Elevated factor VII as a risk factor for recurrent fetal loss: Relationship to factor VII gene polymorphisms

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

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1089-1094
Number of pages6
JournalThrombosis and Haemostasis
Volume93
Issue number6
DOIs
StatePublished - Jun 1 2005
Externally publishedYes

Fingerprint

Factor VII
Genes
Antigens
Odds Ratio
Genotype
Live Birth
Hemostatics
Contraception
Genetic Promoter Regions
factor VII clotting antigen
High Pressure Liquid Chromatography
Mutation
DNA
Population

All Science Journal Classification (ASJC) codes

  • Hematology

Cite this

Miller, C. H., De Staercke, C., Benson, J., Hooper, W. C., Dilley, A., Evatt, B. L., ... Philipp, C. S. (2005). Elevated factor VII as a risk factor for recurrent fetal loss: Relationship to factor VII gene polymorphisms. Thrombosis and Haemostasis, 93(6), 1089-1094. https://doi.org/10.1160/TH04-09-0583
Miller, Connie H. ; De Staercke, Christine ; Benson, Jane ; Hooper, W. Craig ; Dilley, Anne ; Evatt, Bruce L. ; Benito, Carlos ; Patterson-Barnett, Anne ; Eller, Daniel ; Philipp, Claire S. / Elevated factor VII as a risk factor for recurrent fetal loss : Relationship to factor VII gene polymorphisms. In: Thrombosis and Haemostasis. 2005 ; Vol. 93, No. 6. pp. 1089-1094.
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Miller, CH, De Staercke, C, Benson, J, Hooper, WC, Dilley, A, Evatt, BL, Benito, C, Patterson-Barnett, A, Eller, D & Philipp, CS 2005, 'Elevated factor VII as a risk factor for recurrent fetal loss: Relationship to factor VII gene polymorphisms', Thrombosis and Haemostasis, vol. 93, no. 6, pp. 1089-1094. https://doi.org/10.1160/TH04-09-0583

Elevated factor VII as a risk factor for recurrent fetal loss : Relationship to factor VII gene polymorphisms. / Miller, Connie H.; De Staercke, Christine; Benson, Jane; Hooper, W. Craig; Dilley, Anne; Evatt, Bruce L.; Benito, Carlos; Patterson-Barnett, Anne; Eller, Daniel; Philipp, Claire S.

In: Thrombosis and Haemostasis, Vol. 93, No. 6, 01.06.2005, p. 1089-1094.

Research output: Contribution to journalArticle

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T1 - Elevated factor VII as a risk factor for recurrent fetal loss

T2 - Relationship to factor VII gene polymorphisms

AU - Miller, Connie H.

AU - De Staercke, Christine

AU - Benson, Jane

AU - Hooper, W. Craig

AU - Dilley, Anne

AU - Evatt, Bruce L.

AU - Benito, Carlos

AU - Patterson-Barnett, Anne

AU - Eller, Daniel

AU - Philipp, Claire S.

PY - 2005/6/1

Y1 - 2005/6/1

N2 - 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.

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