Thrombin inhibition is impaired in plasma of sick neonates.
The sick neonate may develop spontaneous or catheter-related thromboses, which must in part reflect poor regulation of the formation and activities of the coagulation enzyme, thrombin. We hypothesized that the balance between the generation and inhibition of thrombin may differ in sick neonates compared with healthy neonates. Fifty neonates with respiratory failure requiring mechanical ventilation and 40 healthy neonates were studied on d 1 of life. All neonates had normal coagulation screening tests and a platelet count greater than 150 x 10(9)/L. Plasma pools from neonates with similar gestational age (GA), birth weight, and health status were prepared. Eight plasma pools from 40 healthy neonates of GA 30-38 wk were compared with six plasma pools from 30 sick neonates of GA 30-38 wk. An additional four plasma pools prepared from 20 sick neonates of GA less than 30 wk were studied. Thrombin generation was measured by amidolysis of a chromogenic substrate, S2238, after defibrination, contact activation, and recalcification of the test plasmas. The contributions of antithrombin III, heparin cofactor II, and alpha 2-macroglobulin as inhibitors of 125I-thrombin were quantitated by SDS-PAGE followed by autoradiography and densitometry. Thrombin generation was similar for both healthy and sick neonates of GA 30-38 wk. However, the inhibition of thrombin was impaired in plasma from sick neonates of GA 30-38 wk compared with plasma from healthy neonates of GA 30-38 wk (4.37 +/- 0.22 versus 5.21 +/- 0.21 nmol; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Shah
J K
JK
Department of Pediatrics, McMaster University Medical Centre, Hamilton, Ontario, Canada.
Mitchell
L G
LG
Paes
B
B
Ofosu
F A
FA
Schmidt
B
B
Andrew
M
M
D000990:Antithrombin III / Q000378:metabolism; D015844:Heparin Cofactor II / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000097:blood*; D011516:Prothrombin / Q000378:metabolism; D012127:Respiratory Distress Syndrome, Newborn / Q000097:blood / Q000150:complications; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D013927:Thrombosis / Q000209:etiology; D000511:alpha-Macroglobulins / Q000378:metabolism
D000511:alpha-Macroglobulins; D015844:Heparin Cofactor II; D000990:Antithrombin III; D011516:Prothrombin; D013917:Thrombin