Enoxaparin-Associated Intracranial Hemorrhage Treated with Activated Factor VII

Objective: No specific agent exists to reverse hemorrhage in the setting of anticoagulation with low-molecular weight heparins (LMWH). Protamine is a specific antidote for heparin, but only partially effective for reversal of anticoagulation with LMWH. rFVIIa reverses anticoagulation with LMWH in vitro (1), but this application has not been studied in vivo. We report a case of life-threatening intracranial hemorrhage in a patient taking enoxaparin that was treated with recombinant activated factor VII (rFVIIa). Case report: A 62 year old woman with a history of breast cancer presented to the emergency department with sudden-onset of right-sided weakness. One week prior to presentation she was started on enoxaparin for the treatment of multiple thromboses related to therapy with bevacizumab, an antiangiogenesis adjunctive chemotherapy that increases the risk of both thromboembolic and hemorrhagic events. On presentation the patient was alert and without speech or cognitive deficits. Physical examination was unremarkable except for a dense right hemiparesis. CT of the brain demonstrated a left parietal mass with central bleeding. Immediate treatment included upright positioning and protamine sulfate 50 mg infused intravenously. Within hours the patient began to vomit and became somnolent MRI of the brain revealed increased bleeding with extension into the ventricles along with mid-line shift. The patient was given 4.8 mg rFVIIa and had surgical resection of the mass. No further bleeding was diagnosed post-operatively, and the patient was restarted on enoxaparin on postoperative day four. Conclusion: The utility of LMWH for patients at increased risk of hemorrhage is mitigated by a lack of effective reversal agents. rFVII may be considered with caution for the management of life-threatening bleeding in patients anticoagulated with LMWH if protamine and supportive measures fail. Further research is needed to determine the safety of this strategy, particularly in patients with complex hematologic disorders that may independently increase the risk of thrombotic complications.