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Конфаундинг-факторы первичных венозных тромбозов и эмболий, ассоциированных с репродуктивным поведением женщин
Конфаундинг-факторы первичных венозных тромбозов и эмболий, ассоциированных с репродуктивным поведением женщин
Белокриницкая Т.Е., Фролова Н.И., Галыгин Е.В. и др. Конфаундинг-факторы первичных венозных тромбозов и эмболий, ассоциированных с репродуктивным поведением женщин. Гинекология. 2016; 18 (2): 67–70.
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Аннотация
Цель исследования – выявить основные конфаундинг-факторы первичных венозных тромбозов и эмболий, ассоциированных с репродуктивным поведением женщин.
Материал и методы. Проведен ретроспективный анализ факторов риска венозных тромбоэмболических осложнений (ВТЭО) у 53 женщин репродуктивного возраста (18–45 лет), не имеющих тяжелой соматической патологии и тромбозов в анамнезе.
Результаты. У 67,9% пациенток основными триггерами первичных ВТЭО явились прием комбинированных оральных контрацептивов – КОК (43,4%) и беременность/послеродовый период (24,5%). Наиболее распространенными кофакторами риска были варикозное расширение вен нижних конечностей (79,2%), возраст старше 35 лет (62,4%), малоподвижный образ жизни (60,4%), курение и ожирение (по 33,9%), отягощенный семейный анамнез по тромбозам/генетически подтвержденная тромбофилия (20,8%). Среднее число фоновых факторов риска у пользовательниц КОК составило 3,4±0,1, у беременных – 3,7±0,2, у родильниц – 5,0±0,1.
Заключение. При назначении КОК, при планировании и ведении беременности/послеродового периода необходимо помнить о повышенном риске ВТЭО, тщательно оценивать уже имеющиеся факторы риска и принимать все меры по их предупреждению.
Ключевые слова: конфаундинг-факторы, венозные тромбозы, беременность, гормональная контрацепция.
Subjects and methods. Retrospective analysis of risk factors for venous thromboembolic events (VTEEs) was made in 53 reproductive-aged (18–45-year-old) women with no history of severe somatic diseases and thromboses.
Results. In 67.9% of the patients, the major triggers of primary VTEEs were the use of combined oral contraceptive (COC) pills (43.4%) and pregnancy/postpartum (24.5%). The most common cofactors were lower extremity varices (79.2%), over 35 years of age (62.4%), a sedentary lifestyle (60.4%), smoking (33.9%), obesity (33.9%), and positive family history of thromboses/genetically verified thrombophilia (20.8%). The mean number of background risk factors was 3.4±0.1 in COC users, 3.7±0.2 in pregnant women, and 5.0±0.1 in puerperas.
Conclusion. When prescribing COC pills, planning, and managing pregnancy/postpartum, it is necessary to keep in mind that the risk of VTEEs is increased, to thoroughly assess the already existing risk factors, and to take every measure for their prevention.
Key words: confounding factors, venous thromboses, pregnancy, hormonal contraception.
Материал и методы. Проведен ретроспективный анализ факторов риска венозных тромбоэмболических осложнений (ВТЭО) у 53 женщин репродуктивного возраста (18–45 лет), не имеющих тяжелой соматической патологии и тромбозов в анамнезе.
Результаты. У 67,9% пациенток основными триггерами первичных ВТЭО явились прием комбинированных оральных контрацептивов – КОК (43,4%) и беременность/послеродовый период (24,5%). Наиболее распространенными кофакторами риска были варикозное расширение вен нижних конечностей (79,2%), возраст старше 35 лет (62,4%), малоподвижный образ жизни (60,4%), курение и ожирение (по 33,9%), отягощенный семейный анамнез по тромбозам/генетически подтвержденная тромбофилия (20,8%). Среднее число фоновых факторов риска у пользовательниц КОК составило 3,4±0,1, у беременных – 3,7±0,2, у родильниц – 5,0±0,1.
