Does the Presence of Uterine Fibroids Cause Changes in the Blood That Increase the Risk of Clots?

Uterine Fibroids (UF) are benign uterine tumours, also known as leiomyomas. They are estimated to affect up to 80% of women of reproductive age. UF more commonly occur in women of Afro-Caribbean ethnicity. UF may be asymptomatic or associated with a range of symptoms including menorrhagia, dysmenorrhea, sub-fertility, and pressure symptoms.

An association between Venous Thromboembolic disease and UF has been inferred in case reports, series, and one population-based study. The true prevalence and the full scale of the problem is unknown. As UF are so prevalent, in many women, the apparent association reflects the presence of known risk factors for Venous Thromboembolism (VTE) such as thrombophilia, smoking and significant co-morbidities such as cancer. Thrombosis and UF have also been shown to have common risk factors, such as obesity and age. Hormonal therapies, which are often used to treat the symptoms of UF, can also increase the risk of VTE.

However, in a subset of women with VTE and UF, no thrombophilia or acquired risk factors for VTE can be identified. In most of the reported case studies, bulky tumours cause extrinsic compression of pelvic vessels, venous stasis and thus thrombosis. A clinical case review reported by our centre has identified women with thrombosis and UF that do not cause local venous stasis and no additional risk factors for thrombosis. This suggests that there may be additional pathogenic mechanisms underlying the development of thrombosis in individuals with UF. A second centre has also published a case review, similarly identifying an apparent association between UF and thrombosis in the absence of venous stasis.

Clot structure and function is dictated by the conditions present during fibrin generation. Endogenous thrombin production, cellular components and fibrinogen structure are all implicated in altering clot structure and function. There are several plausible mechanisms via which UF may affect thrombin generation, clot formation and structure to generate a pro-thrombotic state. The fibroid tumours may secrete Transforming Growth Factor ß3 (TGF- ß3) and this appears to influence production of thrombomodulin, antithrombin III and plasminogen activator inhibitor 1, all of which can modify the blood's haemostatic capacity and may result in a pro-thrombotic phenotype.

Alternatively, fibroids may mediate an indirect pro-thrombotic effect by inducing iron deficiency anaemia. Iron deficiency anaemia has been associated in numerous case studies and series with thrombotic events, most commonly cerebral venous thrombosis, but also Pulmonary Embolism (PE) and Deep Vein Thrombosis (DVT). Iron deficiency anaemia may also cause a reactive elevation in erythropoietin thrombocytosis, thrombopoietin and FVIII resulting in enhanced thrombin generation. In the proposed study we will exclude participants with moderate and severe anaemia to identify whether any pro-thrombotic phenotype identified is caused by a mechanism other than anaemia.