Elevated factor VII as a risk factor for recurrent fetal loss Relationship to factor VII gene polymorphisms
Connie H. Miller1 , Christine De Staercke 1 , Jane Benson1 , W. Craig Hooper 1 , Anne Dilley 1*, Bruce L. Evatt1 , Carlos Benito 2 , Anne Patterson-Barnett3 , Daniel Eller 3 , Claire S. Philipp4
1 Division of Hereditary Blood Disorders, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia, USA 2 Division of Maternal-Fetal Medicine, St. Peter’s University Hospital, New Brun
Summary Haemostatic abnormalities can be detected in a portion of thewomen who have recurrent fetal loss.We measured factor VIIcoagulant activity (FVII:C) in 65 women with 3 or more fetallosses (recurrent cases), 31 women with one 2nd or 3rd trimesterloss (late loss cases), and 81 women with only live births(controls). FVII:C was greater than 2 standard deviations abovethe mean for controls in 9 recurrent cases (13.8%) and 2 controls(2.5%) for an odds ratio of 6.35 (95% CI 1.32–30.52,p=0.012). In recurrent cases, mean levels were significantlyhigher than controls for FVII:C (p=0.003), FVII antigen(p=0.024), and FVIIa (p=0.001). Late loss cases had an odds ratioof 4.23 (95% CI 0.67–26.67, p=0.098) with FVII:C, FVII antigen,and FVIIa not significantly different from the controls. DNA was examined for the presence of mutations or polymorphisms inthe promoter region of the FVII gene, using denaturing HPLC.Abnormal patterns were confirmed with direct sequencing. Apreviously reported polymorphism, –402 G>A, was found to bepresent in 11/14 subjects with elevated FVII:C (79%) and 43% ofthose with normal levels (p=0.029).FVII:C,FVII antigen and FVIIavaried significantly with genotype; however, genotype frequenciesdid not differ between controls and either case group. Noother promoter polymorphisms were identified.This is the firstreport of a significant elevation of FVII in a population with recurrentfetal loss.These data suggest the need for further investigationof this potential risk factor.