Заключение. При назначении КОК, при планировании и ведении беременности/послеродового периода необходимо помнить о повышенном риске ВТЭО, тщательно оценивать уже имеющиеся факторы риска и принимать все меры по их предупреждению.
Ключевые слова: конфаундинг-факторы, венозные тромбозы, беременность, гормональная контрацепция.
________________________________________________
Subjects and methods. Retrospective analysis of risk factors for venous thromboembolic events (VTEEs) was made in 53 reproductive-aged (18–45-year-old) women with no history of severe somatic diseases and thromboses.
Results. In 67.9% of the patients, the major triggers of primary VTEEs were the use of combined oral contraceptive (COC) pills (43.4%) and pregnancy/postpartum (24.5%). The most common cofactors were lower extremity varices (79.2%), over 35 years of age (62.4%), a sedentary lifestyle (60.4%), smoking (33.9%), obesity (33.9%), and positive family history of thromboses/genetically verified thrombophilia (20.8%). The mean number of background risk factors was 3.4±0.1 in COC users, 3.7±0.2 in pregnant women, and 5.0±0.1 in puerperas.
Conclusion. When prescribing COC pills, planning, and managing pregnancy/postpartum, it is necessary to keep in mind that the risk of VTEEs is increased, to thoroughly assess the already existing risk factors, and to take every measure for their prevention.
Key words: confounding factors, venous thromboses, pregnancy, hormonal contraception.
Полный текст
Список литературы
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8. Hormonal Contraception and Risk of Venous Thromboembolism (VTE). Position statement. SOGC.19February2013.6p. https://docviewer. yandex.ru/r.xml?sk=56f543ccbba21f958ba121e8a866e60c&url=http%3A%2F%2Fsogc.org%2Fwp-content%2Fuploads%2F2013%2F04%2 FmedHormonalContraceptionVTE1302192.pdf
9. Petersen JF, Bergholt T, Nielsen AK et al. Combined hormonal contraception and risk of venous thromboembolism within the first year following pregnancy. Danish nationwide historical cohort 1995–2009. Thromb Haemost 2014; 112 (1): 73–8.
10. Squizzato A, Van Zaane B, Gerdes VE, Büller HR. The influence of pituitary, adrenal, and parathyroid hormones on hemostasis and thrombosis. Semin Thromb Hemost 2011; 37 (1): 41–8.
11. Kyriakakis N, Lynch J, Ajjan R, Murray RD. The effects of pituitary and thyroid disorders on haemostasis: potential clinical implications. Clin Endocrinol (Oxf) 2016; 84 (4): 473–84.
12. Wahlberg J, Tillmar L, Ekman B et al. Effects of prolactin on platelet activation and blood clotting. Scand J Clin Lab Invest 2013; 73 (3): 221–8.
13. Van Zaane B, Squizzato A, Reuwer AQ et al. Prolactin and Venous Thrombosis Indications for a Novel Risk Factor? Arterioscler Thromb Vasc Biol 2011; 31: 672–7.
14. Bitzer J. Statement on combined hormonal contraceptives containing third- or fourth-generation progestogens or cyproterone acetate, and the associated risk of thromboembolism. Eur J Contracept Reprod Health Care 2013; 18: 143–7.
15. Bergendal A, Persson I, Odeberg J et al. Association of venous thromboembolism with hormonal contraception and thrombophilic genotypes. Obstet Gynecol 2014; 124 (3): 600–9.
16. Evans G, Sutton EL. Oral contraception. Med Clin North Am 2015; 99 (3): 479–503.
17. http://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/cyproterone_ethinylestradiol...
