Factor V Leiden Mutation Enhances Thrombin Formation in Healthy Newborn Infants.

Background: At birth, the coagulation system is activated resulting in thrombin formation in the newborn. In sick newborns, the coagulopathy may lead to bleeding or thrombotic complications. Known genetic prothrombotic defects are risk factors for thrombosis in adults but their potential influence on perinatal coagulopathy remains unknown. Accordingly, we prospectively studied the influence of genetic thrombophilia on thrombin formation during the first two weeks of life.

Methods: Newborns from 22 pregnant women with thrombophilia (Factor V Leiden (FVL), n=16; anticardiolipin antibodies, n= 3; lupus anticoagulant, n=1; protein C deficiency, n=1; prothrombin G20210A mutation, n=1) were enrolled into the study. All women were treated with low-molecular-weight heparin during pregnancy and all the infants were born at term. Blood samples were collected from the umbilical cord, and on postnatal days 1 and 14. Newborns were screened for FVL and prothrombin G20210A mutation. Eight FVL heterozygotes were found. No infant tested positive for anticardiolipin antibodies or lupus anticoagulant. Thrombin formation was assessed by measuring prothrombin fragment F1+2. For samples on day 1, a previous cohort of 32 newborns (mean gestational age 33.6 weeks, unknown FVL status) treated in our neonatal intensive care unit (NICU) was used as an additional control.

Results: Relative to known normal range in adults, enhanced thrombin formation (F1+2>1.1 nM) was detected in cord blood and on day 1 in all newborns followed by near normalization on day 14. The median level of F1+2 from umbilical cord sample to day 1, and to day 14 in FVL negative newborns was 2.4 nM (n=13) − 2.0 nM (n=10) − 2.0 nM (n=12), and in FVL heterozygotes 4.8 nM (n=7) − 5.8 nM (n=5) − 1.7 nM (n=8). In FVL heterozygotes but not in FVL negative newborns the F1+2 decrease from umbilical cord sample to day 14 was significant (Wilcoxon p=0.02). On day 1, the FVL heterozygotes showed elevated F1+2 levels when compared with a cohort of 32 newborns in NICU (median F1+2 2.3 nM in NICU group vs 5.8 nM in FVL heterozygotes; p=0.06).

Conclusions: Factor V heterozygosity was associated with transiently enhanced thrombin formation in healthy newborns during the first days of life.