Evidence of in vivo generation of thrombin in patients with small-for-gestational-age fetuses and pre-eclampsia

Abstract

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 objectiveof this study was to determine whether there was evidence of in vivo generation of thrombin, the ratelimiting 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 weredetermined with a specific and sensitive immunoassay. Statistical analysis was performed with non-parametric statistics.Results: The median plasma TAT complex concentrations were significantlyhigher in patients who delivered SGA neonates than in normal pregnant women (SGA, median 24.2 μg/l; range 11.9-788.7 vs. normal pregnancy, median: 14.4 μg/l; range 6.8-26.9; p = 0.001). Patientswith pre-eclampsia had a higher median plasma TAT complex concentration than normal pregnant women (pre-eclampsia, median 18.1 μg/l; range 10.0-75.2 vs. normal pregnancy, median 14.4 μg/l; range 6.8-26.9;p = 0.02).Conclusion: In vivo generation of thrombin, determined by the plasma concentrations of TAT complexes, is higher in patients with SGA fetuses and patients with pre-eclampsiathan in normal pregnancy.