Display options
Cite
Cushman M, Larson JC, Rosendaal FR, et al. Biomarkers, menopausal hormone therapy and risk of venous thrombosis: The Women's Health Initiative. Res Pract Thromb Haemost. 2018;2(2):310-319doi: 10.1002/rth2.12100.
Cushman, M., Larson, J. C., Rosendaal, F. R., Heckbert, S. R., Curb, J. D., Phillips, L. S., Baird, A. E., Eaton, C. B., & Stafford, R. S. (2018). Biomarkers, menopausal hormone therapy and risk of venous thrombosis: The Women's Health Initiative. Research and practice in thrombosis and haemostasis, 2(2), 310-319. https://doi.org/10.1002/rth2.12100
Cushman, Mary, et al. "Biomarkers, menopausal hormone therapy and risk of venous thrombosis: The Women's Health Initiative." Research and practice in thrombosis and haemostasis vol. 2,2 (2018): 310-319. doi: https://doi.org/10.1002/rth2.12100
Cushman M, Larson JC, Rosendaal FR, Heckbert SR, Curb JD, Phillips LS, Baird AE, Eaton CB, Stafford RS. Biomarkers, menopausal hormone therapy and risk of venous thrombosis: The Women's Health Initiative. Res Pract Thromb Haemost. 2018 Apr 17;2(2):310-319. doi: 10.1002/rth2.12100. eCollection 2018 Apr. PMID: 30046733; PMCID: PMC5974918.
Copy Download .nbib Format: NLM
Share it on

Res Pract Thromb Haemost. 2018 Apr 17;2(2):310-319. doi: 10.1002/rth2.12100. eCollection 2018 Apr.

Biomarkers, menopausal hormone therapy and risk of venous thrombosis: The Women's Health Initiative.

Research and practice in thrombosis and haemostasis

Mary Cushman, Joseph C Larson, Frits R Rosendaal, Susan R Heckbert, J David Curb, Lawrence S Phillips, Alison E Baird, Charles B Eaton, Randall S Stafford

Affiliations

  1. Department of Medicine Larner College of Medicine University of Vermont Burlington VT USA.
  2. Public Health Sciences Division Fred Hutchinson Cancer Research Center Seattle WA USA.
  3. Department of Clinical Epidemiology Leiden University Medical Center Leiden the Netherlands.
  4. Department of Epidemiology Cardiovascular Health Research Unit University of Washington Seattle WA USA.
  5. Department of Geriatric Medicine University of Hawaii Honolulu HI USA.
  6. Atlanta VA Medical Center Decatur GA USA.
  7. Division of Endocrinology and Metabolism Emory University School of Medicine Atlanta GA USA.
  8. Department of Neurology State University of New York Downstate Medical Center Brooklyn NY USA.
  9. Department of Family Medicine Alpert Medical School Brown University Providence RI USA.
  10. Department of Epidemiology School of Public Health Brown University Providence RI USA.
  11. Program on Prevention Outcomes and Practices Stanford Prevention Research Center Stanford University Palo Alto CA USA.

PMID: 30046733 PMCID: PMC5974918 DOI: 10.1002/rth2.12100

Abstract

BACKGROUND: Oral menopausal hormone therapy causes venous thrombosis but whether biomarkers of thrombosis risk can identify women at risk is unknown.

METHODS: We completed a nested case control study in the two Women's Health Initiative hormone trials; 27 347 women aged 50-79 were randomized to hormone therapy (conjugated equine estrogen with or without medroxyprogesterone acetate) or placebo. With 4 years follow-up, biomarkers were measured using stored baseline samples prior to starting treatment, and one-year later, in 215 women who developed thrombosis and 867 controls.

