Aim

akusherstvo

Obstetrics, Gynecology and Reproduction

Акушерство, Гинекология и Репродукция

2313-73472500-3194

IRBIS LLC

10.17749/2313-7347/ob.gyn.rep.2021.105

akusherstvo-931

Research Article

Original articles

ОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ

Use of plasmapheresis in treatment of patients with unfavorable anamnestic pregnancy outcomes coupled to antiphospholipid antibodies

Использование плазмафереза в лечении пациенток с неблагоприятными исходами беременностей в анамнезе и наличием антифосфолипидных антител

https://orcid.org/0000-0003-4512-9599

Еремеева

Д. Р.

Eremeeva

D. R.

Еремеева Дина Рустемовна - кандидат медицинских наук, ассистент кафедры акушерства, гинекологии и репродуктологии ПСПбГМУ им. акад. И.П. Павлова МЗ РФ; заместитель главного врача СПб ГБУЗ «Родильный дом № 6 имени профессора В.Ф. Снегирева».197022 Санкт-Петербург, ул. Льва Толстого, д. 6/8; 192014 Санкт-Петербург, ул. Маяковского, д. 5.

Dina R. Eremeeva - MD, PhD, Assistant, Department of Obstetrics, Gynecology and Reproductive Medicine, Pavlov First Saint Petersburg State Medical University; Deputy of Head Physician, Snegirev Maternity Hospital № 6.6/8 Lev Tolstoy Str., Saint Petersburg 197022; 5 Mayakovskogo Str., Saint Petersburg 192014.

dina-bikmullina@yandex.ru

https://orcid.org/0000-0002-2622-5000

Зайнулина

М. С.

Zainulina

M. S.

Зайнулина Марина Сабировна - доктор медицинских наук, профессор кафедры акушерства, гинекологии и репродуктологии ПСПбГМУ им. акад. И.П. Павлова МЗ РФ; главный врач СПб ГБУЗ «Родильный дом № 6 имени профессора В.Ф. Снегирева».197022 Санкт-Петербург, ул. Льва Толстого, д. 6/8; 192014 Санкт-Петербург, ул. Маяковского, д. 5.Scopus Author ID: 37076359000Researcher ID: B-5746-2018

Marina S. Zainulina - MD, Dr Sci Med, Professor, Department of Obstetrics, Gynecology and Reproductive Medicine, Pavlov First Saint Petersburg State Medical University; Head Physician, Snegirev Maternity Hospital № 6.6/8 Lev Tolstoy Str., Saint Petersburg 197022; 5 Mayakovskogo Str., Saint Petersburg 192014.Scopus Author ID: 37076359000Researcher ID: B-5746-2018

https://orcid.org/0000-0001-7516-530X

Долгова

Ю. С.

Dolgova

Yu. S.

Долгова Юлия Сергеевна - старший лаборант кафедры акушерства, гинекологии и репродуктологии ПСПбГМУ им. акад. И.П. Павлова МЗ РФ; врач акушер-гинеколог СПб ГБУЗ «Родильный дом № 6 имени профессора В.Ф. Снегирева».197022 Санкт-Петербург, ул. Льва Толстого, д. 6/8; 192014 Санкт-Петербург, ул. Маяковского, д. 5.

Yulia S. Dolgova - MD, Senior Assistant, Department of Obstetrics, Gynecology and Reproductive Medicine, Pavlov First Saint Petersburg State Medical University; Obstetrician-Gynecologist, Obstetric Department of Pregnancy Pathology, Snegirev Maternity Hospital № 6.6/8 Lev Tolstoy Str., Saint Petersburg 197022; 5 Mayakovskogo Str., Saint Petersburg 192014.

https://orcid.org/0000-0003-2450-7044

Шахалиев

Р. A.

Shakhaliev

R. A.

Шахалиев Рустам Алигисмет Оглы - клинический ординатор кафедры акушерства, гинекологии и репродуктологии.197022 Санкт-Петербург, ул. Льва Толстого, д. 6/8.

Rustam A. Shakhaliev - MD, Clinical Resident, Department of Obstetrics, Gynecology and Reproductive Medicine, Pavlov First Saint Petersburg State Medical University.6/8 Lev Tolstoy Str., Saint Petersburg 197022.

https://orcid.org/0000-0003-4128-1542

Сильванович

О. А.

