Management of Intractable Bleeding after Cardiac Surgery with Recombinant Activated Factor VII

Background Intractable hemorrhage is a dreaded complication after cardiovascular surgery often requiring re-exploration and the administration of large quantities of blood products. In view of problems with aprotinin, a new safer effective agent is needed. Recombinant activated FVII is approved for use in patients with hemophilia A and B who have inhibitors to factors VIII and IX, and has shown promise in off-label use for the management of life-threatening hemorrhage in several clinical scenarios including cardiac surgery. It may help control bleeding, reduce blood product usage, and avoid potential morbidity. Its exact place in the management of bleeding during and after cardiac surgery is not yet fully known.

Methods. We performed a retrospective review of patients who were given recombinant factor VIIa (rFVIIa; Novoseven, NovoNordisk, Copenhagen, Denmark) to control bleeding after major cardiovascular surgery requiring cardiopulmonary bypass (CPB) at our institution. The decision to administer rFVIIa was made empirically based on the observation by the surgeons of refractory bleeding that appeared unresponsive to conventional hemostasis agents including the requirement of large volumes of blood components, and was at least severe enough to prevent chest closure. We compared blood loss and blood component usage in patients before and after rFVIIa. We also performed a detailed review of the English literature to determine the role of rFVIIa in the treatment of bleeding after cardiac surgery.

Results. Between August 2002 to February 2006, 1295 patients underwent open heart surgery at our institution; of these, 28 were given Novoseven either to control intractable bleeding, or to prevent major bleeding. Table 1 shows the patient characteristics. Satisfactory hemostasis was achieved in all but 3 patients after a single 90 μg/kg intravenous dose of rFVIIa. In all patients, there was a dramatic reduction in the amount of blood components (PRBCs, Platelets and FFP) used after rFVIIa infusion (Table 2). Cryoprecipitate was administered routinely with rFVIIa and its usage did not change significantly (Table 2). No thromboembolic or other complications directly related to rVIIa occurred.

Conclusions. We have demonstrated that intravenous rFVIIa is effective, safe, and valuable in the management of intractable bleeding after complicated cardiac surgeries. There are several reports and reviews in the literature which corroborate our experience and indicate that recombinant factor VIIa is a potent pro-hemostatic agent which has a role in the treatment of life-threatening refractory hemorrhage associated with cardiac surgery. Earlier preemptive administration of rFVIIa during or before surgery may be of value in patients at high risk of intractable bleeding in order to limit blood loss, and to avoid potential morbidity from large volume blood component transfusions. Randomized, controlled trials are warranted to assess the efficacy, safety, and cost-benefit of this intervention in cardiac surgical patients.

TABLE 1. Characteristics and operative course of the 28 patients Mean age 60 yrs (range 22–85) Male, M 24(85%); F 4(15%) Total number of surgical procedures performed: 34 Aortic valve: 7; Bentall or modified Bentall: 9 (3 emergent) Mitral Valve Replacement: 4; CABG: 10; Redo 2 Left pneumonectomy/resection of L Atrial cuff & pericardium: 1 Removal of Inferior vena cava tumor (Renal cell ca):

1. Re-exploration: 6; Delayed closure: 5; Both re-exploration and delayed closure:

2. Median bypass time: 214 min (65–358)

Timing of Novoseven: intra op: 21 including elective use in 2 pts; post op: 7 Dose of Novoseven: 90mcg/kg in 22; 45 mcg/kg 2 patients Responders 25(89%) Outcome: Deaths 11(38%) Autopsies: 2; no evidence of systemic thrombosis

Table 2. Details of the blood products administered both before and after rFVIIa infusion.