A prospective pilot study of prophylactic treatment of preterm neonates with recombinant activated factor VII during the first 72 hours of life

Objective., Intraventricular hemorrhage (IVH) in the preterm infant is a devastating complication, causing marked mortality and morbidity. A general hemostatic agent such as recombinant activated factor VII (rFVIIa) might have the potential to reduce the extent of severe IVH. Design. Prospective, single-arm pilot study. Setting. Level III neonatal intensive care unit. Patients. Ten preterm infants between 23 and 28 wks of gestation. Intervention: Administration of a 100-mu g/kg rFVIIa bolus injection within the first 2 hrs of life, followed by 100 mu g/kg rFVIIa every 4 hrs, for the first 72 hrs of life. Measurements and Main Results. Cranial ultrasonography and flow studies of the major arteries and the venae cava, aorta, vena portae, and venae renales, was performed at study enrollment and at 12 hrs, 24 hrs, 48 hrs, and 72 hrs. Blood cell counts and coagulation studies were performed. End points of the study were occurrences of adverse events, with an emphasis on thrombotic events or disseminated intravascular coagulation (DIC). Ten preterm infants with a gestational age of 23 wks 1 day to 28 wks 3 days were included. None had venous thrombosis or cerebral infarction during or after the treatment. Neither platelet consumption nor DIC was observed. Two infants with an umbilical artery catheter had a thrombus at the catheter tip (one during infusion of the study drug), which was successfully treated with heparin. One had grade III IVH and died on day 6 of life; in another, grade II IVH progressed to grade III after termination of the drug. Conclusion, One hundred mu g/kg rFVIIa does not accumulate if administered prophylactically to preterm infants of <28 wks of gestation every 4 hrs in the first 72 hrs of life. In this population, rFVIIa does not cause DIC. Thrombus formation was observed in two infants with umbilical artery catheters but in none of the infants with venous catheters. Embolic events were not observed. In this pilot study, which did not provide the sample size to assess any effect of rFVIIa on the incidence of IVH, 20% of the neonates went on to have grade III or IV IVH, which is similar to the rate in studies in which rFVIIa was not given.