Safety of activated recombinant factor VII in patients with circulatory assist devices

Introduction

Recombinant activated factor VII (rFVIIa; Novoseven) is indicated for treatment of bleeding in hemophilic patients with antibodies against factor VIII or factor IX. Although not licensed or agreed for other use, it is increasingly reported for refractory hemorrhage. Implantation of a circulatory assist device requires tight anticoagulation therapy and may be complicated by massive bleeding. We report our experience with off-label use of rFVIIa in nine patients with circulatory assistance.

Methods

We retrospectively reviewed all patients treated with rFVIIa for massive bleeding secondary to anticoagulation during circulatory assistance between March 2004 and November 2008. rFVIIa use and dosage was decided according to local guidelines when available (released in May 2006). According to these guidelines, systematic crosscheck for active correction of hypothermia, acidosis, and coagulation factors with parallel consideration for any feasible interventional embolisation or haemostatic surgery are required for authorization of rFVIIa use.

Results

Nine patients with circulatory assistance received rFVIIa. Median patient age was 43 years (<1 to 55). Eight patients underwent cardiac surgery (including two heart transplants). One had a bipulmonary transplant. The device was an extracorporeal membrane oxygenator in seven patients and a ventricular assist device in two patients. Median rFVIIa dose was 100 μg/kg (45 to 180), split into two or three injections in six cases. Bleeding control was obtained in five patients (60%). The mortality rate at 30 days was 40%, including two within 48 hours from failure to control hemorrhage. We observed one thromboembolic complication (stroke) which may potentially be related to rFVIIa administration.

Conclusion

Our series suggests that the cautious use of rFVIIa may be an option in patients with a circulatory assist device suffering from massive hemorrhage refractory to conventional treatment.