RESULTS: Overall, lower protein C and free protein S, and higher D-dimer, prothrombin fragment 1.2 and plasmin-antiplasmin complex were associated with risk of future thrombosis with odds ratios ranging from 1.9 to 3.2. Compared to women with normal biomarkers assigned to placebo, the risk of thrombosis with hormone therapy was increased among women with abnormal biomarkers, especially elevated D-dimer, elevated plasmin-antiplasmin, and low free protein S; the largest association was for D-dimer: odds ratio 6.0 (95% CI 3.6-9.8). Differences in associations by hormone use were not significant on the multiplicative scale. Considering a multi-marker score of eight biomarkers, women with three or more abnormal biomarkers had 15.5-fold increased odds of VT (95% CI 6.8-35.1). One-year changes in biomarkers were not robustly associated with subsequent thrombosis risk.

CONCLUSION: Abnormal levels of biomarkers of thrombosis risk identified women at increased risk of future venous thrombosis with oral menopausal hormone therapy. Findings support the potential for clinical use of D-dimer testing in advance of hormone therapy prescription.

Keywords: D‐dimer; blood coagulation; menopausal hormone therapy; risk assessment; risk factor; venous thromboembolism; venous thrombosis

References

  1. JAMA Intern Med. 2014 Jan;174(1):25-31 - PubMed
  2. Thromb Haemost. 2000 Jan;83(1):29-34 - PubMed
  3. Ann Epidemiol. 2003 Oct;13(9 Suppl):S122-8 - PubMed
  4. PLoS Clin Trials. 2007 Jun 15;2(6):e28 - PubMed
  5. Semin Hematol. 2007 Apr;44(2):62-9 - PubMed
  6. Thromb Haemost. 2002 Apr;87(4):614-21 - PubMed
  7. Blood. 2003 Feb 15;101(4):1243-8 - PubMed
  8. Blood. 2009 Oct 1;114(14):2878-83 - PubMed
  9. Blood. 2000 Jun 15;95(12):3678-82 - PubMed
  10. Control Clin Trials. 1998 Feb;19(1):61-109 - PubMed
  11. Arterioscler Thromb Vasc Biol. 1999 Mar;19(3):493-8 - PubMed
  12. Arterioscler Thromb Vasc Biol. 2002 Jun 1;22(6):1012-7 - PubMed
  13. Haematologica. 2009 May;94(5):693-9 - PubMed
  14. Circulation. 1999 Aug 17;100(7):717-22 - PubMed
  15. Thromb Res. 2005;116(1):1-13 - PubMed
  16. Arch Pathol Lab Med. 1993 Jan;117(1):67-70 - PubMed
  17. Ann Intern Med. 2008 Oct 7;149(7):481-90, W94 - PubMed
  18. Thromb Haemost. 1999 Aug;82(2):626-33 - PubMed
  19. Arch Intern Med. 2008 Nov 10;168(20):2245-53 - PubMed
  20. J Am Heart Assoc. 2014 Jan 02;3(1):e000467 - PubMed
  21. Thromb Haemost. 2008 Jan;99(1):246-8 - PubMed
  22. Thromb Haemost. 2002 Jan;87(1):47-51 - PubMed
  23. Blood. 2010 Jul 8;116(1):113-21 - PubMed
  24. Thromb Res. 2015 Oct;136(4):781-5 - PubMed
  25. JAMA. 2004 Apr 14;291(14):1701-12 - PubMed
  26. JAMA. 2002 Jul 17;288(3):321-33 - PubMed
  27. Arterioscler Thromb Vasc Biol. 2006 Dec;26(12):2807-12 - PubMed
  28. JAMA. 2004 Oct 6;292(13):1573-80 - PubMed
  29. J Thromb Haemost. 2014 Jun;12(6):879-86 - PubMed
  30. Arch Intern Med. 2006 Apr 10;166(7):772-80 - PubMed
  31. Arterioscler Thromb Vasc Biol. 1999 Apr;19(4):893-9 - PubMed
  32. Ann Intern Med. 2010 Oct 19;153(8):523-31 - PubMed
  33. Circulation. 2005 Nov 29;112(22):3495-500 - PubMed
  34. J Clin Epidemiol. 2003 Jun;56(6):598-603 - PubMed
  35. J Clin Oncol. 2009 Sep 1;27(25):4124-9 - PubMed

Publication Types

Grant support