EFFECTS OF WARFARIN THERAPY ON PLASMA-FIBRINOGEN, VON-WILLEBRAND-FACTOR, AND FIBRIN D-DIMER IN LEFT-VENTRICULAR DYSFUNCTION SECONDARY TO CORONARY-ARTERY DISEASE WITH AND WITHOUT ANEURYSMS

Cardiac impairment in patients is associated with intracardiac thrombus formation and thromboembolism. A high prothrombotic state may exist in such patients, and abnormalities in plasma markers of thrombogenesis may be indicative of such a state. The aim of this study wets to determine the associations of left ventricular (LV) aneurysm formation and dysfunction with plasma fibrinogen, van Willebrand factor, and fibrin D-dimer, which are markers associated with thrombus formation (thrombogenesis) and to investigate the effects of warfarin given to patients with LV aneurysms on fibrinogen and D-dimer levels. A. cross-sectional study of 112 patients with coronary artery disease was initially per formed: 34 patients had normal LV function (group 1); 30 had LV dysfunction without aneurysm formation (group 2); 29 had LV aneurysms without anticoagulation (group 3a); and 19 patients had LV aneurysms with warfarin therapy (group 3b). Results were compared with 158 population controls from a random population sample. A longitudinal study of 10 patients given warfarin was also performed. In group 1, plasma fibrinogen (median difference 0.36 g/L; p = 0.0009) and van Willebrand factor (median difference 17 IU/dl; p = 0.04) were elevated, whereas plasma D-dimer levels (median difference 23.0 ng/ml; p = 0.001) were lower than those in population control subjects. There were no significant differences in plasma fibrinogen, von Willebrand factor, or D-dimer levels between groups 1 and 2. In group 39, plasma fibrinogen was elevated when compared with group 1 (median difference 0.6 g/L; p = 0.0001), with a trend toward high von Willebrand factor levels. In these patients, plasma D-dimer levels were also elevated when compared with group 1 (median difference 55 ng/ml; p = 0.0007). In similar patients taking warfarin (group 3b), there was no significant difference in plasma fibrinogen, but there was a lower plasma fibrin D-dimer level when compared with group 39 (median difference 65.5 ng/ml; p = 0.0003). In the longitudinal study, there was a reduction in median plasma fibrin D-dimer levels 2 months after administering warfarin (148 vs 61 ng/ml; paired Wilcoxon test, p = 0.01). This reduction in plasma fibrin D-dimer with warfarin is consistent with the beneficial effect of warfarin therapy in reducing thromboembolic risk. The measurement of plasma fibrin D-dimer may thus be useful as a marker of ongoing intravascular thrombogenesis, allowing identification of high-risk patients. This may aid in decision-making when warfarin therapy is being considered.