18. Медицинские критерии приемлемости методов контрацепции РФ. Адаптированный документ «Медицинские критерии приемлемости использования методов контрацепции ВОЗ, 4 издание, 2009». М., 2012. / Meditsinskie kriterii priemlemosti metodov kontratseptsii RF. Adaptirovannyiy dokument «Meditsinskie kriterii priemlemosti ispolzovaniya metodov kontratseptsii VOZ, 4 izdanie, 2009». M., 2012. [in Russian]
19. Кесарево сечение. Показания, методы обезболивания, хирургическая техника, антибиотикопрофилактика, ведение послеоперационного периода. Клинические рекомендации (протокол) утв. МЗ РФ 27 мая 2014 года №15-4\10\2-3185. М., 2014. / Kesarevo sechenie. Pokazaniya, metodyi obezbolivaniya, hirurgicheskaya tehnika, antibiotikoprofilaktika, vedenie posleoperatsionnogo perioda. Klinicheskie rekomendatsii (protokol) utv. MZ RF 27 maya 2014 goda №15-4102-3185. M., 2014. [in Russian]
20. Jensen TB, Gerds TA, Grøn R et al. Risk factors for venous thromboembolism during pregnancy. Pharmacoepidemiol Drug Saf 2013; 22 (12): 1283–91.
2. Say L, Chou D, Gemmill A et al. Global causes of maternal death: a WHO systematic analysis. Lancet Global Health 2014; 2 (6): 323–33.
3. Rossiyskie klinicheskie rekomendatsii po diagnostike, lecheniyu i profilaktike venoznyih tromboembolicheskih oslojneniy. Flebologiya. 2010; 4 (2). [in Russian]
4. Gourbil M, Grandvuillemin A, Beyens MN et al. Thromboembolic events in women exposed to hormonal contraception or cyproterone acetate in 2012: a cross-sectional observational study in 30 French public hospitals. Drug Saf 2014; 37 (4): 269–82.
5. Heit JA. Epidemiology of venous thromboembolism. Nat Rev Cardiol 2015; 12 (8): 464–74.
6. Profilaktika venoznyih tromboembolicheskih oslojneniy v akusherstve i ginekologii. Klinicheskie rekomendatsii (protokol) utv. MZ RF 27 maya 2014 goda №15-4102-3792. M., 2014. [in Russian]
7. Dinger J, Heinemann LA, Kühl-Habich D. The safety of a drospirenone-containing oral contraceptive: final results from the European Active Surveillance Study on oral contraceptives based on 142,475 women-years. Contraception 2007; 75 (5): 344–54.
8. Hormonal Contraception and Risk of Venous Thromboembolism (VTE). Position statement. SOGC.19February2013.6p. https://docviewer. yandex.ru/r.xml?sk=56f543ccbba21f958ba121e8a866e60c&url=http%3A%2F%2Fsogc.org%2Fwp-content%2Fuploads%2F2013%2F04%2 FmedHormonalContraceptionVTE1302192.pdf
9. Petersen JF, Bergholt T, Nielsen AK et al. Combined hormonal contraception and risk of venous thromboembolism within the first year following pregnancy. Danish nationwide historical cohort 1995–2009. Thromb Haemost 2014; 112 (1): 73–8.
10. Squizzato A, Van Zaane B, Gerdes VE, Büller HR. The influence of pituitary, adrenal, and parathyroid hormones on hemostasis and thrombosis. Semin Thromb Hemost 2011; 37 (1): 41–8.
11. Kyriakakis N, Lynch J, Ajjan R, Murray RD. The effects of pituitary and thyroid disorders on haemostasis: potential clinical implications. Clin Endocrinol (Oxf) 2016; 84 (4): 473–84.
12. Wahlberg J, Tillmar L, Ekman B et al. Effects of prolactin on platelet activation and blood clotting. Scand J Clin Lab Invest 2013; 73 (3): 221–8.
13. Van Zaane B, Squizzato A, Reuwer AQ et al. Prolactin and Venous Thrombosis Indications for a Novel Risk Factor? Arterioscler Thromb Vasc Biol 2011; 31: 672–7.
14. Bitzer J. Statement on combined hormonal contraceptives containing third- or fourth-generation progestogens or cyproterone acetate, and the associated risk of thromboembolism. Eur J Contracept Reprod Health Care 2013; 18: 143–7.
15. Bergendal A, Persson I, Odeberg J et al. Association of venous thromboembolism with hormonal contraception and thrombophilic genotypes. Obstet Gynecol 2014; 124 (3): 600–9.
