title: Increased tissue-type plasminogen activator antigen release is not accompanied by increased systemic fibrinolytic activity in severe neonatal respiratory distress syndrome.
abstract: Intravascular and intraalveolar fibrin depositions in preterm infants with severe respiratory distress syndrome (RDS) have been attributed to activation of clotting. We questioned whether in the face of activated clotting, fibrinolysis is sufficient in these infants. We found, in infants with severe RDS within 6 to 12 h of birth, increased median thrombin-antithrombin III complex formation (11.1 versus 1.3 ng/mL in the group with mild-to-moderate RDS, p < 0.001), indicating activation of clotting. Simultaneously, we found increased tissue-type plasminogen activator antigen (t-PA) release in plasma of these infants represented by increased median t-PA plasma concentrations (8.3 versus 2.5 ng/mL in the group with mild-to-moderate RDS, p < 0.01). This increased t-PA release was not accompanied with more plasminogen and antiplasmin consumption and with more fibrin and fibrinogen degradation than in the infants with mild-to-moderate RDS because plasma plasminogen and antiplasmin activity and total fibrin and fibrinogen degradation product concentrations were similar in both groups. We have found that activated clotting and t-PA plasma concentrations are positively correlated with arterial-to-alveolar oxygen tension ratio and ventilator efficiency index values. Plasminogen and antiplasmin activity, and total fibrin and fibrinogen degradation product concentrations were not correlated with these continuous measures of RDS severity. In neonatal RDS, clotting activity contributes to disease severity. Insufficient fibrinolysis likely facilitates the deleterious effects of activated clotting.
authors: Beatrix Childrens Hospital, Division of Neonatology, University of Groningen, The Netherlands.
authors: F
authors: F
authors: Brus
authors: S B
authors: SB
authors: Oetomo
authors: J
authors: J
authors: Schieving
authors: E
authors: E
authors: Groothuis
authors: A
authors: A
authors: Okken
authors: W
authors: W
authors: van Oeveren
mesh_terms: D000990:Antithrombin III / Q000378:metabolism*; D001034:Apgar Score; D002543:Cerebral Hemorrhage / Q000097:blood / Q000209:etiology / Q000503:physiopathology; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005341:Fibrinolysin / Q000378:metabolism; D005342:Fibrinolysis; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D010100:Oxygen / Q000032:analysis / Q000097:blood; D010313:Partial Pressure; D010447:Peptide Hydrolases / Q000378:metabolism*; D010958:Plasminogen / Q000378:metabolism; D010976:Platelet Count; D012127:Respiratory Distress Syndrome, Newborn / Q000097:blood* / Q000503:physiopathology*; D010959:Tissue Plasminogen Activator / Q000097:blood* / Q000378:metabolism
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; C046193:antithrombin III-protease complex; D000990:Antithrombin III; D010958:Plasminogen; D010447:Peptide Hydrolases; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D010100:Oxygen