Effect of warfarin on regional left atrial coagulation activity in mitral stenosis

Increased regional left atrial (LA) coagulation activity has recently been implicated in the pathophysiology of LA thrombus and systemic embolism in mitral stenosis (MS). Anticoagulation with warfarin reduces the risk of such thromboembolism, but the effect of warfarin on LA coagulation activity is unknown. We have addressed this question in MS patients with normal or prolonged clotting times. Peripheral venous and LA coagulation activities were measured in MS patients on long-term oral anticoagulation, who were predisposed to increased LA coagulation activity because of the presence of LA spontaneous echo contrast. Patients ceased warfarin 4 days before percutaneous balloon mitral valvuloplasty, and had either a normal (n = 15) or prolonged (n = 8) International Normalized Ratio (INR) at valvuloplasty. Coagulation activity was assessed during the valvuloplasty procedure, but before valve dilation, by measuring levels of prothrombin fragment 1 + 2 (F1 + 2), a marker of thrombin generation. The LA F1 + 2 level exceeded the peripheral venous level in patients with a normal INR (p <0.001), but these levels were similar in patients with a prolonged INR (p = 0.16). Moreover, the LA (p <0.005) and peripheral venous (p <0.03) F1 + 2 levels, as well as the LA-peripheral venous F1 + 2 difference (p <0.03) were lower in patients with a prolonged INR. These results suggest that anticoagulation with warfarin in MS not only reduces systemic coagulation activity but is associated with a greater reduction in LA coagulation activity. The latter may contribute to the reduced risk of LA thrombus formation that accompanies warfarin therapy in MS.