BACKGROUND Recent evidence suggests that regional left atrial coagulation activity may be increased in mitral stenosis and perhaps contribute to the pathophysiology of left atrial thrombus. However, the relation of left atrial coagulation activity to factors that predispose to left atrial thrombus formation is unknown, and the relation between left atrial and systemic coagulation activities is unresolved. RESULTS Left atrial and peripheral venous levels of the coagulation marker prothrombin fragment 1 + 2 (F1 + 2) were measured in 32 patients with mitral stenosis with normal clotting times and no left atrial thrombus who were undergoing percutaneous balloon mitral valvuloplasty. Baseline peripheral venous F1 + 2 levels, measured at the beginning of the valvuloplasty procedure, did not differ from those of 30 age-matched control patients. Prevalvuloplasty left atrial F1 + 2 levels, obtained immediately after transseptal puncture, were similar to femoral venous levels in patients without left atrial spontaneous echo contrast (LASEC) (0.81 +/- 0.32 versus 0.81 +/- 0.27 nmol/L, n = 7) but greater than femoral venous levels in patients with LASEC and either sinus rhythm (1.57 +/- 0.86 versus 0.99 +/- 0.38 nmol/L, n = 16, P < .001) or atrial fibrillation (1.52 +/- 0.69 versus 0.85 +/- 0.33 nmol/L, n = 9, P < .003). Furthermore, LASEC emerged as the only significant predictor of increased regional left atrial coagulation activity (P = .005) on stepwise multivariate logistic regression analysis. CONCLUSIONS Increased regional left atrial coagulation activity in mitral stenosis occurs in the presence of LASEC, is evident in either sinus rhythm or atrial fibrillation, and is associated with normal systemic coagulation activity.