Summary

Thrombin regulation in newborns remains incompletely understood.We studied tissue factor-initiated thrombin formation incord plasma in vitro , and the effects of Factor V_Leiden (FVL) heterozygosityon thrombin regulation both in vitro and in vivo innewborns. Pregnant women with known thrombophilia (n=27)were enrolled in the study. Cord blood and venous blood at theage of 14 days were collected from 11 FVL heterozygous newborns(FVL-positive) and from 16 FVL-negative newborns. Prothrombinfragment F1+2 and coagulation factors weremeasured. Tissue factor-initiated thrombin formation wasstudied in cord platelet-poor plasma (PPP) of FVL-negative and-positive newborns, and in both PPP and platelet-rich plasma newborns.Exogenous activated protein C (APC) decreased ETPsignificantly more in cord than in adult PRP. In FVL-negative cordplasma 5nM APC decreased ETP by 17.4±3.5% (mean±SEM)compared with only 3.5±3.8% in FVL-positive cord plasma(p=0.01). FVL-positive newborns showed similar levels of F1+2but significantly decreased levels of factorV compared with FVLnegativenewborns both in cord plasma (FV 0.82±0.07 U/ml vs.0.98±0.05 U/ml, p=0.03) and at the age of two weeks (FV1.15±0.04 U/ml vs. 1.32±0.05 U/ml, p=0.03). In conclusion, newbornplasma showed more rapid thrombin formation and enhancedsensitivity toAPC compared with adult plasma.FVL conveyedAPCresistance and a procoagulant effect in newborn plasma.Lack of elevated F1+2 levels in FVL-positive infants,however,suggested the existence of balancing mechanisms; one could bethe observed lower level of factor V in FVL heterozygous ne(PRP) of healthy controls.The endogenous thrombin potential(ETP) in cord PPP or PRP was ~ 60% of that in adult plasma,whilethrombin formation started ~ 55% and ~ 40% earlier in cord PPPand PRP, respectively. Further, in FVL-positive newborns thrombinformation started significantly earlier than in FVL-n