Hormone replacement therapy leads to increased plasma levels of platelet derived microparticles in postmenopausal women
- 243 Downloads
Whereas prevention of cardiovascular diseases by hormonal replacement therapy is still part of an ongoing debate, well-defined data are available relating hormonal replacement therapy to an elevated risk of venous thrombosis and embolism. Although it seems that venous thrombosis in patients treated with hormonal replacement therapy is linked to changes in plasmatic coagulation, less is known about the role of platelet-derived microparticles, as well as endothelial cell-derived microparticles.
Patients and methods
In this prospective case–control study, levels of microparticles were investigated in postmenopausal women receiving hormone replacement therapy (n = 15) and compared to age-matched controls (n = 15).
Total count of microparticles and the subgroup of microparticles derived from endothelial cells did not differ in the investigated groups. In contrast, median levels of microparticles derived from platelet/megacaryocyte were higher in women taking hormonal replacement therapy (5,244 × 106/l) than in controls (2,803 × 106/l; p = 0.040). Furthermore, hormonal replacement therapy led to a higher plasma level of microparticles derived from activated platelets, exposing P-selectin (136 × 106/l vs. 58 × 106/l; p = 0.011), or exposing CD63 (171 × 106 vs. 91 × 106/l; p = 0.011) compared to the control group.
Higher concentrations of microparticles derived from (activated) platelets/megacaryocytes were present in postmenopausal women taking hormonal replacement therapy. This finding indicates a procoagulant state in these women and might play a role in the development of venous side effects. In contrast, levels of endothelial cell-derived microparticles did not differ.
KeywordsHormone replacement therapy Microparticle Venous thrombosis
- 2.Bagger YZ, Tanko LB, Alexandersen P, Hansen HB, Mollgaard A, Ravn P, Qvist P, Kanis JA, Christiansen C (2004) Two to three years of hormone replacement treatment in healthy women have long-term preventive effects on bone mass and osteoporotic fractures: the PERF study. Bone 34:728–735PubMedCrossRefGoogle Scholar
- 3.(1997) Collaborative Group on Hormonal Factors in Breast Cancer: breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52,705 women with breast cancer and 108,411 women without breast cancer. Lancet 350:1047–1059Google Scholar
- 22.Sims PJ, Wiedmer T, Esmon CT, Weiss HJ, Shattil SJ (1988) Assembly of the platelet prothrombinase complex is linked to vesiculation of the platelet plasma membrane. Studies in Scott syndrome: an isolated defect in platelet procoagulant activity. J Biol Chem 264(29):17049–17057Google Scholar
- 23.Kuriyama N, Nagakane Y, Hosomi A, Ohara T, Kasai T, Harada S, Takeda K, Yamada K, Ozasa K, Tokuda T, Watanabe Y, Mizuno T, Nakagawa M (2010) Evaluation of factors associated with elevated levels of platelet-derived microparticles in the acute phase of cerebral infarction. Clin Appl Thromb Hemost 16(1):26–32PubMedCrossRefGoogle Scholar
- 30.Berckmans RJ, Nieuwland R, Böing AN, Romijn FP, Hack CE, Sturk A (2001) Cell-derived microparticles circulate in healthy humans and support low grade thrombin generation. Thromb Haemost 83:639–646Google Scholar
- 31.Bal L, Ederhy S, Di Angelantonio E, Toti F, Zobairi F, Dufaitre G, Meuleman C, Mallat Z, Boccara F, Tedgui A, Freyssinet JM, Cohen A (2010) Factors influencing the level of circulating procoagulant microparticles in acute pulmonary embolism. Arch Cardiovasc Dis 103(6–7):394–403PubMedCrossRefGoogle Scholar
- 33.Ramacciotti E, Hawley AE, Farris DM, Ballard NE, Wrobleski SK, Myers DD Jr, Henke PK, Wakefield TW (2009) Leukocyte- and platelet-derived microparticles correlate with thrombus weight and tissue factor activity in an experimental mouse model of venous thrombosis. Thromb Haemost 101(4):748–754PubMedGoogle Scholar
- 47.Corada M, Liao F, Lindgren M, Lampugnani MG, Breviario F, Frank R, Muller WA, Hicklin DJ, Bohlen P, Dejana E (2001) Monoclonal antibodies directed to different regions of vascular endothelial cadherin extracellular domain affect adhesion and clustering of the protein and modulate endothelial permeability. Blood 97(6):1679–1684PubMedCrossRefGoogle Scholar
- 49.Koga H, Sugiyama S, Kugiyama K, Watanabe K, Fukushima H, Tanaka T, Sakamoto T, Yoshimura M, Jinnouchi H, Ogawa H (2005) Elevated levels of VE-cadherin-positive endothelial microparticles in patients with type 2 diabetes mellitus and coronary artery disease. J Am Coll Cardiol 45:1622–1630PubMedCrossRefGoogle Scholar