Evaluation of factor XIa-alpha 1-antitrypsin in plasma, a contact phase-activated coagulation factor-inhibitor complex, in patients with coronary artery disease

Excess activated factor XI (FXIa) in plasma indicates increased activation during the contact phase of blood coagulation. To investigate the relationship between such elevations and coronary atherosclerosis, we examined FXIa values in patients with coronary artery disease (CAD) by an enzyme-linked immunosorbent assay method that we developed that detects FXIa in plasma samples as an FXIa-alpha 1-antitrypsin complex (FXIa-alpha 1AT). The presence and extent of CAD were documented by coronary angiography and assessed by a recently developed scoring system for semiquantitative estimation of coronary atherosclerosis. Plasma FXIa-alpha 1AT levels were significantly increased in patients with angiographically proven CAD (13.9 +/- 3.0 micrograms/L, n = 42) compared with age-matched, healthy control subjects (11.9 +/- 1.7 micrograms/L, n = 20) as well as patients with angiographically normal coronary arteries (12.0 +/- 2.3 micrograms/L, n = 25). Moreover, in the total patient population, the FXIa-alpha 1AT level was related to the number of significant coronary artery stenoses as well as to the total coronary score. FXIa-alpha 1AT showed a positive correlation with thrombin-antithrombin III complex, fibrinogen, and Lp(a) and an inverse correlation with apo A-I, as determined by multi-variate analysis. Our studies provide evidence that increased activation of the contact pathway occurs in patients with CAD and is related to the severity of the disease. Although it is unknown whether this abnormality is the cause or the result of the vascular lesion, it may be important for progression of the underlying atherosclerosis or for propagation of the atherosclerotic process itself.