Summary
Bivalirudin, a direct thrombin inhibitor binds specifically and reversibly to both
fibrin-bound and unbound thrombin. Bivalirudin is approved for use as an anticoagulant
in patients undergoing percutaneous coronary intervention. The OASIS-5 trial presented
a significant increase in cardiac catheter thrombosis for the pentasaccharid fondaparinux
compared to enoxaparin. Catheter thrombosis has never been reported in any trial using
bivalirudin. Our study compared the development of catheter thrombosis for bivalirudin,
enoxaparin, and unfractionated heparin in a controlled in-vitro environment. Ten healthy
male volunteers were pretreated with aspirin 500 mg 2 hours before venesection of
50 ml of blood. The seven groups of anticoagulant combinations tested were:UFH, UFH
+ eptifibatide, enoxaparin, enoxaparin + eptifibatide, bivalirudin bolus, bivalirudin
+ eptifibatide, bivalirudin bolus + continuous infusion. The blood/anticoagulant mix
continuously circulated through a cardiac guiding catheter for 60 minutes or until
the catheter became blocked with thrombus. Thrombus development was assessed by weighing
each catheter before and after the procedure. Electron microscopy was used to quantify
the degree of erythrocyte, platelet and fibrin deposition. Following anticoagulation
with bolus dose bivalirudin, the catheter was invariably occluded with thrombus after
33 minutes of circulation. However, a continuous infusion of Bivalirudin prevented
the development of occlusive catheter thrombosis. In the bolus bivalirudin group the
mean thrombus weight was significantly greater than in all other groups (p-value <
0.01 in all analyses). Bivalirudin given as a bolus was not sufficient to prevent
cardiac catheter thrombosis in our in-vitro study. However, a continuous infusion
of bivalirudin had similar anti-thrombotic efficacy compared to other treatment strategies.
Keywords
Cardiology - heparins - coagulation inhibitors - drug design - thrombosis
