Thromb Haemost 2000; 83(04): 530-535
DOI: 10.1055/s-0037-1613857
Commentary
Schattauer GmbH

Thrombotic Variables and Risk of Idiopathic Venous Thromboembolism in Women Aged 45-64 Years

Relationships to Hormone Replacement Therapy
Gordon Lowe
1   From the University Department of Medicine, Royal Infirmary, Glasgow, UK
,
Mark Woodward
2   Department of Applied Statistics, University of Reading, UK
,
Martin Vessey
3   Department of Public Health, University of Oxford, UK
,
Ann Rumley
1   From the University Department of Medicine, Royal Infirmary, Glasgow, UK
,
Parimala Gough
3   Department of Public Health, University of Oxford, UK
,
Edel Daly
3   Department of Public Health, University of Oxford, UK
› Author Affiliations
We thank the British Heart Foundation for financial support (Grant PG/95008); and Ruth Simpson and Alycia Murray for typing the manuscript.
Further Information

Publication History

Received 18 June 1999

Accepted after revision 30 November 1999

Publication Date:
27 December 2017 (online)

Summary

Hormone replacement therapy (HRT) has been shown to increase the relative risk of idiopathic venous thromboembolism (VTE) about threefold in several observational studies and one randomised controlled trial. Whether or not this relative risk is higher in women with underlying thrombophilia phenotypes, such as activated protein C (APC) resistance, is unknown. We therefore restudied the participants in a case-control study of the relationship between the use of HRT and the occurrence of idiopathic VTE in women aged 45-64 years. After protocol exclusions, 66 of the cases in the original study and 163 of the controls were studied. Twenty haematological variables relevant to risk of VTE were analysed, including thrombotic states defined from the literature. The relative risk of VTE showed significant associations with APC resistance (OR 4.06; 95% CI 1.62, 10.21); low antithrombin (3.33; 1.15, 9.65) or protein C (2.93; 1.06, 8.14); and high coagulation factor IX (2.34; 1.26, 4.35), or fibrin D-dimer (3.84; 1.99, 7.42). HRT use increased the risk of VTE in women without any of these thrombotic states (OR 4.09; 95% CI 1.26, 13.30). A similar effect of HRT use on the relative risk of VTE was also found in women with prothrombotic states. Thus for example, the combination of HRT use and APC resistance increased the risk of VTE about 13-fold compared with women of similar age without either APC resistance or HRT use (OR 13.27; 95% CI 4.30, 40.97).

We conclude that the combination of HRT use and thrombophilias (especially if multiple) increases the relative risk of VTE substantially; hence women known to have thrombophilias (especially if multiple) should be counselled about this increased risk prior to prescription of HRT. However, HRT increases the risk of VTE about fourfold even in women without any thrombotic abnormalities: possible causes are discussed.

 
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