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Plasma proteomics of patients with non-valvular atrial fibrillation on chronic anti-coagulation with warfarin or a direct factor Xa inhibitor.

Publication ,  Journal Article
Chan, MY; Lin, M; Lucas, J; Moseley, A; Thompson, JW; Cyr, D; Ueda, H; Kajikawa, M; Ortel, TL; Becker, RC
Published in: Thromb Haemost
December 2012

Plasma proteins mediate thrombogenesis, inflammation, endocardial injury and structural remodelling in atrial fibrillation (AF). We hypothesised that anti-coagulation with rivaroxaban, a direct factor Xa inhibitor, would differentially modulate biologically-relevant plasma proteins, compared with warfarin, a multi-coagulation protein antagonist. We performed unbiased liquid chromatography/tandem mass spectroscopy and candidate multiplexed protein immunoassays among Japanese subjects with non-valvular chronic AF who were randomly assigned to treatment with 24 weeks of rivaroxaban (n=93) or warfarin (n=94). Nine metaproteins, including fibulin-1 (p=0.0033), vitronectin (p=0.0010), haemoglobin α (p=0.0012), apolipoproteins C-II (p=0.0017) and H (p=0.0023), complement C5 precursor (p=0.0026), coagulation factor XIIIA (p=0.0026) and XIIIB (p=0.0032) subunits, and 10 candidate proteins, including thrombomodulin (p=0.0004), intercellular adhesion molecule-3 (p=0.0064), interleukin-8 (p=0.0007) and matrix metalloproteinase-3 (p=0.0003), were differentially expressed among patients with and without known clinical risk factors for stroke and bleeding in AF. Compared with warfarin, rivaroxaban treatment was associated with a greater increase in thrombomodulin (Δ 0.1 vs. 0.3 pg/ml, p=0.0026) and a trend towards a reduction in matrix metalloproteinase-9 (Δ 2.2 vs. -4.9 pg/ml, p=0.0757) over 24 weeks. Only modest correlations were observed between protein levels and prothrombin time, factor Xa activity and prothrombinase-induced clotting time. Plasma proteomics can identify distinct functional patterns of protein expression that report on known stroke and bleeding risk phenotypes in an ethnically-homogeneous AF population. The greater upregulation of thrombomodulin among patients randomised to rivaroxaban represents a proof-of-principle that pharmacoproteomics can be employed to discern novel effects of factor Xa inhibition beyond standard pharmacodynamic measures.

Duke Scholars

Published In

Thromb Haemost

DOI

EISSN

2567-689X

Publication Date

December 2012

Volume

108

Issue

6

Start / End Page

1180 / 1191

Location

Germany

Related Subject Headings

  • Warfarin
  • Thrombosis
  • Thiophenes
  • Stroke
  • Rivaroxaban
  • Risk Factors
  • Proteomics
  • Morpholines
  • Male
  • Humans
 

Citation

APA
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ICMJE
MLA
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Chan, M. Y., Lin, M., Lucas, J., Moseley, A., Thompson, J. W., Cyr, D., … Becker, R. C. (2012). Plasma proteomics of patients with non-valvular atrial fibrillation on chronic anti-coagulation with warfarin or a direct factor Xa inhibitor. Thromb Haemost, 108(6), 1180–1191. https://doi.org/10.1160/TH12-05-0310
Chan, Mark Y., Min Lin, Joseph Lucas, Arthur Moseley, J Will Thompson, Derek Cyr, Hitoshi Ueda, Mariko Kajikawa, Thomas L. Ortel, and Richard C. Becker. “Plasma proteomics of patients with non-valvular atrial fibrillation on chronic anti-coagulation with warfarin or a direct factor Xa inhibitor.Thromb Haemost 108, no. 6 (December 2012): 1180–91. https://doi.org/10.1160/TH12-05-0310.
Chan MY, Lin M, Lucas J, Moseley A, Thompson JW, Cyr D, et al. Plasma proteomics of patients with non-valvular atrial fibrillation on chronic anti-coagulation with warfarin or a direct factor Xa inhibitor. Thromb Haemost. 2012 Dec;108(6):1180–91.
Chan, Mark Y., et al. “Plasma proteomics of patients with non-valvular atrial fibrillation on chronic anti-coagulation with warfarin or a direct factor Xa inhibitor.Thromb Haemost, vol. 108, no. 6, Dec. 2012, pp. 1180–91. Pubmed, doi:10.1160/TH12-05-0310.
Chan MY, Lin M, Lucas J, Moseley A, Thompson JW, Cyr D, Ueda H, Kajikawa M, Ortel TL, Becker RC. Plasma proteomics of patients with non-valvular atrial fibrillation on chronic anti-coagulation with warfarin or a direct factor Xa inhibitor. Thromb Haemost. 2012 Dec;108(6):1180–1191.
Journal cover image

Published In

Thromb Haemost

DOI

EISSN

2567-689X

Publication Date

December 2012

Volume

108

Issue

6

Start / End Page

1180 / 1191

Location

Germany

Related Subject Headings

  • Warfarin
  • Thrombosis
  • Thiophenes
  • Stroke
  • Rivaroxaban
  • Risk Factors
  • Proteomics
  • Morpholines
  • Male
  • Humans