Efficacy of recombinant activated factor VII in the management of severe hemorrhage following cardiac surgery

Introduction

Severe bleeding after cardiac surgery is often difficult to manage. The efficacy of traditional drugs vary, which is why it is necessary to use newer agents for beneficial control and prevention of massive bleeding. The aim of this study is clinical evaluation of the efficacy of recombinant activated factor VII (rFVIIa) in the treatment of bleeding during and after cardiac surgery by stimulation of clot formation at the site of injury.

Patients and methods

rFVIIa (NovoSeven^®; Novo Nordisk, Bagsvaerd, Denmark) was used in 37 adult patients aged between 49 and 68 years who underwent open heart surgery (10 patients coronary surgery, five patients valvular surgery, six patients surgery of congenital heart defects, three patients surgery of dilated cardiomyopathy) or surgery for aortic aneurisms (13 patients) in 2002–2005. All patients had normal coagulation parameters before surgery. In these patients, bleeding (10–20 ml/min) has developed intraoperatively or postoperatively. In 21 patients the bleeding started after surgery intraoperatively, and in 16 patients severe hemorrhage developed in the postoperative period. Treatment of bleeding included infusions of fresh frozen plasma, platelet concentrate, aprotinin and μ-aminocaproic acid. Two patients underwent surgical re-exploration for bleeding. However pharmacological and surgical management failed to stop the hemorrhage. Prior to administration of rFVIIa, blood loss reached 2.5–3 l in some patients. rFVIIa was administered in doses of 60–90 μg/kg body weight. We used Student's t test for statistical analysis the laboratory data prior to and after rFVIIa.

Results

After administration of the first median dose (75.3 ± 10.1 μg) rFVIIa bleeding stopped in 27 patients (74%), and markedly decreased in four patients during 1 hour. Six patients who did not benefit from initial rFVIIa administration received additional drug in doses of 70–90 μg/kg, with good results in four patients. (Five patients received one additional dose, one patient received four doses.)

There was considerable reduction in the need for replacement therapy after rFVIIa administration. Analysis of laboratory data (Table 1) revealed a significant decrease of prothrombin time after 30 min and improvement of platelet function after 3 hours of rFVIIa administration. There were no significant differences in the dynamics of other parameters of hemostasis. Adverse events have not been seen after drug injection.

Table 1

Conclusion

These results suggest that rFVIIa has high efficacy in treatment of massive hemorrhage and reducing the need for hemotransfusions when other hemostatic therapy has failed.