thrombin formation. Methods. Blood samples were obtained from healthy subjects (n=8) and cardiac surgical patients (n=34). Thrombin formation was measured in platelet-rich plasma with a Thrombogram®-Ascent fluorescent plate reader system. Platelet inhibition by tirofiban was evaluated with Plateletworks®, and the interaction of tirofiban and heparin (> 1.5 U ml-1) on clot formation was evaluated with Sonoclot Analyzer® or kaolin activated clotting times (ACTs). Results. Addition of tirofiban (70-280 ng ml-1) progressively delayed onset of thrombin generation triggered by adenosine diphosphate (ADP). Plateletworks showed platelet inhibition with tirofiban (>35 ng ml-1), whereas heparin per se failed to produce platelet inhibition at 7 U ml-1. Heparin (1.5 U ml-1) slowed the onset and rate of fibrin formation on Sonoclot analyses, and this was further slowed after addition of tirofiban (70 ng ml-1) to heparin-containing blood samples. Significant increases in ACT at all heparin concentrations were observed with the addition of tirofiban (70 ng ml-1). The addition of antithrombin (0.2 units/ml) to heparinized blood samples further prolonged ACTs, but the difference was not statistically significant when compared with heparin alone. Conclusion. Tirofiban delays platelet activation-mediated thrombin generation and prolongs ACT in heparinized blood.

Original languageEnglish
Pages (from-to)263-269
Number of pages7
JournalBritish Journal of Anaesthesia
Volume93
Issue number2
DOIs
Publication statusPublished - 2004 Aug
Externally publishedYes

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Keywords

  • Blood, antithrombin
  • Blood, platelet inhibitors, tirofiban
  • Complications, heparin

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Tanaka, K. A., Katori, N., Szlam, F., Sato, N., Kelly, A. B., & Levy, A. H. (2004). Effects of tirofiban on haemostatic activation in vitro. British Journal of Anaesthesia, 93(2), 263-269. https://doi.org/10.1093/bja/aeh193