Recombinant activated factor VII (rFVIIa) treatment in infants with hemorrhage

Background: Recombinant activated factor VII (rFVIIa) is approved by the FDA for the treatment of bleeding episodes in patients with hemophilia A or B with inhibitors to factor VIII or factor IX. In addition to the FDA-approved indications, rFVIIa has been anecdotally reported effective for profound bleeding episodes in adult patients without hemophilia, and proven beneficial for adults with intracranial hemorrhage. In the pediatric literature, case reports have been made with apparent clinical improvement seen after the use of rFVIIa for acute life-threatening bleeding; however, there are limited data regarding its use in infants < 4 months of age. We report our experience with rFVIIa in nine infants with severe hemorrhage of diverse etiologies. Methods: This case series of infants under 4 months with coagulopathy and bleeding treated with rFVIIa was collected from two institutions. We report the age, weight and pre-rFVIIa laboratory values of the patients as well as the clinical scenario and outcomes. Results: The nine infants all suffered acute life-threatening hemorrhage. Two patients were postoperative from cardiac surgery, two with Vitamin K deficiency and intracranial hemorrhage, three with suspected necrotizing enterocolitis and abdominal hemorrhage, and two with pulmonary hemorrhage. The patients ranged in age from 2 days to 4 months, (average age 1 month and average weight 3.3 +/- 1.0 kg). Seven of the nine patients had frozen plasma, cryoprecipitate, or platelet administration in failed attempts to correct the coagulation defect prior to receiving rFVIIa. The dose range used in this series was 90-100 mu g.kg(-1), with 90 mu g.kg(-1) being the most commonly used dose. The average pre-rFVIIa INR was 8.7 +/- 5.1. Four patients had an immeasurably high INR. All patients had clinical resolution of bleeding after receiving rFVIIa, and seven of nine patients survived. Conclusions: rFVIIa is a powerful hemostatic drug whose mechanism of action provides a theoretical specificity to sites of tissue injury. In addition to its FDA-approved uses in hemophiliac patients, this drug has a potential role in the treatment of life-threatening hemorrhage from multiple causes.