Treatment of refractory bleeding after cardiac operations with low-dose recombinant activated factor VII (NovoSeven®): a propensity score analysis

Background: Recombinant activated factor VII (rFVIIa) has been increasingly used to stop life-threatening bleeding following cardiac operations. Nonetheless, the issue of dosing, given the expense and potential for thrombotic complications, is still of major concern. We report our experience with small-dose rFVIIa in patients with refractory bleeding after cardiac surgery. Methods and results: From September 2005 to June 2007, 40 patients (mean age 70.1 ± 9.2 years, 52.5 males) received a low dose of rFVIIa (median: 18 μg/kg, interquartile range: 9-16 μg/kg) for refractory bleeding after cardiac surgery. Forty propensity score-based greedy matched controls were compared to the study group. Low dose of rFVIIa significantly reduced the 24-h blood loss: 1610 ml [ 1285-1800 ml] versus 3171 ml [2725-3760 ml] in the study and control groups, respectively (p <0.001). Thus, hourly bleeding was 51.1 ml [34.7-65.4 ml] in patients receiving rFVIIa and 196.2 ml/h [142.1-202.9 ml] in controls (p <0.001). Furthermore, patients receiving rFVIIa showed a lower length of stay in the intensive care unit (p <0.001) and shorter mechanical ventilation time (p <0.001). In addition, the use of rFVIIa was associated with reduction of transfusion requirements of red blood cells, fresh frozen plasma and platelets (all, p <0.001). Finally, treated patients showed improved hemostasis with rapid normalization of coagulation variables (partial thromboplastin time, international normalized ratio, platelet count, p <0.001). In contrast, activated prothrombin time and fibrinogen did not differ between groups (p = ns). No thromboembolic-related event was detected in our cohort. Conclusions: In our experience low-dose rFVIIa was associated with reduced blood loss, improvement of coagulation variables and decreased need for transfusions. Our findings need to be confirmed by further larger studies.