Hemostasis in women with obesity and metabolic syndrome
DOI: 10.32364/2587-6821-2021-5-9-598-604
I.A. Kuzina, E.V. Goncharova, N.S. Martirosyan, M.E. Telnova, Yu.A. Atamanova,
K.A. Yudina, N.A. Petunina
N.V. Sklifosovskiy Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation
To date, obesity is a global epidemic that resulted in increased morbidity and mortality, including those associated with thrombotic conditions. Metabolic syndrome (MS) is characterized by abdominal obesity, glucose metabolism disorders, hypertension, and dyslipidemia. Patients with MS have higher risks of thrombosis and cardiovascular events. Hemostatic disorders in women with obesity and MS are an important clinical issue. Hemostatic abnormalities in these patients (hypercoagulation, hypofibrinolysis, platelet dysfunctions) increase the risk of cardiovascular morbidity and mortality and venous thromboembolism (VTE). Combined oral contraceptives (COCs) increase VTE risk in women with obesity. During pregnancy and postnatal period, obesity is one of the most common causes of VTE. In postmenopause, obesity and MS, and COCs prescribed as menopausal hormone therapy require close attention in controlling hemostatic parameters. This paper reviews significant hemostatic abnormalitie s in obesity and MS and discusses the role of these conditions in developing hemostatic disorders and VTE in women of reproductive age and postmenopause.
Keywords: obesity, metabolic syndrome, hemostasis, combined oral contraceptives, pregnancy, postmenopause, venous thromboembolism.
For citation: Kuzina I.A., Goncharova E.V., Martirosyan N.S. et al. Hemostasis in women with obesity and metabolic syndrome. Russian Medical Inquiry. 2021;5(9):598–604 (in Russ.). DOI: 10.32364/2587-6821-2021-5-9-598-604.
About the authors:
Irina A. Kuzina — assistant of the Department of Endocrinology of the N.V. Sklifosovskiy Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University); 11 Build. 2, Rossolimo str., Moscow, 119021, Russian Federation; ORCID iD 0000-0001-7923-4894.
Ekaterina V. Goncharova — C. Sc. (Med.), associate professor of the Department of Endocrinology of the N.V. Sklifosovskiy Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University); 11 Build. 2, Rossolimo str., Moscow, 119021, Russian Federation; ORCID iD 0000-0001-7025-8427.
Narine S. Martirosyan — C. Sc. (Med.), associate professor of the Department of Endocrinology of the N.V. Sklifosovskiy Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University); 11 Build. 2, Rossolimo str., Moscow, 119021, Russian Federation; ORCID iD 0000-0002-0202-1257.
Milena E. Telnova — C. Sc. (Med.), associate professor of the Department of Endocrinology of the N.V. Sklifosovskiy Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University); 11 Build. 2, Rossolimo str., Moscow, 119021, Russian Federation; ORCID iD 0000-0001-8007-9721.
Yuliya A. Atamanova — student of the 6th course, I.M. Sechenov First Moscow State Medical University (Sechenov University); 8 Build. 2, Trubetskaya str., Moscow, 119991, Russian Federation; ORCID iD 0000-0001-6401-3470.
Kseniya A. Yudina — student of the 6th course, I.M. Sechenov First Moscow State Medical University (Sechenov University); 8 Build. 2, Trubetskaya str., Moscow, 119991, Russian Federation; ORCID iD 0000-0002-5386-0691.
Nina A. Petunina — Dr. Sc. (Med.), Professor, Corresponding Member of the RAS, Head of the Department of Endocrinology of the N.V. Sklifosovskiy Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University); 11 Build. 2, Rossolimo str., Moscow, 119021, Russian Federation; ORCID iD 0000-0001-9390-1200.
Contact information: Irina A. Kuzina, e-mail:
mia986@mail.ru.
Financial Disclosure: no authors have a financial or property interest in any material or method mentioned.
There is no conflict of interests.
Received 23.08.2021.
Revised 15.09.2021.
Accepted 08.10.2021.
2. WHO. Global action plan for the prevention and control of noncommunicable diseases 2013–2020. Geneva, Switzerland: World Health Organization; 2013.
3. Sharma A.M. M, M, M and M: A mnemonic for assessing obesity. Obes Rev. 2010;11:808–809. DOI: 10.1111/j.1467-789X.2010.00766.x.
4. Keltz J., Zapantis A., Jindal S.K. et al. Overweight men: clinical pregnancy after ART is decreased in IVF but not in ICSI cycles. J Assist Reprod Genet. 2010;27(9–10):539–544. DOI: 10.1007/s10815-010-9439-y.
5. Alberti K.G., Zimmet P., Shaw J. Metabolic syndrome — a new world-wide definition. A Consensus Statement from the International Diabetes Federation. Diabet Med. 2006;23(5):469–480. DOI: 10.1111/j.1464-5491.2006.01858.x.
