Prevention of intraventricular haemorrhage: A role for recombinant activated factor VII?

Abstract

As the survival from extreme prematurity continues to improve, focus on the quality of this survival becomes increasingly important. Prevention of intraventricular haemorrhage (IVH) and its potential long-term sequelae remains one of the major challenges in the early management of these infants. Recombinant activated factor VII (rVIIa), a novel haemostatic agent with an ever-expanding list of potential applications, warrants consideration for use in this setting. This review examines the pathogenesis and prevention of IVH, current concepts of haemostasis both in adults and neonates, and the postulated mechanism of action and various uses of rVIIa. Published data specifically relating to use of rVIIa in neonates is summarised. The hypothesis that early (prophylactic) administration of rVIIa to extremely preterm infants (<28 weeks) would reduce the incidence of severe IVH is explored.

The Diagnosis, Management, and Postnatal Prevention of Intraventricular Hemorrhage in the Preterm Neonate

“…Since evidence suggests that Factor VII may be an effective agent in prevention of bleeding in a diverse array of situations, it has also been proposed as a potential treatment for IVH 77. Since factor VII is thought to require exposed tissue factor or activated platelets in order for it to promote coagulation, it is thought that the pro-thrombotic effects of factor VII should be restricted to the site of injury, thus contributing to its safety.…”

“…Since factor VII is thought to require exposed tissue factor or activated platelets in order for it to promote coagulation, it is thought that the pro-thrombotic effects of factor VII should be restricted to the site of injury, thus contributing to its safety. Administration just after onset of IVH would be expected to promote clotting in the periventricular region without promoting a hypercoagulable state 77. While results with factor VII in non-hemophiliac patients are preliminary and further study is necessary, its proposed mechanism of action, positive results in some patient populations with major bleeding, and the observed safety so far in the admittedly small number of neonates in which it has been assessed, suggest that this is an intervention which deserves further study in the setting of IVH.…”

Rol del factor VII recombinante activado en pacientes neuroquirúrgicos y neurocríticos

“…Por otro lado, el fármaco puede favorecer la liberación de citoquinas proinflamatorias 87 . Los eventos trombóticos se han situado en torno al 1-2% en los pacientes hemofílicos 77,85 , aunque la incidencia parece mayor en las indicaciones "off-label" 53,86,103,106,116 y con dosis elevadas del fármaco 86 . Una revisión de 13 ensayos clínicos realizados hasta 2005, en indicaciones ajenas a la hemofilia, mostró un 5,3% de eventos adversos en los pacientes que recibían placebo, frente a un 6,0% en los que recibían el tratamiento activo 78 .…”

“…Incluso se ha combinado el fármaco para control de la hemorragia con la trombolisis intratecal, para evitar la obstrucción de los drenajes ventriculares por coágulos 64 . Aunque la población y la etiopatogenia del problema sean diferentes 116 , se ha sugerido el papel profiláctico del aFVIIr en la HIV del neonato prematuro 39,140 ; aunque se necesitan ensayos clínicos que confirmen su eficacia y la ausencia de complicaciones 51,95 .…”

rFVII for Pediatric Acute Intracranial Hemorrhage

“…The hypothesis that early prophylactic administration of rVIIa to extremely preterm infants (Ͻ28 weeks) would reduce the incidence of severe intraventricular hemorrhage needs to be tested. 9 Finally, intracerebral hemorrhage causes severe disability and a staggering economic burden. Because rFVIIa is a very expensive therapy, possible strategies for optimizing its use in these settings in the pediatric population are particularly needed.…”