Clinical Analysis Of Anticoagulant Therapy After Mechanical Heart Valve Replacement And Study Of The Role Of Thrombus Precursor Protein In The Monitoring Of Anticoagulation

Objective: The first part was to retrospectively analyze the clinical details of anticoagulation and the changes of coagulant parameters after mechanical heart valve replacement. The second part was designed to measure plasma thrombus precursor protein (TPP) concentration and international normalized ratio (INR) simultaneously in patients with mechanical heart valve prostheses, and then to explore the optimal anticoagulant therapeutic ranges. Methods: In the first part, complete data were available on 100 patients after mechanical heart valve replacements. The perioperative parameters including INR, TT, APTT, FIB were recorded and analyzed. Clinical manifestation and INR were collected, when the anticoagulant complications (thromboembolism or hemorrhage) occurred. The relevant risk factors were analyzed.In the second part, plasma TPP concentration and INR were measured in 60 patients with mitral valve prostheses and 20 other patients as the control. Plasma TPP concentration was assayed by enzyme linked immunosorbent method. The correlation between plasma TPP concentrations and INR levels was analyzed by linear regression. Plasma TPP concentrations and INRs in the anticoagulant patients were analyzed. Results: In the first part, cerebral thromboembolisms occurred in three patients and minor spontaneous bleeding events occurred in five patients after operations. While cerebral thromboembolism in one patient and bleeding in another one patient occurred, the INRs were in our predicted range (INR 1.5-2.0). While bleeding in one patient occurred, the INR was below 1.5. Thepatients after mitral valve replacements or after double valve replacements had higher plasma FIB concentrations than that of the patients undergoing aortic valve replacements. In the second part, no significantly statistical linear relationship was found between plasma TPP concentrations and INR levels. Plasma TPP concentrations were higher than 6μg/ml in 18 patients, who were considered at high risk of thromboembolism. The mean value of INRs was 1.59±0.58 in these patients. Of these patients, the INRs were in the predicted range (INR 1.5-2.0) in five patients, higher than 2.0 in three patients and below 1.5 in 10 patients. Minor spontaneous bleeding events occurred in 6 patients, who had higher mean INR value (2.27±2.05) and very low plasma TPP concentrations (0.77±0.40μg/ml). Of them, two patients' INRs were in our predicted range (INR 1.5-2.0), three patients' INRs were below 1.5, and only one's INR was higher than 2.0. There were 36 patients with plasma TPP concentrations below 6μg/ml (3.89±0.80μg/ml) and without spontaneous bleeding complications, who might be at the optimal anticoagulant state (INR 1.90±0.73). The 95% confidence of the mean INR value was 1.64-2.16. Their plasma TPP concentrations were in the range of 2.32μg/ml-5.46μg/ml. In the anticoagulant group, the patients with atrial fibrillation had higher plasma TPP concentrations than the patients with sinal rhythm.Conclusion: 1. The results of this study suggest that anticoagulant monitoring only by INR might have some limits. Our anticoagulant therapeutic range (INR 1.5-2.0) requires further evaluation. Patients after mitral valve or double valve replacements and/or with atrial fibrillation seem to be at higher risk of thromboembolism. 2. Our preliminary results suggest that INR between 1.64-2.16 and plasma TPP concentration between 2.32μg/ml-6μg/ml might be the optimal anticoagulant therapeutic range for patients with mechanical heart valveprostheses. Plasma TPP concentration is a valuable adjunct parameter in the anticoagulant monitoring. Especially, patients with very low plasma TPP concentrations might be predisposed to high risk of spontaneous bleeding.