Thrombosis complicating the rupture of an atherosclerotic plaque can lead to arterial occlusion. Tissue factor, a membrane-bound glycoprotein, is expressed to a greater extent in atherosclerotic plaques and may be a key mediator of microthrombosis and macrothrombosis. This pilot study was designed to determine whether the angiographic presence or the extent of atherosclerosis was correlated with the activity of coagulation factors in blood. A novel computational model was used to predict whether differences in the activity of coagulation factors would alter the generation of thrombin.Methods
Blood was obtained for the determination of coagulation factor activity from patients undergoing cardiac catheterization (n=50) who were grouped by the extent of their coronary artery disease (CAD). Generation of thrombin and factor (f) Xa were determined computationally.Results
The activities of fII and fX were significantly lower in blood from patients with more severe CAD. Despite this, the time to clot (presumably reflecting a hypercoagulable state) was shorter in all patient groups than projected in healthy participants. Tissue factor pathway inhibitor concentrations were strongly associated with the generation of fXa and thrombin, and it is the best predictor of the time to clot.Conclusion
The balance between tissue factor and tissue factor pathway inhibitor appears to be a primary determinant of a hypercoagulable state that can accompany CAD. Lower concentrations of fX and fII in blood from patients with more severe CAD, who exhibit a shorter time to clot in vitro, are consistent with the clinical observation that patients at greater risk for thrombosis can also be at greater risk for bleeding.