Oral contraceptives, hormone replacement therapy, thrombophilias and risk of venous thromboembolism: A systematic review. The Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) Study

Department of Obstetrics and Gynaecology, University of Glasgow, Glasgow Royal Infirmary, 10 Alexandra Parade, Glasgow G31 2ER, UK.
Thrombosis and Haemostasis (Impact Factor: 4.98). 08/2005; 94(1):17-25. DOI: 10.1160/TH04-11-0759
Source: PubMed


Combined oral contraceptives, oral hormone replacement therapy and thrombophilias are recognised risk factors for venous thromboembolism in women. The objective of this study was to assess the risk of thromboembolism among women with thrombophilia who are taking oral contraceptives or hormone replacement therapy, conducting a systematic review and metaanalysis. Of 201 studies identified, only nine met the inclusion criteria. Seven studies included pre-menopausal women on oral contraceptives and two studies included peri-menopausal women on hormone replacement therapy. For oral contraceptive use, significant associations of the risk of venous thromboembolism were found in women with factor V Leiden (OR 15.62; 95%CI 8.66 to 28.15); deficiencies of antithrombin (OR 12.60; 95%CI 1.37 to 115.79), protein C (OR 6.33; 95%CI 1.68 to 23.87), or protein S (OR 4.88; 95%CI 1.39 to 17.10), elevated levels of factor VIIIc (OR 8.80; 95%CI 4.13 to 18.75); and factor V Leiden and prothrombin G20210A (OR 7.85; 95%CI 1.65 to 37.41). For hormone replacement therapy, a significant association was found in women with factor V Leiden (OR 13.16; 95%CI 4.28 to 40.47). Although limited by the small number of studies, the findings of this study support the presence of interaction between thrombophilia and venous thromboembolism among women taking oral contraceptives. However, further studies are required to establish with greater confidence the associations of these, and other, thrombophilias with venous thromboembolism among hormone users.

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    • "Increasing evidence also indicates a central role of prothrombotic changes in the blood, referred to as thrombophilia, in the pathogenesis of unprovoked DVT [4]. However, most of the to date established contributors to thrombophilia, like the presence of heterozygous factor V Leiden-or prothrombin mutation, have been shown to increase the propensity of developing venous thromboembolism (VTE) only moderately [5]. Tissue factor (TF) is a transmembrane receptor and the main in-vivo initiator of blood coagulation. "
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    ABSTRACT: Background: Tissue factor (TF) is the main in-vivo initiator of blood coagulation. Microparticles (MPs) are small procoagulant membrane vesicles. Elevated TF-bearing MPs have been found in different prothrombotic conditions and MP-associated TF activity may contribute to the pathogenesis of unprovoked deep vein thrombosis (DVT). Objective: To determine MP-TF activity levels at diagnosis of DVT and at four additional time points during the course of one year in a well-defined group of patients with unprovoked DVT of the lower limb. Patients/Methods: In this study, 41 patients with acute unilateral symptomatic and unprovoked DVT of the lower limb were included and followed for 1 year. Venous blood samples for determination of MP-TF activity were drawn at diagnosis of acute DVT, and 1-, 3-, 6-, and 12 months later. In addition, 10 young and healthy control subjects were included. Results: The median MP-TF activity was 0.06 pg/mL (25th-75th percentile: 0.0-0.53) in patients with acute DVT and 0.18 pg/mL (0.07-0.33) in healthy controls, and did not differ significantly (p = 0.35). No significant changes in MP-TF activity were found in the follow-up measurements. MP-TF activity did also not differ significantly between patients with proximal-or distal DVT and between those with-or without residual DVT after 6 months. Conclusions: MP-TF activity is low at the acute event in patients with unprovoked DVT of the lower limb and remains unchanged during the course of the disease. Our data do not support the hypothesis that TF-bearing MPs play a determining role in the pathogenesis of unprovoked DVT.
    Thrombosis Research 08/2014; 134(5). DOI:10.1016/j.thromres.2014.07.041 · 2.45 Impact Factor
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    • "The most studied interaction however, in this respect, is that between carriership of the FVLeiden mutation and the use of oral contraceptives (OC) (Vandenbroucke et al, 1994, 2001; Wu et al, 2005; van Hylckama Vlieg, 2009). Given the world-wide use of OC, this is an interaction of great importance. "
    Thrombophilia, 11/2011; , ISBN: 978-953-307-872-4
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    • "The covariates used in all analyses were age, sex, age2, age × sex, age2× sex, oral contraceptive use (i.e., exogenous hormone use), and menopause status. Age, sex, oral contraception, and menopause status are each known to have a significant effect on the risk of CVD in general [29, 30], and, in some cases, these associations seem related to D-dimer levels [6–8]. "
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    ABSTRACT: Background. D-dimer is associated with increasing severity of atherosclerosis and with increased risk of a cardiovascular disease (CVD). Methods and Results. To better understand this risk factor, we performed a genome scan on 803 (301 males and 502 females) Mexican Americans in the San Antonio Family Heart Study (SAFHS). The SAFHS is ideal for the discovery of quantitative trait loci (QTLs) influencing CVD because CVD risk factors are prevalent in Mexican Americans of San Antonio and because the study design involves large families, which is optimal for QTL discovery. D-dimer levels were normalized in our study. We found that D-dimer levels were heritable, at about 23% heritability (P ≈ .00001). In a linkage analysis employing 432 microsatellite markers, we found strong evidence of a QTL on chromosome 5p with a lod score of 3.32 at 21 centiMorgans (cM). We also found suggestive evidence of a QTL on chromosome 2q with a lod score of 2.33 at 207 cM. Conclusions. To our knowledge, the putative QTL on chromosome 5p is novel. The possible QTL on chromosome 2q is discussed in relation to a recent report of linkage of a related hemostatic factor to the same location. These results warrant further investigation.
    International journal of vascular medicine 06/2010; 2010:490241. DOI:10.1155/2010/490241
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