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Objective: To explore the role of thrombus precursor protein (TpP) in assessment of anticoagulation and predict the risk of thromboembolism in the patients with atrial fibrillation (AF) after mechanical heart valve replacement. Methods: TpP plasma concentration and international normalization ratio (INR) were measured in 45 patients with atrial fibrillation and 45 patients with sinus rhythm both after mechanical heart valve replacement. Twenty patients with non-valvular heart diseases were selected as the control. Furthermore, the patients with AF were divided into groups based on different TpP plasma concentration and TpP plasma concentration and INR were analyzed. Results: After mechanical heart valve replacement, those with AF had higher TpP plasma concentration than those with sinus rhythm. It was found that discordancy existed between INR and TpP plasma concentration in the patients with AF. There were 28 AF patients with TpP plasma concentration lower than 6 μg/ml and without bleeding, who might be at the optimal anticoagulant state. The 95% confidence of the mean INR value was 1.90-2.30 in these patients and TpP plasma concentration was between 2.84-5.74 μg/ml. Conclusion: Patients with AF might face higher risk of thromboembolism after mechanical valve replacement; INR between 1.90-2.30 and TpP plasma concentration between 2.84-6 μg/ml might be the optimal anticoagulant range for patients with AF after mechanical valve replacement.