Off-label use of recombinant factor VIIa for neonatal pulmonary hemorrhage; a single-center experience

Pulmonary hemorrhage (PH) leads to acute and catastrophic deterioration in neonates, and there is no curative treatment available. Off-label use of recombinant Factor VIIa (rFVIIa) is a promising treatment to control bleeding. The aim of this study was to investigate the efficacy and safety of rFVIIa in neonatal massive PH.

We used rFVIIa for PH in our neonatology unit during October 2022. We compared demographic and prognostic data of neonates with PH, for two years prior to and following this time point. Intravenous rFVIIa (50-90 μg/kg/dose) was administered to patients with life-threatening PH that was unresponsive to conventional therapies including surfactant administration, vitamin K treatment, blood product transfusion, increasing airway pressure, high frequency ventilation, and endotracheal adrenaline. Potential side effects, such as thromboembolism, were monitored for one week.

We present 16 neonates (7 females; 14 preterm) treated with rFVIIa in addition to conventional treatments and compared their clinical outcomes with the rFVIIa-untreated group (n=21). Median (interquartile range [IQR]) birth weight (960 [775-2377] vs 910 [710-1360] g, p=0.20) and gestational age (29 [27-32] vs 27 [27-29] weeks, p=0.25) did not significantly differ between the groups. Median (IQR) postnatal day of PH occurrence was 7.5 (3-15) in the rFVIIa-treated group and 3 (1.5-6) in the rFVIIa-untreated group (p=0.019). Overall, six neonates died of PH complications in the intervention group. All neonates responded to rFVIIa to varying degrees (cessation of bleeding, n=11; reduced bleeding, n=5). A second dose was required in three. No thromboembolism was observed during the treatment period. Death attributable to PH [6 (37%) vs 16 (76%), p=0.042] and overall mortality (7 [43%] vs 18 [86%], p<0.001) were lower and median hospitalization duration (37 [10-95] vs 4 [3-9] days, p=0.001) was longer in the study group than in the control group.

Until proven otherwise by further prospective studies, rFVIIa may be effectively and safely administered at higher doses (90 μg/kg), with repeat dose if necessary, when neonatal life-threatening PH does not respond to conventional treatment.