Reversal for heparins and new anticoagulant treatments

Even with unfractionated heparin or derivates, the reversal of pharmacologic anticoagulation is crucial in anticoagulated patients developing a life-threatening bleeding or scheduled for an emergency procedure. The antagonisation of unfractionated heparin is well codified: each milligram of protamine sulfate antagonizes 100 IU of heparin. Measurement of thrombin time reflects the anti-IIa effect of heparin and has to be monitored immediately and 1hour after the injection of protamine. The required dose of protamine sulfate depends on dosage and time of LMWH administration, although no clinical study supports these data. To date, there is no effective antidote for new anticoagulants (fondaparinux and other pentasaccharides, direct thrombin inhibitors, direct anti-Xa inhibitors). Some preliminary studies suggest the effectiveness of recombinant activated factor VII for pentasaccharides and activated or not Prothrombin Complex Concentrates and recombinant activated factor VII for oral anti-Xa and anti-IIa agents. Therefore, while the characteristics of these new anticoagulants could increase the comfort and improve the compliance, their development needs to ascertain the lack of increase in bleeding complications and the need for a safe and effective antidote.