Very low-dose recombinant activated factor VII for treatment of major surgical bleeding

T. Hoffmann, S. Sixt, A. Albert, A. Dierksen, E. Roussel, A. Lichtenberg, A. Assmann (Duesseldorf, Germany)

Bleeding Disorders - Clinical Studies
Date: 18.02.2017,
Time: 08:30 - 09:45

Objective: Recombinant activated factor VIIa (rFVIIa) is widely used for treatment of major traumatic bleeding beyond its labelled indications. However, conflicting data have been presented with respect to thrombotic risks. Our study evaluates the safety and efficacy of single shot very low-dose rFVIIa (vld-rFVIIa) in cardiosurgical patients.

Methods: Real-time monitoring of relevant hemostatic parameters was conducted in a prospective cohort study of patients with high risk for major hemorrhage during open heart surgery (n=281). First-step bleeding therapy was carried out by goal directed substitution of hemostatic compounds according to a standardised algorythm. In case of unabated bleeding following substitution single shot vld-rFVIIa (<=20micrograms/kg bodyweight) was administered (n=167). Morbidity and mortality as well as hemostatic efficacy in the vld-rFVIIa group was compared to patients without rFVIIa administration (n=114).

Results: Neither the risk of thromboembolic complications (6.6% with versus 9.7% without vld-rFVIIa administration; p=0.372) nor the 30d- (4.4% versus 7.3%; p=0.418) or 1yr-mortality (14.4% versus 19.3%; p=0.325) in vld-rFVIIa patients was increased as compared to patients without rFVIIa. Hemostatis was achieved by single shot vld-rFVIIa in 61.3% (1st substitution level) and 88.6% (2nd substitution level) of patients, respectively without need for further hemostatic treatment. Clinical efficacy could be objectified by laboratory testing (subgroup of n=29 patients), as clotting times of the extrinsic pathway were significantly shortened by vld-rFVIIa administration (prothrombin time -5±1sec / Quick +59±13%; extrinsic clotting time by thrombelastometry -13±11sec).

Conclusion: According to our prospective cohort study, very low-dose recombinant activated factor VII on top of goal directed substitution therapy is both safe and effective in cardiosurgical patients with unabated bleeding.