Thrombin inhibition by fetal distal lung epithelium is different in fetal and adult plasma.
Intra-alveolar fibrin deposition is a cardinal feature of neonatal respiratory distress syndrome and likely contributes to short-term and long-term morbidity. Previous studies have shown that fetal distal lung epithelial cell (FDLE) surfaces express procoagulant activity when incubated with adult plasma and may therefore provide one mechanism by which fibrin is generated. However, plasma concentrations of prothrombin and thrombin inhibitors differ significantly at birth and during the first weeks of life compared with adult values. Therefore, we measured thrombin-generating capacity and inhibitor complex formation in cord and adult plasma incubated in the presence of FDLE. Although starting cord plasma concentrations of prothrombin were 43% of adult values, the amount of thrombin generated was decreased by only 21%. When cord plasma concentrations of prothrombin were selectively increased to adult values, the amount of thrombin generated surpassed adult plasma by 89%. The latter observations suggested that thrombin inhibition was impaired in cord plasma compared with adult plasma and supplementation of cord plasma with antithrombin III (ATIII) as well as prothrombin returned thrombin generation to adult levels. However, the percentage of thrombin complexed to inhibitors (59%) at the completion of the experiments was similar in cord, cord plus prothrombin, cord plus prothrombin plus ATIII, and adult plasmas. Although a higher proportion of thrombin was inhibited by alpha 2-macroglobulin (alpha 2M) in cord plasma and cord plasma plus prothrombin, this did not compensate for the decreased amount of thrombin inhibited by ATIII. When cord plasma was supplemented with ATIII as well as prothrombin, the proportions of thrombin complexed by the different inhibitors were similar to those of adult plasma.(ABSTRACT TRUNCATED AT 250 WORDS)
Andrew
M
M
Department of Pediatrics, University of Toronto, Hospital for Sick Children's Research Institute, Ontario, Canada.
Berry
L
L
O'Brodovich
H
H
D000818:Animals; D000990:Antithrombin III / Q000378:metabolism / Q000494:pharmacology; D002478:Cells, Cultured; D004848:Epithelium / Q000196:embryology / Q000502:physiology; D005312:Fetal Blood / Q000378:metabolism*; D005337:Fibrin / Q000378:metabolism; D007700:Kinetics; D008168:Lung / Q000196:embryology* / Q000502:physiology; D011516:Prothrombin / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000511:alpha-Macroglobulins / Q000378:metabolism / Q000494:pharmacology
D000511:alpha-Macroglobulins; D000990:Antithrombin III; D011516:Prothrombin; D005337:Fibrin; D013917:Thrombin