16. Evans G, Sutton EL. Oral contraception. Med Clin North Am 2015; 99 (3): 479–503.
17. http://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/cyproterone_ethinylestradiol...
18. Meditsinskie kriterii priemlemosti metodov kontratseptsii RF. Adaptirovannyiy dokument «Meditsinskie kriterii priemlemosti ispolzovaniya metodov kontratseptsii VOZ, 4 izdanie, 2009». M., 2012. [in Russian]
19. Kesarevo sechenie. Pokazaniya, metodyi obezbolivaniya, hirurgicheskaya tehnika, antibiotikoprofilaktika, vedenie posleoperatsionnogo perioda. Klinicheskie rekomendatsii (protokol) utv. MZ RF 27 maya 2014 goda №15-4102-3185. M., 2014. [in Russian]
20. Jensen TB, Gerds TA, Grøn R et al. Risk factors for venous thromboembolism during pregnancy. Pharmacoepidemiol Drug Saf 2013; 22 (12): 1283–91.
2. Say L, Chou D, Gemmill A et al. Global causes of maternal death: a WHO systematic analysis. Lancet Global Health 2014; 2 (6): 323–33.
3. Российские клинические рекомендации по диагностике, лечению и профилактике венозных тромбоэмболических осложнений. Флебология. 2010; 4 (2). / Rossiyskie klinicheskie rekomendatsii po diagnostike, lecheniyu i profilaktike venoznyih tromboembolicheskih oslojneniy. Flebologiya. 2010; 4 (2). [in Russian]
4. Gourbil M, Grandvuillemin A, Beyens MN et al. Thromboembolic events in women exposed to hormonal contraception or cyproterone acetate in 2012: a cross-sectional observational study in 30 French public hospitals. Drug Saf 2014; 37 (4): 269–82.
5. Heit JA. Epidemiology of venous thromboembolism. Nat Rev Cardiol 2015; 12 (8): 464–74.
6. Профилактика венозных тромбоэмболических осложнений в акушерстве и гинекологии. Клинические рекомендации (протокол) утв. МЗ РФ 27 мая 2014 года №15-4\10\2-3792. М., 2014. / Profilaktika venoznyih tromboembolicheskih oslojneniy v akusherstve i ginekologii. Klinicheskie rekomendatsii (protokol) utv. MZ RF 27 maya 2014 goda №15-4102-3792. M., 2014. [in Russian]
7. Dinger J, Heinemann LA, Kühl-Habich D. The safety of a drospirenone-containing oral contraceptive: final results from the European Active Surveillance Study on oral contraceptives based on 142,475 women-years. Contraception 2007; 75 (5): 344–54.
8. Hormonal Contraception and Risk of Venous Thromboembolism (VTE). Position statement. SOGC.19February2013.6p. https://docviewer. yandex.ru/r.xml?sk=56f543ccbba21f958ba121e8a866e60c&url=http%3A%2F%2Fsogc.org%2Fwp-content%2Fuploads%2F2013%2F04%2 FmedHormonalContraceptionVTE1302192.pdf
9. Petersen JF, Bergholt T, Nielsen AK et al. Combined hormonal contraception and risk of venous thromboembolism within the first year following pregnancy. Danish nationwide historical cohort 1995–2009. Thromb Haemost 2014; 112 (1): 73–8.
10. Squizzato A, Van Zaane B, Gerdes VE, Büller HR. The influence of pituitary, adrenal, and parathyroid hormones on hemostasis and thrombosis. Semin Thromb Hemost 2011; 37 (1): 41–8.
11. Kyriakakis N, Lynch J, Ajjan R, Murray RD. The effects of pituitary and thyroid disorders on haemostasis: potential clinical implications. Clin Endocrinol (Oxf) 2016; 84 (4): 473–84.
12. Wahlberg J, Tillmar L, Ekman B et al. Effects of prolactin on platelet activation and blood clotting. Scand J Clin Lab Invest 2013; 73 (3): 221–8.
13. Van Zaane B, Squizzato A, Reuwer AQ et al. Prolactin and Venous Thrombosis Indications for a Novel Risk Factor? Arterioscler Thromb Vasc Biol 2011; 31: 672–7.
