The impact of tissue factor pathway inhibitor on coagulation kinetics determined by thrombelastography

Paul Audu, Vance G. Nielsen, Valerie Armstead, Garry Powell, Jerry Kim, Larry Kim, Munira Mehta

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

BACKGROUND: Tissue factor pathway inhibitor (TFPI) is a 40-kDa, endogenous protein that inhibits tissue factor (TF)-initiated coagulation by bonding with activated factor X (FXa). The TFPI/FXa complex then subsequently binds with TF/activated factor VII (FVIIa) complex, ultimately inhibiting thrombin generation. Heparin administration causes endothelial release of TFPI concentrations up to sixfold normal values. Thrombelastography (TEG®) is often used to monitor hemostasis in the perioperative period, and TFPI could potentially affect the diagnostic interpretation of TEG-based data, given its inhibition of both common and TF coagulation pathways. Thus, in this study we characterized the effect of TFPI on coagulation kinetics via TEG. METHODS: Whole blood, Factor VII-deficient plasma, and normal plasma were exposed in vitro to various concentrations of TFPI, after which unmodified, celite-activated, and TF-activated TEG were performed. RESULTS: The addition of 87.5 ng/mL TFPI (twice normal concentration) was required to prolong clot propagation in whole blood, with propagation and strength only significantly affected by the addition of 175 ng/mL concentrations. Experiments with Factor VII-deficient plasma demonstrated that TFPI-mediated suppression of coagulation kinetics at these concentrations was secondary to FXa inhibition. Celite activation markedly attenuated TFPI-mediated effects on coagulation kinetics, whereas TF activation accentuated TFPI-mediated prolongation of clot initiation and diminution of propagation. CONCLUSIONS: In settings involving heparin administration (e.g., cardiopulmonary bypass), TFPI-mediated inhibition of coagulation should be considered during TEG-based hemostatic monitoring.

Original languageEnglish (US)
Pages (from-to)841-845
Number of pages5
JournalAnesthesia and analgesia
Volume103
Issue number4
DOIs
StatePublished - Oct 1 2006
Externally publishedYes

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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