In-vitro comparison of fondaparinux, unfractionated heparin, and enoxaparin in preventing cardiac catheter-associated thrombus

BACKGROUND: The Organization to Assess Strategies in Acute Ischemic Syndromes trials showed that fondaparinux (fonda) is at least as effective and safe as unfractionated heparin (UFH) and enoxaparin (enoxa) in acute coronary syndromes. Unexpectedly, there was an increase in catheter-related thrombus formation during percutaneous coronary interventions in fonda-treated patients. METHODS: Ten healthy male volunteers were pretreated with aspirin 500 mg 2 h before venesection of 50 ml of blood. Eight groups of anticoagulant (combinations) were tested and volunteers donated blood eight times, thus, acting as their own controls. The groups were UFH, UFH+eptifibatide, enoxa, enoxa+eptifibatide, fonda, fonda+eptifibatide, fonda+(half-therapeutic) UFH, and fonda+eptifibatide+(half-therapeutic) UFH. The blood/anticoagulant mix was kept at 37 degrees C and continuously circulated through a guiding catheter for 60 min or until the catheter became blocked with thrombus. Thrombus development was assessed by weighing each catheter before and after the procedure. Electron microscopy of the catheter lining was used to quantify the degree of erythrocyte and fibrin deposition. RESULTS: Despite fonda anticoagulation, catheters were invariably occluded by thrombus before the 60 min perfusion period had elapsed. Thrombotic catheter occlusion occurred even with higher fonda concentrations and combined fonda/eptifibatide use. All other combinations (including fonda and half-therapeutic UFH) ensured catheter patency for 60 min. Furthermore, thrombus weight and the cell/fibrinogen counts were significantly increased in fonda and fonda+eptifibatide compared with other treatment groups. CONCLUSION: Treatment with fonda, even in combination with eptifibatide, was not sufficient to prevent cardiac catheter thrombus development in our in-vitro study. However, the combination of fonda with 'half' therapeutic dosages of UFH were as efficient as other treatment strategies in preventing thrombus formation.