Off-label use of recombinant factor VIIa for treatment of haemorrhage: results from randomized clinical trials

BACKGROUND: Recombinant factor VIIa (rFVIIa) is used for haemophilic patients with inhibitors against coagulation factor VIII or IX, but there is also an off-label use of rFVIIa for patients with massive bleeding. The aim of the present study was to review the randomized clinical trials (RCT) for evidence of such an approach.

METHODS: In October 2007, a review of RCT involving rFVIIa for non-haemophilic indications was performed. The effect of rFVIIa on blood loss and transfusion requirements was recorded.

RESULTS: Seventeen RCTs were identified concerning different bleeding conditions, for example, secondary to surgery, infection and stem cell transplantation. Three pilot studies reported a significant reduction in transfusion requirements and/or blood loss in the rFVIIa-treated groups, but these have not been confirmed in large randomized trials. No difference in thromboembolic complications between rFVIIa and placebo-treated patients were found, except for a study in patients with intracranial haemorrhage. In the intracranial haemorrhage study, 16 out of 16 arterial thrombotic events and 19 out of 21 combined arterial and venous thromboembolic events were found in the rFVIIa-treated patients.

CONCLUSION: There is little evidence to support routine use of rFVIIa for patients with massive bleeding based on the results of the randomized trials performed. In patients with a normal haemostatic system, administration of rFVIIa may be associated with an increased risk of thromboembolic events.