6. Ивашкин В.Т., Драпкина О.М., Корнеева О.М. Клинические варианты метаболического синдрома. М.: МИА; 2011. [Ivashkin V.T., Drapkina O.M., Korneyeva O.M. Clinical variants of metabolic syndrome. M.: MIA; 2011 (in Russ.)].
7. Adeoye A.M., Adewoye I.A., Dairo D.M. et al. Excess Metabolic Syndrome Risks Among Women Health Workers Compared With Men. J Clin Hypertens (Greenwich). 2015;17(11):880–884. DOI: 10.1111/jch.12595.
8. Olinto M.T.A., Theodoro H., Canuto R. Epidemiology of abdominal obesity. In: Gordeladze J., ed. Adiposity — epidemiology and treatment modalities. IntechOpen; 2017.
9. Say L., Chou D., Gemmill A. et al. Global causes of maternal deaths: a WHO systematic analysis. Lancet Glob Health. 2014;2(6):e329–e338. DOI: 10.1016/S2214-109X(14)70227-X.
10. Rath W., Tsikouras P. Mütter sterbefälle weltweit rückläufig, aber häufig vermeidbar! Z Geburtshilfe Neonatol. 2018;222(4):143–151 (in German). DOI: 10.1055/a-0607-2816.
11. Sonnevi K., Tchaikovski S.N., Holmström M. et al. Obesity and thrombin-generation profiles in women with venous thromboembolism. Blood Coagul Fibrinolysis. 2013;24(5):547–553. DOI: 10.1097/MBC.0b013e32835f93d5.
12. Konukoglu D., Uzun H. Endothelial dysfunction and hypertension. Adv Exp Med Biol. 2017;956:511–540. DOI: 10.1007/5584_2016_90.
13. Adya R., Tan B.K., Randeva H.S. Differential effects of leptin and adiponectin in endothelial angiogenesis. J Diabetes Res. 2015;2015:648239. DOI: 10.1155/2015/648239.
14. Сидоркина А.Н., Сидоркин В.Г., Преснякова М.В. Биохимические основы системы гемостаза и диссеминированное внутрисосудистое свертывание крови. Изд. 4-е. Нижний Новгород: ННИИТО; 2008. [Sidorkina A.N., Sidorkin V.G., Presnyakova M.V. Biochemical basis of the hemostasis system and disseminated intravascular coagulation. 4th edition. Nizhny Novgorod: NNIITO; 2008 (in Russ).].
15. Напалкова О.С., Эмануэль В.Л., Лапин С.В. и др. Тромбин как ключевой фермент гемостаза и его роль в атеросклерозе и воспалении. Медицинский алфавит. 2015;3(11):42–45. [Napalkova O.S., Emanuel V.L., Karpenko M.A. et al. Thrombin as key enzyme of hemostasis and its role in atherosclerosis and inflammation. Meditsinskiy alfavit. 2015;3(11):42–45 (in Russ)].
16. Vilahur G., Ben-Aicha S., Badimon L. New insights into the role of adipose tissue in thrombosis. Cardiovasc Res. 2017;113(9):1046–1054. DOI: 10.1093/cvr/cvx086.
17. Kearney K., Tomlinson D., Smith K., Ajjan R. Hypofibrinolysis in diabetes: a therapeutic target for the reduction of cardiovascular risk. Cardiovasc Diabetol. 2017;16(1):34. DOI: 10.1186/s12933-017-0515-9.
18. Ekpenyong C.E. Relationship between insulin resistance and metabolic syndrome clusters: current knowledge. Acta Sci Med Sci. 2019;3(3):99–104.
19. Pedro-Botet J., Ascaso J.F., Barrios V. et al. COSMIC project: consensus on the objectives of the metabolic syndrome in clinic. Diabetes Metab Syndr Obes. 2018;11:683–697. DOI: 10.2147/DMSO.S165740.
20. Morange P.E., Alessi M.C. Thrombosis in central obesity and metabolic syndrome: mechanisms and epidemiology. Thromb Haemost. 2013;110(10):669–680. DOI: 10.1160/TH13-01-0075.
21. Xie W., Zhai Z., Yang Y. et al. Free fatty acids inhibit TM-EPCR expression through JNK pathway: an implication for the development of the prothrombotic state in metabolic syndrome. J Thromb Thrombolysis. 2012;34:468–474. DOI: 10.1007/s11239-012-0793-8.
22. Rudnicka A.R., Rumley A., Whincup P.H. et al. Sex differences in the relationship between inflammatory and hemostatic biomarkers and metabolic syndrome: British 1958 Birth Cohort. J Thromb Haemost. 2011;9(12):2337–2344. DOI: 10.1111/j.1538-7836.2011.04517.
23. Heit J.A., Spencer F.A., White R.H. The epidemiology of venous thromboembolism. J Thromb Thrombolysis. 2016;41(1):3–14. DOI: 10.1007/s11239-015-1311-6.
24. Gialeraki A., Valsami S., Pittaras T. et al. Oral Contraceptives and HRT Risk of Thrombosis. Clin Appl Thromb Hemost. 2018;24(2):217–225. DOI: 10.1177/1076029616683802.