Silvanovich

O. A.

Сильванович Ольга Алексеевна – студент.194100 Санкт-Петербург, Литовская ул., д. 2.

Olga A. Silvanovich - Student, Saint Petersburg State Pediatric Medical University.2 Litovskaya Str., Saint Petersburg 194100.

https://orcid.org/0000-0003-1203-0533

Павлова

Л. А.

Pavlova

L. A.

Павлова Лада Александровна – студент.194100 Санкт-Петербург, Литовская ул., д. 2.

Lada A. Pavlova - Student, Saint Petersburg State Pediatric Medical University.2 Litovskaya Str., Saint Petersburg 194100.

Первый Санкт-Петербургский государственный медицинский университет имени академика И.П. Павлова Министерства здравоохранения Российской Федерации; Родильный дом № 6 имени профессора В.Ф. СнегиреваРоссияPavlov First Saint Petersburg State Medical University, Health Ministry of Russian Federation; Snegirev Maternity Hospital № 6Russian Federation

Первый Санкт-Петербургский государственный медицинский университет имени академика И.П. Павлова Министерства здравоохранения Российской ФедерацииРоссияPavlov First Saint Petersburg State Medical University, Health Ministry of Russian FederationRussian Federation

Санкт-Петербургский государственный педиатрический медицинский университет Министерства здравоохранения Российской ФедерацииРоссияSaint Petersburg State Pediatric Medical University, Health Ministry of Russian FederationRussian Federation

2021

06032021

1512231

2021

Еремеева Д.Р., Зайнулина М.С., Долгова Ю.С., Шахалиев Р.A., Сильванович О.А., Павлова Л.А.

Eremeeva D.R., Zainulina M.S., Dolgova Y.S., Shakhaliev R.A., Silvanovich O.A., Pavlova L.A.

Данная работа распространяется под лицензией Creative Commons Attribution 4.0.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://www.gynecology.su/jour/article/view/931

Aim

Aim: to evaluate efficacy of plasmapheresis combined with low molecular weight heparins (LMWH) and acetylsalicylic acid (ASA).

Materials and Methods

Materials and Methods. 327 plasmapheresis sessions were performed for 75 patients: 17 (22.6 %) patients during preparation for pregnancy, 11 (19.0 %) pregnant women in the first trimester, 33 (56.9 %) pregnant women in the second trimester, and 34 (58.6 %) pregnant women in the third trimester. Study inclusion criteria were as follows: high titers of antiphospholipid antibodies (APA) as well as included non-inclusion criteria in pregnant women with miscarriages and unfavorable anamnestic pregnancy outcome. 36 (62.1 %) women had pregnancy loss in anamnesis. All patients received low-dose ASA and LMWH therapy; 15 (25.86 %) pregnant women also received courses of intravenous immunoglobulins in the first and second trimesters.Results. 47 pregnant women had delivery, whereas 10 of women had pregnancy in progress. Term delivery was in 40 (85.1 %) patients, so that 23 (48.9 %) pregnant women had delivery per vias naturales. The average weight of the fetus was 3364.00 ± 393.76 g, height - 52.13 ± 1.82 cm. In 100 % cases, Apgar score was 8 points. 24 (51.1%) pregnant women had delivery via cesarean section. The average blood loss comprised 528.64 ± 166.10 ml. The average fetal weight in group after surgical delivery was 2982.14 ± 582.88 g, average height - 49.14 ± 4.09 cm, the Apgar score - 7.69 ± 0.47 points. Preterm births were observed in 7 (14.9%) cases, all via cesarean section. In 1 case, early fetal death was at gestational age of 8/9 weeks; according to the karyotyping data, a fetal chromosomal abnormality was detected. No severe obstetric complications were observed.Conclusions. Combining plasmapheresis with low dose LMWH and ASA therapy demonstrated high efficacy in treating obstetric APS manifested as high percentage of favorable pregnancy outcomes and low number of obstetric complications.

