116 Factor V Mutation Enhances Thrombin Formation in Healthy Newborn Infants

Abstract

Background: At birth, 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 10 pregnant women, with thrombophilia (Factor V Leiden (FVL, n= 7), anticardiolipin antibodies (n= 2), or lupus anticoagulant (n= 1)), treated with low-molecular-weight heparin to improve pregnancy outcome, were enrolled to the study. All pregnancies ended in term vaginal delivery and the infants were born healthy. Blood samples were collected from the umbilical cord, and on postnatal days 1 and 14. Newborns were screened for FVL mutation and 4 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) treated in our neonatal intensive care unit (NICU) was used as an additional control.Results: As expected, enhanced thrombin formation (F1+21.1 nM) was detected in cord blood and on day 1 in all newborns. On day 1, in the 4 newborns with FVL, F1+2 was significantly more elevated (median F1+2= 8.9 nM) than in those negative for FVL (n= 6, median F1+2= 1.8 nM, p= 0.02), or in the 32 newborns in NICU (unknown FVL status) (median F1+2= 2.3 nM, p= 0.007). A significant difference between FVL positive and negative newborns was observed in the pattern of resolution of the thrombin surge; FVL positive infants showed an increase from umbilical sample to day 1 (day 1 minus umbilical cord, median Ä F1+2 = 3.7 nM), whereas F1+2 decreased in FVL negative infants (median Ä F1+2 = −0.7 nM, p= 0.02). By the day 14 F1+2 levels were similar and low in both FVL positive and negative infants.Conclusions: Factor V mutation enhanced thrombin formation in healthy newborns during the first days of life. After two weeks enhanced thrombin formation was normalized.