Bleeding and Thromboembolic Events after Termination of Therapy with Idraparinux for Prevention of Recurrent Venous Thromboembolism-Observation after the van Gogh Trials.

The long acting polymethylated antithrombotic compound Idraparinux has been investigated in the vanGogh trials for prevention of recurrent venous thromboembolism (VTE) using once weekly subcutaneous injections for 3–6 months (vanGogh PE and DVT trial) and for additional 6 months (vanGogh Extension trial). After termination of the studies Idraparinux was eliminated with a half live of 60 days or longer (Harenberg et al, submitted). We followed-up the patients (n=23) at our center for bleeding events, recurrent VTE and other severe events over 15 months. During the study period 2 major bleeding complications occurred in patients randomized to warfarin (days 70 and 186). During follow-up, 2 patients initially randomized to Idraparinux suffered from major bleeding events (days 65 and 140 during follow-up). Bleeding was related to an additional therapy of warfarin or low-molecular-weight heparin. At that time, the long elimination half life time of Idraparinux was unknown. One patient required continuation of anticoagulation due to homocygous factor V Leiden mutation and received warfarin starting one week after termination of idraparinux. At day 65 he was hospitalized because of a major intramuscular bleeding. One patient underwent total hip replacement at day 140 of follow-up receiving nadroparin for prophylaxis of VTE and developed a major postoperative bleeding with reoperation and transfusion. The concentrations of Idraparinux were 0,16μg/ml in each patient. Thereafter the long elimination time of Idraparinux was taken into consideration. In 1 of the patients warfarin was started at a 0.1μg/ml Idrparinux and titrated slowly into an INR range of 1.6 to 2.0 until Idrapaninux decreased to 0.05μg/ml. In the other patient postoperative prophylaxis of VTE was performed with LMWH at 0,01μg/ml Idraparinux (day 571 of follow-up). No adverse events occurred in both patients. During follow-up VTE occurred in 2 patients each initially randomized to warfarin (days 58 and 406) and Idraparinux (days 266 and 381), respectively. The concentrations of idraparinux were <0.01μg/ml in both patients. The data show that the very long half life of Idraparinux may lead to serious bleeding complications, if anticoagulation is given on top of the circulating compound within 3 or 4 months after termination of therapy. Cautious anticoagulation during this period may avoid bleeding. Recurrent VTE occurs late after termination of Idraparinux but in probably to the same frequence as after termination of warfarin.