Цель исследования: оценить эффективность применения плазмафереза в комбинации с терапией низкомолекулярными гепаринами (НМГ) и ацетилсалициловой кислотой (АСК) у женщин с высокими титрами антифосфолипидных антител (АФА) и повторными акушерскими потерями.Материалы и методы. Проведено 327 сеансов плазмафереза 75 пациенткам: на этапе подготовки к беременности -17 (22,6 %) женщинам, в I триместре - 11 (19,0 %) беременным, во II триместре - 33 (56,9 %) беременным, в III триместре - 34 (58,6 %) беременным. Критерием включения в исследование явилось наличие высоких титров как критериальных, так и некритериальных АФА у беременных с потерями и неблагоприятными исходами беременности в анамнезе. У 36 (62,1 %) женщин имелись потери беременности в анамнезе. Все пациентки получали терапию низкими дозами АСК и НМГ, 15 (25,86 %) беременных также получали курсы внутривенных иммуноглобулинов в I и II триместрах.Результаты. Родоразрешено 47 беременных, у 10 беременность на данный момент прогрессирует. Роды в срок прошли у 40 (85,1 %) пациенток, у 23 (48,9 %) беременных роды прошли через естественные родовые пути. Средний вес плода составил 3364,00 ± 393,76 г, рост - 52,13 ± 1,82 см. Оценка по шкале Апгар в 100 % случаев составила 8 баллов. Путем операции кесарева сечения родоразрешены 24 (51,1 %) беременные. Средняя кровопотеря при оперативном родоразре-шении составила 528,64 ± 166,10 мл. Средний вес плода в группе родоразрешенных оперативным путем составил 2982,14 ± 582,88 г, средний рост - 49,14 ± 4,09 см, оценка по шкале Апгар - 7,69 ± 0,47 балла. Преждевременные роды произошли в 7 (14,9 %) случаях, все - путем операции кесарева сечения. В одном случае беременность замерла при сроке 8/9 нед; по результатам кариотипирования абортного материала обнаружена хромосомная аномалия плода. Тяжелых акушерских осложнений не наблюдалось ни в одном случае.Заключение. Комбинация плазмафереза с НМГ и АСК показала высокую эффективность в лечении акушерского антифос-фолипидного синдрома - высокий процент благоприятных исходов беременности, отсутствие тяжелых акушерских осложнений.

антифосфолипидный синдромплазмаферезнизкомолекулярные гепаринывнутривенные иммуноглобулиныпривычное невынашивание

antiphospholipid syndromeplasmapheresislow molecular weight heparinsintravenous immunoglobulinsrecurrent pregnancy loss

References1

Cervera R., Piette J.C., Font J. et al. Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis Rheum. 2002;46(4):1019-27. https://doi.org/10.1002/art.10187.

Miyakis S., Lockshin M.D., Atsumi T. et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006;4(2):295-306. https://doi.org/10.1111/j.1538-12.7836.2006.01753.x.

Sciascia S., Sanna G., Murru V. et al. Anti-prothrombin (aPT) and antiphosphatidylserine/prothrombin (aPS/PT) antibodies and the risk of thrombosis in the antiphospholipid syndrome. A systematic review. Thromb Haemost. 2014;111(2):354-64. https://doi.org/10.1160/TH13-06-0509.

Reynaud Q., Lega J.C., Mismetti P. et al. Risk of venous and arterial thrombosis according to type of antiphospholipid antibodies in adults without systemic lupus erythematosus: A systematic review and metaanalysis. Autoimm Rev. 2014;13(6):595-608. https://doi.org/10.1016/j.autrev.2013.11.004.

Hoxha A., Mattia E., Tonello M. et al. Antiphosphatidylserine/prothrombin antibodies as biomarkers to identify severe primary antiphospholipid syndrome. Clin Chem Lab Med. 2017;55(6):890-8. https://doi.org/10.1515/cclm-2016-0638.

Becarevic M. The IgG and IgM isotypes of anti-annexin A5 antibodies: relevance for primary antiphospholipid syndrome. J Thromb Thrombolysis. 2016;42(4):552-7. https://doi.org/10.1007/s11239-016-1389-5.

Sebire N.J., Fox H., Backos M. et al. Defective endovascular trophoblast invasion in primary antiphospholipid antibody syndrome-associated early pregnancy failure. Hum Reprod. 2002;17(4):1067-71. https://doi.org/10.1093/humrep/17.4.1067.

Di Simone N., Marana R., Castellani R. et al. Decreased expression of heparin-binding epidermal growth factor-like growth factor as a newly identified pathogenic mechanism of antiphospholipid-mediated defective placentation. Arthritis Rheum. 2010;62(5):1504-12. https://doi.org/10.1002/art.27361.

