Differences in free and total tissue factor pathway inhibitor, and tissue factor in peripheral artery disease compared to healthy controls

Tissue factor (TF) is one of the major initiators of coagulation and raised plasma levels have been found in various cardiovascular diseases. TF activity is, however, regulated by tissue factor pathway inhibitor (TFPI), and alteration in levels of TF and/or TFPI may thus relate to thrombogenesis and atherogenesis. To investigate possible abnormalities in TF and free TFPI (i.e. unbound to TF) and total TFPI among patients with peripheral artery disease (PAD), we studied 42 patients (mean age 57, 35 men) with objectively proven (by ABPI/Doppler) disease and 42 age- and sex- matched healthy controls. TF, free TFPI and total TFPI were measured in citrated plasma by ELISA. TF was higher in the patients with PAD compared to controls (275±122 pg/ml versus 158±60, P<0.0001) but levels of total TFPI were lower in the patients (43±10 ng/ml versus 50±15, P=0.021). There was no significant difference in levels of free TFPI between patients and controls (7.2±1.5 ng/ml in controls, 7.5±1.6 among patients, P=0.39). Within the control patients, levels of free and total TFPI were significantly correlated (Spearman r=0.51, P=0.001) but in the patients with PAD this correlation was poor (r=0.21, P=0.178). We suggest that reduced levels of total TFPI and raised levels of TF may contribute to the process of atherogenesis and the increased risk of thrombosis among patients with cardiovascular disease.