Impaired systemic fibrinolysis in severe neonatal respiratory distress syndrom

ABSTRACT

The intravascular and intra-alveolar deposition of fibrin in severe neonatal respiratory distress syndrome [RDS] have been attributed to activation of clotting. We questioned whether in face of enhanced clotting, fibrinolysis is sufficient in these neonates. Therefore, we aimed to assess plasminogen activator inhibitor-1 [PAI-1] as a marker of fibrinolysis in plasma of neonates with RDS to investigate its relation to disease severity and the possible prognostic value of its early measurement. The study included 65 neonates, all of them were clinically assessed within 6 hours of birth for inclusion in the study. The study group consisted of 45 preterm neonates, 30 with RDS, and 15 healthy preterm control neonates. The remaining twenty neonates were fullterms; 10 had clinical evidence of infection and 10 were healthy fullterm control neonates. Neonates with RDS were clinically and radiologically evaluated to assign severity and accordingly they were categorized into a severe group and a mild to moderate group. Blood samples were obtained from these neonates while on mechanical ventilation during the first day of life. Fraction of inspiratory oxygen [FiO2] was determined and they were clinically followed up throughout the whole duration of ventilation. Laboratory investigations included CBC, C-reactive protein [CRP], ABG and plasma PAI-1 determination for all neonates as well as a coagulation assay including PT, PTT, fibrinogen and fibrin degradation products [FDPS] done for 18 RDS neonates. Mean plasma concentrations of PAI-1 were significantly elevated in PT neonates with RDS as a whole [P<0.001] and in each subgroup [P<0.01] as compared to control PT neonates. Severe RDS group showed significantly higher PAI-1 in plasma as compared to the mild to moderate group [P<0.001]. A significant positive correlation existed between PAI-1 and FiO2 in all neonates with RDS [P<0.01]. Fibrinogen levels were significantly lower in neonates with severe RDS as compared to the mild to moderate group [P<0.05] and they were negatively correlated to plasma PAI-1 in all studied RDS neonates [P<0.05]. The ratio of FDPs between 5 and 20 to FDPs<5 was 91 in the mild to moderate RDS group, compared to 11 in the severe group. Plasma levels of PAI-1 in full term neonates with systemic infection were significantly higher as compared to healthy fullterms [P<0.05]. Sepsis was documented in 21.05% of deaths among neonates with RDS. Retrospective tracing of CRP in neonates with RDS who died revealed values that were non-significantly higher than those of survivors [P>0.05]. Meanwhile, Plasma PAI-1 levels in deceased were significantly higher than those of survivors [P<0.001]. PAI-1 cut off value of 58 ng/ml was 60% sensitive and 73.68% specific to predict mortality in RDS. In severe RDS, high PAI-1 impairs systemic fibrinolysis which likely facilitates the deleterious effects of early clotting activation, contributing to disease severity and mortality. Plasma level of PAI-1 within 24 hours of birth, though might be influenced by early infection may be a useful predictor of outcome in neonatal RDS