25. Sandset P.M. Mechanisms of hormonal therapy related thrombosis. Thromb Res. 2013;131(suppl 1):S4–S7. DOI: 10.1016/S0049-3848(13)70009-4.
26. Lidegaard O. Hormonal contraception, thrombosis and age. Expert Opin Drug Saf. 2014;13(10):1353–1360. DOI: 10.1517/14740338.2014.950654.
27. George A.P., Kent P. The Impact of multiple risk factors for venous thromboembolism and its implications for management. Glob Pediatr Health. 2019;6:2333794X19859161. DOI: 10.1177/2333794X19859161.
28. Horton L.G., Simmons K.B., Curtis K.M. Combined hormonal contraceptive use among obese women and risk for cardiovascular events: A systematic review. Contraception. 2016;94(6):590–604. DOI: 10.1016/j.contraception.2016.05.014.
29. Malinowski A.K., Bomba-Opoń D., Parrish J. et al. Venous thromboembolism in obese pregnant women: approach to diagnosis and management. Ginekologia polska. 2017;88(8):453–45. DOI: 10.5603/GP.a2017.0083 9.
30. Morgan E.S., Wilson E., Melody T. et al. An observational study of haemostatic changes, leptin and soluble endoglin during pregnancy in women with different BMIs. Blood Coagul Fibrinolysis. 2017;28(1):50–55. DOI: 10.1097/MBC.0000000000000535.
31. Heit J.A., Spencer F.A., White R.H. The epidemiology of venous thromboembolism. J Thromb Thrombolysis. 2016;41(1):3–14. DOI: 10.1007/s11239-015-1311-6.
32. Sucker C. Prophylaxis and therapy of venous thrombotic events (VTE) in pregnancy and the postpartum period. Geburtshilfe Frauenheilkd. 2020;80(1):48–59. DOI: 10.1055/a-1030-4546.
33. Morgan E.S., Wilson E., Watkins T. et al. Maternal obesity and venous thromboembolism. Int J Obstet Anesth. 2012;21:253–263. DOI: 10.1016/j.ijoa.2012.01.002.
34. Braekkan S.K., Siegerink B., Lijfering W.M. et al. Role of obesity in the etiology of deep vein thrombosis and pulmonary embolism: current epidemiological insights. Semin Thromb Hemost. 2013;39(5):533–540. DOI: 10.1055/s-0033-1343355.
35. Stewart F.M., Freeman D.J., Ramsay J.E. et al. Longitudinal assessment of maternal endothelial function and markers of inflammation and placental function throughout pregnancy in lean andobese mothers. J Clin Endocrinol Metab. 2007;92:969–975. DOI: 10.1210/jc.2006-2083.
36. Butwick A.J., Bentley J., Leonard S.A. et al. Prepregnancy maternal body mass index and venous thromboembolism: a population-based cohort study. BJOG. 2019;126(5):581–588. DOI: 10.1111/1471-0528.15567.
37. ESHRE Capri Workshop Group, Eichinger S., Evers J.L.H., Glasieer A. et al. Venous thromboembolism in women: a specific reproductive health risk. Hum Reprod Update. 2013;19(5):471–482. DOI: 10.1093/humupd/dmt028.
38. Giannini A., Caretto M., Genazzani A.R., Simoncini T. Menopause, Hormone Replacement Therapy (HRT) and Obesity. Curre Res Diabetes and Obes J. 2018;7(1):555704. DOI: 10.19080/CRDOJ.2018.07.555704.
39. Palla G., Ramírez-Morán C., Montt-Guevara M.M. et al. Perimenopause, body fat, metabolism and menopausal symptoms in relation to serum markers of adiposity, inflammation and digestive metabolism. J Endocrinol Invest. 2020;43(6):809–820. DOI: 10.1007/s40618-019-01168-6.
40. Basurto L., Díaz A., Rodriguez A. et al. Circulating levels of plasminogen activator inhibitor-1 are associated with metabolic syndrome rather than with menopause. Gynecol Endocrinol. 2019;35(10):909–912. DOI: 10.1080/09513590.2019.1604658.
41. Rossouw J.E., Anderson G.L., Prentice R.L. et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial. JAMA. 2002;288(3):321–333. DOI: 10.1001/jama.288.3.321.
42. Scarabin P.Y. Hormone therapy and venous thromboembolism among postmenopausal women. Front Horm Res. 2014;43:21–32. DOI: 10.1159/000360554.
43. Rott H. Prevention and treatment of venous thromboembolism during HRT: current perspectives. Int J Gen Med. 2014;7:433–440. DOI: 10.2147/IJGM.S46310.
44. Canonico M., Oger E., Conard J. et al. Obesity and risk of venous thromboembolism among postmenopausal women: differential impact of hormone therapy by route of estrogen administration. The ESTHER Study. J Thromb Haemost. 2006;4(6):1259–1265. DOI: 10.1111/j.1538-7836.2006.01933.x.
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