Activated factor XI and tissue factor in aortic stenosis: links with thrombin generation.

In our previous studies, we showed that a significant proportion of patients with various cardiovascular diseases have active tissue factor (TF) and factor (F)XIa in their plasma. The objective of the present study was to evaluate these two proteins in plasma from patients with aortic stenosis and establish their relationship with the severity of the disease. Fifty-four consecutive patients with aortic stenosis, including 38 (70.4%) severe aortic stenosis patients, were studied. Plasma FXIa and TF activity were determined in clotting assays by measuring the response to inhibitory monoclonal antibodies. TF activity was detectable in plasma from 14 of 54 patients (25.9%), including 13 of 38 with severe aortic stenosis (34.2%) and one of 16 (6.25%) with moderate aortic stenosis (P=0.052). FXIa activity was found in 12 (22.2%) patients, mostly in individuals with severe aortic stenosis (11 of 38, 28.9%, P=0.067). All 12 patients with circulating FXIa had active TF in their plasma as well. Severe aortic stenosis patients with detectable TF had higher maximal (111±20 vs. 97±16 mmHg, P=0.02) and mean (61±12 vs. 53±8 mmHg, P=0.02) transvalvular gradient, compared with those without such activity in plasma. In severe aortic stenosis patients with detectable active TF, prothrombin fragment 1.2, a thrombin generation marker, was higher than that in patients without TF (375±122 vs. 207±64 pM, P<0.001). Detectable FXIa and TF activity was observed for the first time in aortic stenosis patients, primarily in severe ones. This activity correlates with thrombin generation in those patients.