Elsevier

Mayo Clinic Proceedings

Volume 79, Issue 12, December 2004, Pages 1495-1500
Mayo Clinic Proceedings

Original Article
Recombinant Factor VIIa for Rapid Reversal of Warfarin Anticoagulation in Acute Intracranial Hemorrhage

https://doi.org/10.4065/79.12.1495Get rights and content

OBJECTIVE

To assess the effects of recombinant factor VIIa (rFVIIa) on hemorrhage volume and functional outcomes in warfarin-related acute intracranial hemorrhage (ICH), which has a 30-day mortality of more than 50%.

PATIENTS AND METHODS

We reviewed the clinical, laboratory, and radiographic features of a consecutive series of 7 patients (median age, 87 years; 5 women) with symptomatic, nontraumatic warfarin-related acute ICH treated with intravenous rFVIIa at St. Luke's Hospital in Jacksonville, Fla, between December 2002 and September 2003. Prestroke baseline functional status was assessed with the modified Rankin Scale. Outcome was assessed with the Glasgow Outcome Scale.

RESULTS

The international normalized ratio decreased from a mean of 2.7 before administration of rFVIIa to 1.08 after administration of rFVIIa. The median prestroke score on the modified Rankin Scale was zero. The median presenting score on the Glasgow Coma Scale was 14 (range, 4-15). The mean time from onset to treatment was 6.2 hours. The mean initial dose of rFVIIa was 62.1 μg/kg. One patient underwent placement of an external ventricular drain, and another underwent craniotomy and hematoma evacuation. Five of the 7 patients survived and were dismissed from the hospital with severe disability (Glasgow Outcome Scale, 3); 2 patients died during hospitalization.

CONCLUSIONS

Intravenous bolus administration of rFVIIa can rapidly lower the international normalized ratio and appears to be safe for patients with warfarin-related ICH. Prospective controlled studies are needed to determine whether rFVIIa can prevent hematoma expansion and improve neurologic outcomes in patients with warfarin-related ICH.

Section snippets

PATIENTS AND METHODS

We reviewed the clinical, laboratory, and radiographic features of a consecutive series of 7 patients who had symptomatic, nontraumatic, warfarin-related acute ICH treated with rFVIIa at St. Luke's Hospital in Jacksonville, Fla, between December 2002 and September 2003. This study was approved by the Mayo Foundation Institutional Review Board.

Of the 7 patients in our study (mean age, 83.5 years; median age, 87 years; range, 70-92 years), 5 were women. Four patients had intraparenchymal

RESULTS

The median prestroke score on the modified Rankin Scale was zero (range, 0-2). Six patients were taking warfarin for chronic atrial fibrillation and 1 patient for deep venous thrombosis and pulmonary embolus. Five patients had a history of hypertension. No patient had a history of ischemic stroke, Alzheimer disease, or mild cognitive impairment. One patient had a history of carcinoma (prostate cancer status after radical prostatectomy with undetectable prostate-specific antigen). The mean INR

DISCUSSION

Factors that predict a worse outcome in ICH include hematoma volume, IVH, and a depressed level of consciousness.1 Early hemorrhage growth of more than 33% of baseline volume occurs within 24 hours in at least 38% of patients and is associated with neurologic deterioration.15 No surgical or medical intervention has been proved to reduce morbidity and mortality. Emergent hematoma evacuation (within the first 3-4 hours) is often delayed by standard anticoagulation reversal methods, thereby

CONCLUSIONS

Compared with conventional treatment with FFP and vitamin K, intravenous bolus administration of rFVIIa clearly leads to rapid correction of the INR in patients taking warfarin without risk of hypervolemia and anaphylaxis. Thus, rFVIIa can expedite safe neurosurgical hematoma evacuation. What is less clear is whether emergent use of rFVIIa can improve neurologic and functional outcomes with or without hematoma evacuation. The therapeutic time window for rapid warfarin reversal is also unclear

Acknowledgments

We thank Darlene E. Gunsolus for her assistance with the preparation of the submitted manuscript.

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    Presented in part at the 29th International Stroke Conference, San Diego, Calif, February 5 to 7, 2004.

    Dr Brott has served on the Data and Safety Monitoring Board of a randomized clinical trial sponsored by Novo Nordisk (Princeton, NJ) of recombinant factor VIIa (NovoSeven) for spontaneous intracerebral hemorrhage.

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