Abrahams V.M., Chamley L.W., Salmon J.E. Emerging treatment models in rheumatology: antiphospholipid syndrome and pregnancy: pathogenesis to translation. Arthritis Rheum. 2017;69(9):1710-21. https://doi.org/10.1002/art.40136.

D'Ippolito S., Meroni P.L., Koike T. et al. Obstetric antiphospholipid syndrome: a recent classification for an old defined disorder. Autoimmun Rev. 2014;13(9):901-8. https://doi.org/10.1016/j.autrev.2014.05.004.

Holers V.M., Girardi G., Mo L. et al. Complement C3 activation is required for antiphospholipid antibody-induced fetal loss. J Exp Med. 2002;195(2):211-20. https://doi.org/10.1084/jem.200116116.

Levine A.B., Lockshin M.D. Antiphospholipid syndrome. In: Contraception and pregnancy in patients with rheumatic disease. Eds. L.R. Sammaritano, B.L. Bermas. New York, NY: Springer, 2014. 109-137.

Ruffatti A., Favaro M., Calligaro A. et al. Management of pregnant women with antiphospholipid antibodies. Expert Rev Clin Immunol. 2019;15(4):347-58. https://doi.org/10.1080/1744666X.2019.1565995.

Rai R., Cohen H., Dave M., Regan L. Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies). BMJ. 1997;314(7076):253-7. https://doi.org/10.1136/bmj.314.7076.253.

Mak A., Cheung M.W., Cheak A.A., Ho R.C. Combination of heparin and aspirin is superior to aspirin alone in enhancing live births in patients with recurrent pregnancy loss and positive anti-phospholipid antibodies: a meta-analysis of randomized controlled trials and meta-regression. Rheumatology (Oxford). 2010;49(2):281-8. https://doi.org/10.1093/rheumatology/kep373.

Bates S.M., Greer I.A., Middeldorp S. et al. VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e691S-e736S. https://doi.org/10.1378/chest.11-2300.

Gris J.C., Bouvier S., Molinari N. et al. Comparative incidence of a first thrombotic event in purely obstetric antiphospholipid syndrome with pregnancy loss: the NOH-APS observational study. Blood. 2012;119(11):2624-32. https://doi.org/10.1182/blood-2011-09-381913.

Thomsen A.J., Greer I.A. Thromboembolic disease in pregnancy and the puerperium: acute management (Green-top guideline no. 37b). Royal College of Obstetricians and Gynaecologists, 2015. 32 p. Available at: https://www.rcog.org.uk/globalassets/documents/guidelines/gtg-37b.pdf. [Accessed: 12.12.2019].

Bao S.H., Sheng S.L., Liao H. et al. Use of D-dimer measurement to guide anticoagulant treatment in recurrent pregnancy loss associated with antiphospholipid syndrome. Am J Reprod Immunol. 2017;78(6):e12770. https://doi.org/10.1111/aji.12770.

Erkan D., Patel S., Nuzzo M. et al. Management of the controversial aspects of the antiphospholipid syndrome pregnancies: a guide for clinicians and researchers. Rheumatology (Oxford). 2008;47(Suppl 3):iii23-7. https://doi.org/10.1093/rheumatology/ken181.

Ruffatti A., Salvan E., Del Ross T. et al. Treatment strategies and pregnancy outcomes in antiphospholipid syndrome patients with thrombosis and triple antiphospholipid positivity: a European multicentre retrospective study. Thromb Haemost. 2014;112(6):727-35. https://doi.org/10.1160/TH14120001.

Bramham K., Thomas M., Nelson-Piercy C. et al. First-trimester low-dose prednisolone in refractory antiphospholipid antibody-related pregnancy loss. Blood. 2011;117(25):6948-51. https://doi.org/10.1182/blood-2011-02-339234.

Mekinian A., Lazzaroni M.G., Kuzenko A. et al. The efficacy of hydroxychloroquine for obstetrical outcome in anti-phospholipid syndrome: data from a European multicenter retrospective study. Autoimmun Rev. 2015;14(6):498-502. https://doi.org/10.1016/j.autrev.2015.01.012.

Sciascia S., Hunt B.J., Talavera-Garcia E. et al. The impact of hydroxychloroquine treatment on pregnancy outcome in women with antiphospholipid antibodies. Am J Obstet Gynecol. 2016;214(2):273. e1-273.e8. https://doi.org/10.1016/j.ajog.2015.09.078.

