Elevated factor VII as a risk factor for recurrent fetal loss

Connie H. Miller; Christine De Staercke; Jane Benson; Craig W. Hooper; Anne Dilley; Bruce L. Evatt; Carlos Benito; Anne Patterson-Barnett; Daniel Eller; Claire S. Philipp

doi:10.1160/TH04-09-0583

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2005; 93(06): 1089-1094
DOI: 10.1160/TH04-09-0583

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Elevated factor VII as a risk factor for recurrent fetal loss

Relationship to factor VII gene polymorphisms

Authors

Connie H. Miller

¹Division of Hereditary Blood Disorders, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
Christine De Staercke

¹Division of Hereditary Blood Disorders, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
Jane Benson

¹Division of Hereditary Blood Disorders, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
Craig W. Hooper

¹Division of Hereditary Blood Disorders, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
Anne Dilley^*

¹Division of Hereditary Blood Disorders, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
Bruce L. Evatt

¹Division of Hereditary Blood Disorders, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
Carlos Benito

²Division of Maternal-Fetal Medicine, St. Peter’s University Hospital, New Brunswick, New Jersey, USA
Anne Patterson-Barnett

³Northside Women’s Specialists, Atlanta, Georgia, USA
Daniel Eller

³Northside Women’s Specialists, Atlanta, Georgia, USA
Claire S. Philipp

⁴Division of Hematology, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA

Abstract

Summary

Haemostatic abnormalities can be detected in a portion of the women who have recurrent fetal loss. We measured factor VII coagulant activity (FVII:C) in 65 women with 3 or more fetal losses (recurrent cases), 31 women with one 2nd or 3rd trimester loss (late loss cases), and 81 women with only live births (controls). FVII:C was greater than 2 standard deviations above the 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 significantly higher than controls for FVII:C (p=0.003), FVII antigen (p=0.024), and FVIIa (p=0.001). Late loss cases had an odds ratio of 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 in the promoter region of the FVII gene, using denaturing HPLC. Abnormal patterns were confirmed with direct sequencing. A previously reported polymorphism,–402 G>A, was found to be present in 11/14 subjects with elevated FVII:C (79%) and 43% of those with normal levels (p=0.029). FVII:C, FVII antigen and FVIIa varied significantly with genotype; however, genotype frequencies did not differ between controls and either case group. No other promoter polymorphisms were identified. This is the first report of a significant elevation of FVII in a population with recurrent fetal loss. These data suggest the need for further investigation of this potential risk factor.

Keywords

Factor VII - factor VII polymorphisms - fetal loss - recurrent fetal loss

Full Text

References

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