The impact of tissue factor pathway inhibitor on coagulation kinetics determined by thrombelastography.
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.
Audu
Paul
P
Department of Anesthesiology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Nielsen
Vance G
VG
Armstead
Valerie
V
Powell
Garry
G
Kim
Jerry
J
Kim
Larry
L
Mehta
Munira
M
D001777:Blood Coagulation / Q000187:drug effects*; D007692:Diatomaceous Earth / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005168:Factor VII Deficiency / Q000097:blood; D006801:Humans; D008074:Lipoproteins / Q000097:blood / Q000494:pharmacology*; D013916:Thrombelastography / Q000187:drug effects*; D013925:Thromboplastin / Q000494:pharmacology
D008074:Lipoproteins; C051928:lipoprotein-associated coagulation inhibitor; D007692:Diatomaceous Earth; D013925:Thromboplastin