Bertolaccini M.L., Contento G., Lennen R. et al. Complement inhibition by hydroxychloroquine prevents placental and fetal brain abnormalities in antiphospholipid syndrome. J Autoimmun. 2016;75:30-38. https://doi.org/10.1016/j.jaut.2016.04.008.

Mekinian A., Alijotas-Reig J., Carrat F. et al. Refractory obstetrical antiphospholipid syndrome: features, treatment and outcome in a European multicenter retrospective study. Autoimmun Rev. 2017;16(7):730-4. https://doi.org/10.1016/j.autrev.2017.05.006.

Saccone G., Berghella V., Maruotti G.M. et al. Antiphospholipid antibody profile based obstetric outcomes of primary antiphospholipid syndrome: the PREGNANTS study. Am J Obstet Gynecol. 2017;216(5):525.e1-525. e12. https://doi.org/10.1016/j.ajog.2017.01.026.

Empson M., Lassere M., Craig J., Scott J. Prevention of recurrent miscarriage for women with antiphospholipid antibody or lupus anticoagulant. Cochrane Database Syst Rev. 2005;18(2):CD002859. https://doi.org/10.1002/14651858.CD002859.pub2.

Tenti S., Cheleschi S., Guidelli G.M. et al. Intravenous immunoglobulins and antiphospholipid syndrome: how, when and why? A review of the literature. Autoimmun Rev. 2016;15(3):226-35. https://doi.org/10.1016/j.autrev.2015.11.009.

Branch D.W., Peaceman A.M., Druzin M. et al. A multicenter, placebo-controlled pilot study of intravenous immune globulin treatment of antiphospholipid syndrome during pregnancy. The Pregnancy Loss Study Group. Am J Obstet Gynecol. 2000;181(1 Pt 1):122-7. https://doi.org/10.1016/s0002-9378(00)70500-x.

Nakamura Y., Yoshida K., Itoh S. et al. Immunoadsorption plasmapheresis as a treatment for pregnancy complicated by systemic lupus erythematosus with positive antiphospholipid antibodies. Am J Reprod Immunol. 1999;41(5):307-11. https://doi.org/10.1111/j.1600-0897.1999.tb00443.x.

Bortolati M., Marson P., Chiarelli S. et al. Case reports of the use of immunoadsorption or plasma exchange in high-risk pregnancies of women with antiphospholipid syndrome. Ther Apher Dial. 2009;13(2):157-60. https://doi.org/10.1111/j.1744-9987.2009.00671.x.

Hauser A.C., Hauser L., Pabinger-Fasching I. et al. The course of anticardiolipin antibody levels under immunoadsorption therapy. Am J Kidney Dis. 2005;46(3):446-54. https://doi.org/10.1053/j.ajkd.2005.05.023.

El-Haieg D.O., Zanati M.F., El-Foual F.M. Plasmapheresis and pregnancy outcome in patients with antiphospholipid syndrome. Int J Gynaecol Obstet. 2007;99(3):236-41. https://doi.org/10.1016/j.ijgo.2007.05.045.

Ruffatti A., Marson P., Pengo V. et al. Plasma exchange in the management of high risk pregnant patients with primary antiphospholipid syndrome. A report of 9 cases and a review of the literature. Autoimmun Rev. 2007;6(3):196-202. https://doi.org/10.1016/j.autrev.2006.11.002.

Rose H.L., Ho W.K. Management of very high risk pregnancy with secondary anti-phospholipid syndrome and triple positivity to the antiphospholipid antibodies. J Thromb Thrombolysis. 2014;38(4):453-6. https://doi.org/10.1007/s11239-014-1080-7.

Mayer-Pickel K., Horn S., Lang U., Cervar-Zivkovic M. Response to plasmapheresis measured by angiogenic factors in a woman with antiphospholipid syndrome in pregnancy. Case Rep Obstet Gynecol. 2015;2015:123408. https://doi.org/10.1155/2015/123408.

Ruffatti A., Favaro M., Hoxha A. et al. Apheresis and intravenous immunoglobulins used in addition to conventional therapy to treat high-risk pregnant antiphospholipid antibody syndrome patients. A prospective study. J Reprod Immunol. 2016;115:14-9. https://doi.org/10.1016/j.jri.2016.03.004.

The authors declare that there are no conflicts of interest present.