Patients requiring interruption of long-term oral anticoagulant therapy: the use of fixed sub-therapeutic doses of low-molecular weight heparin

Introduction: We tested the efficacy and safety of fixed doses of Low-Molecular Weight Heparin (LMWH) in patients requiring interruption of Vitamin-k Antagonist (VKA) because of invasive procedures Methodology: Pre-operatively, patients discontinued VKA 5 +/- 1days; in those at low-risk for thrombosis, LMWH was given at a prophylactic dosage of 3.800 U.I. (nadroparin) or 4.000 U.I. (enoxaparin) anti-FXa once daily the night before the procedure. In patients at high-risk for thrombosis, LMWH was started early after VKA cessation and given at fixed sub-therapeutic doses (3.800 or 4.000 UI anti-FXa twice daily) until surgery. Post-operatively, LMWH was reinitiated 12 hours after procedure while VKA the day after. Heparin was continued until a therapeutic INR value was reached. The primary efficacy endpoints were the incidence of thromboembolism and major bleeding from VKA suspension (because of surgery) to 30 +/- 2 days post-procedure. Results: A total of 328 patients (55.4% at low-risk and 44.6% at high-risk for thrombosis) were enrolled; 103 (31.4%) underwent major surgery and 225 (68.6%) non major invasive procedures. Overall, thromboembolic events occurred in 6 patients (1.8%, 95% confidence intervals 0.4 to 3.2), 5 belonging to high-risk and 1 to low-risk group. Overall, major bleeding occurred in 7 patients (2.1%, 95 CI 0.6 to 3.6), 6 patients belonged to high-risk and 1 to low-risk group; most of events occurred in high-risk group during major surgery. Conclusion: LMWH given at fixed sub-therapeutic doses appears to be a feasible and safe approach for bridging therapy in chronic anticoagulated patients. Summary. Introduction: We tested the efficacy and safety of fixed doses of low-molecular-weight heparin (LMWH) in patients requiring interruption of vitamin-K antagonist (VKA) because of invasive procedures. Methodology: Preoperatively, patients discontinued VKA for 5 +/- 1 days; in those at low risk for thrombosis, LMWH was given at a prophylactic dosage of 3800 UI (nadroparin) or 4000 UI (enoxaparin) anti-factor (F) Xa once daily the night before the procedure. In patients at high risk for thrombosis, LMWH was started early after VKA cessation and given at fixed sub-therapeutic doses (3800 or 4000 UI anti-FXa twice daily) until surgery. Postoperatively, LMWH was reinitiated 12 h after procedure while VKA was reinitiated the day after. Heparin was continued until a therapeutic INR value was reached. The primary efficacy endpoints were the incidence of thromboembolism and major bleeding from VKA suspension (because of surgery) up to 30 +/- 2 days postprocedure. Results: A total of 328 patients (55.4% at low risk and 44.6% at high risk for thrombosis) were enrolled; 103 (31.4%) underwent major surgery and 225 (68.6%) non-major invasive procedures. Overall, thromboembolic events occurred in six patients (1.8%, 95% confidence interval 0.4-3.2), five belonging to the high-risk group and one belonging to the low-risk group. Overall, major bleeding occurred in seven patients (2.1%, 95 confidence interval 0.6-3.6), six patients belonged to the high-risk group and one belonged to the low-risk group; most of the events occurred in the high-risk group during major surgery. Conclusion: LMWH given at fixed sub-therapeutic doses appears to be a feasible and safe approach for bridging therapy in chronic anticoagulated patients