The procoagulant effects of factor V Leiden may be balanced against decreased levels of factor V and do not reflect in vivo thrombin formation in newborns.
Thrombin regulation in newborns remains incompletely understood. We studied tissue factor-initiated thrombin formation in cord plasma in vitro, and the effects of Factor V(Leiden) (FVL) heterozygosity on thrombin regulation both in vitro and in vivo in newborns. Pregnant women with known thrombophilia (n=27) were enrolled in the study. Cord blood and venous blood at the age of 14 days were collected from 11 FVL heterozygous newborns (FVL-positive) and from 16 FVL-negative newborns. Prothrombin fragment F1 +2 and coagulation factors were measured. Tissue factor-initiated thrombin formation was studied in cord platelet-poor plasma (PPP) of FVL-negative and -positive newborns, and in both PPP and platelet-rich plasma (PRP) of healthy controls. The endogenous thrombin potential (ETP) in cord PPP or PRP was approximately 60% of that in adult plasma, while thrombin formation started approximately 55% and approximately 40% earlier in cord PPP and PRP, respectively. Further, in FVL-positive newborns thrombin formation started significantly earlier than in FVL-negative newborns. Exogenous activated protein C (APC) decreased ETP significantly more in cord than in adult PRP. In FVL-negative cord plasma 5 nM 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 +2 but significantly decreased levels of factorV compared with FVL-negative newborns 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 (FV 1.15+/-0.04 U/ml vs. 1.32+/- 0.05 U/ml, p=0.03). In conclusion, newborn plasma showed more rapid thrombin formation and enhanced sensitivity to APC compared with adult plasma. FVL conveyed APC resistance 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 be the observed lower level of factor V in FVL heterozygous newborns.
Hyytiäinen
Satu
S
Hospital for Children and Adolescents, Helsinki, Finland.
Wartiovaara-Kautto
Ulla
U
Ulander
Veli-Matti
VM
Kaaja
Risto
R
Heikinheimo
Markku
M
Petäjä
Jari
J
D001777:Blood Coagulation; D005165:Factor V / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006579:Heterozygote; D006801:Humans; D066298:In Vitro Techniques; D007231:Infant, Newborn; D008297:Male; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000097:blood* / Q000235:genetics; D011486:Protein C / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism*; D019851:Thrombophilia / Q000097:blood* / Q000235:genetics; D013997:Time Factors
D011486:Protein C; C095381:factor V Leiden; D005165:Factor V; D013917:Thrombin