14. Bitzer J. Statement on combined hormonal contraceptives containing third- or fourth-generation progestogens or cyproterone acetate, and the associated risk of thromboembolism. Eur J Contracept Reprod Health Care 2013; 18: 143–7.
15. Bergendal A, Persson I, Odeberg J et al. Association of venous thromboembolism with hormonal contraception and thrombophilic genotypes. Obstet Gynecol 2014; 124 (3): 600–9.
16. Evans G, Sutton EL. Oral contraception. Med Clin North Am 2015; 99 (3): 479–503.
17. http://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/cyproterone_ethinylestradiol...
18. Медицинские критерии приемлемости методов контрацепции РФ. Адаптированный документ «Медицинские критерии приемлемости использования методов контрацепции ВОЗ, 4 издание, 2009». М., 2012. / Meditsinskie kriterii priemlemosti metodov kontratseptsii RF. Adaptirovannyiy dokument «Meditsinskie kriterii priemlemosti ispolzovaniya metodov kontratseptsii VOZ, 4 izdanie, 2009». M., 2012. [in Russian]
19. Кесарево сечение. Показания, методы обезболивания, хирургическая техника, антибиотикопрофилактика, ведение послеоперационного периода. Клинические рекомендации (протокол) утв. МЗ РФ 27 мая 2014 года №15-4\10\2-3185. М., 2014. / Kesarevo sechenie. Pokazaniya, metodyi obezbolivaniya, hirurgicheskaya tehnika, antibiotikoprofilaktika, vedenie posleoperatsionnogo perioda. Klinicheskie rekomendatsii (protokol) utv. MZ RF 27 maya 2014 goda №15-4102-3185. M., 2014. [in Russian]
20. Jensen TB, Gerds TA, Grøn R et al. Risk factors for venous thromboembolism during pregnancy. Pharmacoepidemiol Drug Saf 2013; 22 (12): 1283–91.
________________________________________________
2. Say L, Chou D, Gemmill A et al. Global causes of maternal death: a WHO systematic analysis. Lancet Global Health 2014; 2 (6): 323–33.
3. Rossiyskie klinicheskie rekomendatsii po diagnostike, lecheniyu i profilaktike venoznyih tromboembolicheskih oslojneniy. Flebologiya. 2010; 4 (2). [in Russian]
4. Gourbil M, Grandvuillemin A, Beyens MN et al. Thromboembolic events in women exposed to hormonal contraception or cyproterone acetate in 2012: a cross-sectional observational study in 30 French public hospitals. Drug Saf 2014; 37 (4): 269–82.
5. Heit JA. Epidemiology of venous thromboembolism. Nat Rev Cardiol 2015; 12 (8): 464–74.
6. Profilaktika venoznyih tromboembolicheskih oslojneniy v akusherstve i ginekologii. Klinicheskie rekomendatsii (protokol) utv. MZ RF 27 maya 2014 goda №15-4102-3792. M., 2014. [in Russian]
7. Dinger J, Heinemann LA, Kühl-Habich D. The safety of a drospirenone-containing oral contraceptive: final results from the European Active Surveillance Study on oral contraceptives based on 142,475 women-years. Contraception 2007; 75 (5): 344–54.
8. Hormonal Contraception and Risk of Venous Thromboembolism (VTE). Position statement. SOGC.19February2013.6p. https://docviewer. yandex.ru/r.xml?sk=56f543ccbba21f958ba121e8a866e60c&url=http%3A%2F%2Fsogc.org%2Fwp-content%2Fuploads%2F2013%2F04%2 FmedHormonalContraceptionVTE1302192.pdf
9. Petersen JF, Bergholt T, Nielsen AK et al. Combined hormonal contraception and risk of venous thromboembolism within the first year following pregnancy. Danish nationwide historical cohort 1995–2009. Thromb Haemost 2014; 112 (1): 73–8.
