Thrombotic variables and risk of idiopathic venous thromboembolism in women aged 45-64 years - Relationships to hormone replacement therapy

Hormone replacement therapy (HRT) has been shown to increase the relative r isk of idiopathic venous thromboembolism (VTE) about threefold in several o bservational studies and one randomised controlled trial. Whether or not th is relative risk is higher in women with underlying thrombophilia phenotype s, such as activated protein C (APC) resistance, is unknown. We therefore r estudied the participants in a case-control study of the relationship betwe en 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 (2.3 4: 1.26, 1.35), or fibrin D-dimer (3.84; 1.99, 7.32). HRT use increased the risk of VTE in women without any of these thrombotic static; (OR 4.09; 95% CI 1.26, 13.30). A similar effect of HRT use on the relative risk of VTE w as also found in women with prothrombotic states. Thus for example, the com bination of HRT use and APC resistance increased the risk of VTE about 13-f old 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 increa ses the risk of VTE about fourfold even in women without any thrombotic abn ormalities: possible causes an discussed.