Fondaparinux for the Treatment of Recurrent Venous Thromboembolism During Low Molecular Weight Heparin Therapy: A Retrospective Case Series.

Fondaparinux is a synthetic pentasaccharide that exerts its anticoagulant effects by indirectly inhibiting Factor Xa. Large randomized controlled multicenter trials have shown that daily administered subcutaneous fondaparinux at specified weight based dosing is as effective as unfractionated heparin (UFH) and low molecular weight heparin (LMWH) for the initial treatment of venous thromboembolic events (VTE), in conjunction with warfarin. In the case of recurrent DVT or PE, however, there is no standard of care and optimal anticoagulation still remains a challenge. Based on limited data, most patients on warfarin with recurrent VTE would be switched to LMWH or UFH, but the use of fondaparinux in this setting is limited to anecdotal experience.

We report the Indiana University experience with the use of fondaparinux for recurrent DVT or PE, failing therapy with LMWH. This is a retrospective review of 13 patients with recurrent thromboembolism, studied in two hospital settings. The mean age was 37 years (range 23-65), there were 8 females and 5 males, and all the patients had failed enoxaparin (two patients had also progressed on tinzaparin). The underlying medical conditions that predisposed to thromboses varied: sickle cell disease (3), antiphospholipid syndrome (3), cancer (3), May Thurner syndrome (1), and 3 patients with inherited thombophilia (Antithrombin III deficiency, Factor V Leiden and Prothrombin 20210 Gene Mutation). Mean weight was 90.7 kg (range 52-150). Mean time to recurrence on LMWH was 330 days. Fondaparinux was prescribed at 7.5mg daily or 10mg daily, based on body weight. Anti-Factor Xa levels were measured in at least half of the patient population, and response was assessed by clinical improvement or progression.

Thirty one percent (4/13) of patients had recurrent thromboembolic episodes (response rate 69%). Time to progression during therapy with fondaparinux was available on 2/4 patients, and was 17 months (range 13-21). No adverse events including bleeding complications or death were reported.

Fondaparinux may have efficacy in the treatment of recurrent VTE that has progressed on LMWH. These results are hypothesis generating and should be evaluated prospectively.

No relevant conflicts of interest to declare.