10. Squizzato A, Van Zaane B, Gerdes VE, Büller HR. The influence of pituitary, adrenal, and parathyroid hormones on hemostasis and thrombosis. Semin Thromb Hemost 2011; 37 (1): 41–8.
11. Kyriakakis N, Lynch J, Ajjan R, Murray RD. The effects of pituitary and thyroid disorders on haemostasis: potential clinical implications. Clin Endocrinol (Oxf) 2016; 84 (4): 473–84.
12. Wahlberg J, Tillmar L, Ekman B et al. Effects of prolactin on platelet activation and blood clotting. Scand J Clin Lab Invest 2013; 73 (3): 221–8.
13. Van Zaane B, Squizzato A, Reuwer AQ et al. Prolactin and Venous Thrombosis Indications for a Novel Risk Factor? Arterioscler Thromb Vasc Biol 2011; 31: 672–7.
14. Bitzer J. Statement on combined hormonal contraceptives containing third- or fourth-generation progestogens or cyproterone acetate, and the associated risk of thromboembolism. Eur J Contracept Reprod Health Care 2013; 18: 143–7.
15. Bergendal A, Persson I, Odeberg J et al. Association of venous thromboembolism with hormonal contraception and thrombophilic genotypes. Obstet Gynecol 2014; 124 (3): 600–9.
16. Evans G, Sutton EL. Oral contraception. Med Clin North Am 2015; 99 (3): 479–503.
17. http://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/cyproterone_ethinylestradiol...
18. Meditsinskie kriterii priemlemosti metodov kontratseptsii RF. Adaptirovannyiy dokument «Meditsinskie kriterii priemlemosti ispolzovaniya metodov kontratseptsii VOZ, 4 izdanie, 2009». M., 2012. [in Russian]
19. Kesarevo sechenie. Pokazaniya, metodyi obezbolivaniya, hirurgicheskaya tehnika, antibiotikoprofilaktika, vedenie posleoperatsionnogo perioda. Klinicheskie rekomendatsii (protokol) utv. MZ RF 27 maya 2014 goda №15-4102-3185. M., 2014. [in Russian]
20. Jensen TB, Gerds TA, Grøn R et al. Risk factors for venous thromboembolism during pregnancy. Pharmacoepidemiol Drug Saf 2013; 22 (12): 1283–91.
Авторы
Т.Е.Белокриницкая*1, Н.И.Фролова1, Е.В.Галыгин2, Д.Б.Нардин2, Е.Ю.Морозов3
1. ГБОУ ВПО Читинская государственная медицинская академия Минздрава России.
672090, Россия, Чита, ул. Горького, д. 39а;
2. ГУЗ Краевая клиническая больница. 672038, Россия, Чита, ул. Коханского, д. 7а;
3. ГУЗ Городская клиническая больница №1. 672039, Россия, Чита, ул. Ленина, д. 8
*tanbell24@mail.ru
1. Chita State Medical Academy of the Ministry of Health of the Russian Federation. 672090, Russian Federation, Chita, ul. Gor'kogo, d. 39a;
2. Regional Clinical Hospital. 672038, Russian Federation, Chita, ul. Kokhanskogo, d. 7a;
3. City Clinical Hospital №1. 672039, Russian Federation, Chita, ul. Lenina, d. 8
*tanbell24@mail.ru
1. ГБОУ ВПО Читинская государственная медицинская академия Минздрава России.
672090, Россия, Чита, ул. Горького, д. 39а;
2. ГУЗ Краевая клиническая больница. 672038, Россия, Чита, ул. Коханского, д. 7а;
3. ГУЗ Городская клиническая больница №1. 672039, Россия, Чита, ул. Ленина, д. 8
*tanbell24@mail.ru
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1. Chita State Medical Academy of the Ministry of Health of the Russian Federation. 672090, Russian Federation, Chita, ul. Gor'kogo, d. 39a;
2. Regional Clinical Hospital. 672038, Russian Federation, Chita, ul. Kokhanskogo, d. 7a;
3. City Clinical Hospital №1. 672039, Russian Federation, Chita, ul. Lenina, d. 8
*tanbell24@mail.ru
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