Thrombin/antithrombin III complex formation in the neonatal respiratory distress syndrome

Intravascular and intra-alveolar thrombin generation may exacerbate the pulmonary hypertension and surfactant dysfunction that characterize the neonatal respiratory distress syndrome (RDS). Although low levels of the most important thrombin inhibitor, antithrombin III (AT III), have been reported in infants with RDS, direct evidence of increased intravascular thrombin generation has been lacking. Accordingly, the objective of this study was to determine whether thrombin generation is increased in severe neonatal RDS. Thirty-nine infants of 25 to 29 wk gestation with a clinical and radiologic diagnosis of RDS were enrolled in a prospective cohort study. Plasma levels of thrombin/antithrombin III complexes (TAT) and AT III activity, measured 36 to 72 h after birth, were related to RDS severity. Seventeen infants had severe RDS (mean airway pressure greater than 10 cm H2O or FlO2 greater than 0.8), and 22 had mild or moderate disease. Mean birthweight (1,017 versus 1,054 g) and mean gestational age (27.8 versus 27.4 wk) were similar in both groups. The median TAT level in infants with severe RDS was significantly higher than that in patients with mild or moderate disease (10.7 and 4.0 micrograms/L, respectively; p less than 0.001). In addition, the mean AT III activity in infants with severe RDS was significantly lower than that in less severely affected patients (0.31 and 0.46 U/ml, respectively; p less than 0.01). Considering the entire cohort, plasma TAT levels were inversely correlated with the arterial/alveolar oxygen tension ratio (r = -0.48, p = 0.0022) and the ventilator efficiency index (r = -0.51, p = 0.0011). The elevated TAT levels and reduced AT III activity in infants with severe RDS are consistent with increased thrombin generation and resulting AT III consumption. Therefore, to regulate thrombin activity, these infants may benefit from replacement therapy with AT III concentrate.