Evidence of in vivo generation of thrombin in patients with small-for-gestational-age fetuses and pre-eclampsia.
OBJECTIVE
Thrombotic lesions in the maternal or fetal compartments are frequently observed in the placentas of patients with small-for-gestational-age (SGA) fetuses and in pre-eclampsia. The objective of this study was to determine whether there was evidence of in vivo generation of thrombin, the rate-limiting enzyme responsible for the formation of fibrin. The plasma concentrations of thrombin-antithrombin (TAT) complexes were used as an index of thrombin generation.


METHODS
TAT complexes were measured in the plasma from 68 women from the following groups: normal pregnancy (n = 29); pre-eclampsia (n = 26); and SGA (defined as estimated fetal weight below the 10th centile for gestational age, which was confirmed by neonatal birth weight) (n = 13). TAT complex plasma concentrations were determined with a specific and sensitive immunoassay. Statistical analysis was performed with non-parametric statistics.


RESULTS
The median plasma TAT complex concentrations were significantly higher in patients who delivered SGA neonates than in normal pregnant women (SGA, median 24.2 microg/l; range 11.9-788.7 vs. normal pregnancy, median: 14.4 microg/l; range 6.8-26.9; p = 0.001). Patients with pre-eclampsia had a higher median plasma TAT complex concentration than normal pregnant women (pre-eclampsia, median 18.1 microg/l; range 10.0-75.2 vs. normal pregnancy, median 14.4 microg/l; range 6.8-26.9; p = 0.02).


CONCLUSIONS
In vivo generation of thrombin, determined by the plasma concentrations of TAT complexes, is higher in patients with SGA fetuses and patients with pre-eclampsia than in normal pregnancy.
Chaiworapongsa
T
T
Perinatology Research Branch, NICHD, Bethesda, Maryland, USA.
Yoshimatsu
J
J
Espinoza
J
J
Kim
Y M
YM
Berman
S
S
Edwin
S
S
Yoon
B H
BH
Romero
R
R
D000293:Adolescent; D000328:Adult; D000990:Antithrombin III / Q000096:biosynthesis*; D003430:Cross-Sectional Studies; D005260:Female; D005315:Fetal Diseases / Q000097:blood* / Q000209:etiology; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D010447:Peptide Hydrolases / Q000096:biosynthesis* / Q000097:blood; D011225:Pre-Eclampsia / Q000097:blood* / Q000209:etiology; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000097:blood* / Q000209:etiology; D013917:Thrombin / Q000032:analysis / Q000096:biosynthesis*; D013927:Thrombosis / Q000097:blood* / Q000209:etiology
C046193:antithrombin III-protease complex; D000990:Antithrombin III; D010447:Peptide Hydrolases; D013917:Thrombin