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Arterioscler Thromb Vasc Biol. 2009 Nov;29(11):1968-74. doi: 10.1161/ATVBAHA.109.191551. Epub 2009 Aug 20.

FVII, FVIIa, and downstream markers of extrinsic pathway activation differ by EPCR Ser219Gly variant in healthy men.

Author information

1
Centre for Cardiovascular Genetics, Division of Medicine, University College London, UK. h.ireland@ucl.ac.uk

Abstract

OBJECTIVE:

The purpose of this study was to determine the effect of a variant in EPCR (Ser219Gly), previously shown to affect EPCR shedding, on plasma FVII, FVIIa, and downstream markers of activated coagulation.

METHODS AND RESULTS:

Statistical analysis was undertaken in approximately 2000 healthy middle aged men (NPHSII). Higher soluble EPCR levels were confirmed for Gly allele carriers (P<0.0001). Significantly higher levels of FVII, FVIIa, and downstream markers of activated coagulation in the extrinsic pathway (FIX activation pep [FIXpep]; FX activation pep [FXpep]), and prothrombin F1+2 (F1+2) were identified in baseline samples, in Gly carriers compared to Ser/Ser (P<or=0.04 for trend). In repeat samples collected for up to 5 years, levels of FVII and F1+2 were higher in Gly allele carriers compared to Ser/Ser by (FVII: 6.9% CI 5.5 to 8.4 in Ser/Gly; and 23.4% CI 16.3 to 30.8 in Gly/Gly, P<0.0001), (F1+2: 8.1% CI 5.2 to 11.1 in Ser/Gly; 25.2% CI 11.8 to 40.3 in Gly/Gly, P<0.04), confirming reproducibility of findings at baseline. Molar ratios for FIXpep, FXpep, and F1+2 to FVIIa were constant in Ser/Ser and Ser/Gly but tended to be higher in Gly/Gly, reaching statistical significance for FIXpep:FVIIa (P=0.04).

CONCLUSIONS:

These data suggest that higher levels of FVII and FVIIa circulate when EPCR shedding is greatest. Furthermore, these results suggest consequences for activation of extrinsic coagulation.

PMID:
19696402
PMCID:
PMC2775706
DOI:
10.1161/ATVBAHA.109.191551
[Indexed for MEDLINE]
Free PMC Article

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