Role of Hemocoagulase in Pulmonary Hemorrhage in Preterm Infants: A Systematic Review

Pulmonary hemorrhage (PH) in neonates is associated with significant morbidity and mortality. Hemocoagulase is an established hemostatic agent and may be beneficial in neonates with severe PH.This systematic review was performed to investigate the clinical efficacy and safety of hemocoagulase therapy in preterm infants with Pulmonary hemorrhage (PH). The search strategy of the Cochrane Neonatal Review Group was used to determine outcomes following PH in neonates. The primary outcomes were mortality, duration of PH and length of mechanical ventilation. Other morbidities included: Respiratory Distress Syndrome, sepsis, intraventricular hemorrhage, necrotizing enterocolitis and bronchopulmonary dysplasia. The Cochrane Library, MEDLINE, EMBASE and CINAHL and bibliographies of identified trials were searched. The standard methods of the Cochrane Neonatal Review Group and van Tulder’s guidelines were followed independently by the authors to assess study quality, enter data and report outcomes. Typical treatment effects were calculated using fixed confidence intervals (CI). Heterogeneity tests were performed. Two ‘randomized’ controlled studies related to the role of hemocoagulase in neonates were identified: One for treatment of PH and the other for prevention of PH. All preterm infants’ of gestational age ≤ 32 weeks and birth weight ≤ 1500 g with PH were included in the study. A total of 48 and 72 preterm infants were enrolled and randomized into two groups in trial 1 and trial 2 respectively. Mortality risk was significantly lower in the treatment group (RR 0.52; 95%CI 0.31, 0.89, p < 0.02) when hemocoagulase was used as therapy compared to prophylactic use in neonates (RR 0.52; 95%CI 0.26, 1.07, p = 0.07). Duration of PH and mean duration of ventilation were shorter in both treatment and prophylactic groups. Use of hemocoagulase appeared to be effective in preventing PH in premature infants and reduced mortality. However, the potential risks of use of hemocoagulase including adverse effects and the effectiveness of hemocoagulase still remain uncertain due to the lack of good quality large randomized controlled studies. This needs further evaluation, before routine use can be recommended.