Reversal of low-molecular-weight heparin-induced bleeding in patients with pre-existing hypercoagulable states with human recombinant activated factor VII concentrate

Low-molecular-weight heparins are widely employed in prophylactic and therapeutic antithrombotic regimens for venous thromboembolic events. Excessive anticoagulation with low-molecular-weight heparins rarely can precipitate catastrophic bleeding complications. Currently, there is no specific or reliable antidote that can reverse the anticoagulant effects of low-molecular-weight heparins efficiently and safely. This report describes three individuals with underlying hypercoagulable states, who developed clinically significant bleeding complications while receiving therapeutic anticoagulation with enoxaparin. All of the hemorrhagic events subsequently were safely and effectively reversed with a single intravenous bolus infusion of recombinant activated factor Vila (RFVIIa) concentrate. Hemoglobins, prothrombin times, and clinical overt bleeding were monitored before and after the administration of RFVIIa. In all three cases, bleeding was controlled without an increase in thrombotic events. Our findings demonstrate that RFVIIa can rapidly and safely reverse the hemorrhagic adverse effects associated with excessive levels of low-molecular-weight heparin in patients with pre-existing hypercoagulable conditions and/or acute venous thromboembolism.