Ulyanovsk Medico-biological Journal

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DOI: 10.23648/UMBJ.2017.28.8742

УДК 618.3-008.64

 

ВОЛЧАНОЧНЫЙ АНТИКОАГУЛЯНТ – ПРЕДИКТОР НЕБЛАГОПРИЯТНЫХ ИСХОДОВ БЕРЕМЕННОСТИ

 

Р.Н. Степанова, А.С. Косова

ФГБОУ ВО «Орловский государственный университет им. И.С. Тургенева», г. Орел, Россия

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В последние годы широко обсуждается вопрос о причастности аутоиммунной патологии к потере плода и другим осложнениям беременности. «Обвиняемым» в этом признают аутоантитело к антигенным детерминантам фосфолипидов клеточных мембран – волчаночный антикоагулянт (ВА).

Цель исследований – идентификация у беременных женщин биомаркера аутоиммунных нарушений ВА, определение его значения в прогнозировании плохих исходов беременности, оценка профилактической эффективности антиагрегантных доз ацетилсалициловой кислоты и дипиридамола, назначенных ВА-положительным беременным.

Материалы и методы. В группу повышенного риска неблагоприятного исхода беременности вошли 125 женщин, госпитализированных с угрожающим выкидышем. В акушерском анамнезе пациенток отмечено от 2 до 8 ранних абортов, а также преэклампсия (ПЭ). Всех женщин тестировали по клинической классификации системной красной волчанки Американской ревматологической ассоциации. Присутствие ВА в венозной крови пациенток определяли тестом коагуляции разведенным тканевым тромбопластином (РТТ). ВА-положительные женщины принимали 125 мг/день ацетилсалициловой кислоты и 150 мг/день дипиридамола.

Результаты. По тесту РТТ ВА-позитивными оказались 62 (49,6 %) пациентки. В 8 (7,8 %) случаях развилась тяжелая ПЭ, в 6 – у ВА-позитивных женщин. Профилактические назначения соблюдали 24 ВА-положительные женщины. Настоящая беременность у них завершилась срочными родами, у 3 (12,6 %) их новорожденных диагностирована гипотрофия I ст. У нелечившихся женщин 16,7 % беременностей закончились самопроизвольным выкидышем; из 20 живорожденных детей 25 % умерли в раннем неонатальном периоде, 40 % детей родились с гипотрофией (р=0,0259); уровень перинатальных потерь – 35 %.

Заключение. Тестированием женщин с привычной потерей плода коагуляционной пробой РТТ ВА обнаруживается с частотой 49,6 %. ВА-позитивные женщины в прошлом потеряли 68,5 % беременностей. ВА у беременной с ПЭ в анамнезе является статистически и клинически значимым фактором высокого риска развития ПЭ, относительный риск – 4,5.

Ключевые слова: волчаночный антикоагулянт, коагуляционные пробы, привычный выкидыш, преэклампсия, исходы беременности.

 

Литература

  1. Dudley Antiphospholipid syndrome: A model for autoimmune pregnancy loss. Infert. Reprod. Med. Clin. North Am. 1991; 2: 149–155.
  2. Scott J.R., Rote N.S., Branch D.W. Immunologic aspects of recurrent abortion and fetal death. Obstet. Gynecol. 1987; 70: 645–656.
  3. Lockshin M., Kim M., Laskin C.A., Guerra M. Prediction of adverse pregnancy outcome by the presence of lupus anticoagulant, but not anticardiolipin antibody, in patients with antiphospholipid antibodies. Arthritis Rheumat. 2012; 64 (7): 2311–2318.
  4. Khamashta M.A. Antiphospholipid (Hughes) syndrome. Brit. Med. J. 1997; 314: 244.
  5. Hughes G.R.V. Autoantibodies in lupus and its variants: experience of 1000 patients. Brit. Med. J. 1984; 289: 339–342.
  6. Cunningham F.G., Leveno K.J., Bloom S.L. (eds). Williams Obstetrics. 22-nd. N.I. – Toronto, McGraw-Hill; 2005.
  7. Tate G., Scott J. Detection of lupus anticoagulant in stored serum. Lancet. 1984; 2: 587.
  8. Zwahr C., Räte K., Brietzke W. Letaler Ausgang bei lupus erythematosus viscerale und Gravidität. Zbl. Gynäkol. 1983; 105: 300–307.
  9. Qamar T., Levy R.A, Samaritano L. Characteristics of high-titer Ig G antiphospholipid antibody in systemic lupus erythematosus patients with and without fetal death. Arthritis Rheumat. 1990; 33: 501–504.
  10. Buyon J.P., Kim M.Y., Guerra M.M., Laskin C.A., Petri M. Predictors of Pregnancy Outcomes in Patients With Lupus: A Cohort Study. Ann. Intern. Med. 2015; 163 (3): 153–163.
  11. Blomjous B., Abheiden C., Kroese S., van Laar J. Pregnancy meets rheumatic patients. OP0310 Pregnancy outcome in women with systemic lupus erythematosus, a multicenter cohort-study. Obstet. Gynecol. Suppl. 2: Ann. European Congress of Rheumatology. 2017; 76: 14–17.
  12. Mankee A., Petri M., Magder L. Lupus anticoagulant, disease activity and low complement in the first timester are predictive of pregnancy loss. Lupus. 2017; 2 (1): 1–5.
  13. Galli M., Reber G., de Moerloose P., de Groot P.G. Invitation to a debate on the serological criteria that define the antiphospholipid syndrome. J. Thromb. Haemost. 2008; 6: 399–401.
  14. Степанова Р. Беременность и аутоиммунная патология. Lap Lambert. Saarbrucken; 2013. 147.
  15. Branch D.W., Khamashta M.A. Antiphospholipid syndrome: obstetric diagnosis, management and controversies. Obstet. Gynecol. 2003; 101: 1333–1344.
  16. Derksen R. Systemic Lupus Erythematosus and the Antiphospholipid Syndrome. Ann. Rheumat. Dis. 2017; 73: SP0087.
  17. Miyaskis S., Lockshin M.D., Atsumi T. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J. Thromb. Haemost. 2006; 4 (2): 295–306.
  18. Lockwood C.J., Romero R., Feinberg R.F. The prevalence and biologic signiticance of lupus anticoagulant and anticardiolipin antibodies in general obstetric population. Am. J. Obstet. Gynecol. 1989; 161: 369–373.
  19. Pattison N.S., Chamley L.W., Birdsall M. Does aspirin have a role in improving pregnancy outcome for women with the antiphospholipid syndrome? Am. J. Obstet. Gynecol. 2000; 183: 1008–1012.
  20. Woif de F., Carreras L.O., Moerman P. Decidual vasculopathy and extensive placental infarction in a patient with repeated thromboembolic accident, recurrent fetal loss and a lupus anticoagulant. Am. J. Gynecol. 1982; 142: 829–834.
  21. Sheridan-Pereira M., Porreco R.P., Hays T. Neonatal aortic thrombosis associated with the lupus anticoagulant. Obstet. Gynecol. 1988; 71: 1016–1017.
  22. Косова А.С., Степанова Р.Н. Современные подходы к прогнозированию и профилактике преэклампсии. Орел; 2016. 101.
  23. Foska A.F., Valenti O., Hysteni E., Giorgio E. Antiphospholipid Syndrome during pregnancy: the state of the art. J. Prenat. Med. 2011; 5 (2): 41–53.
  24. Simchen M.J., Dulitzki M., Rofe G. High positive antibody titers and adverse pregnancy outcome in women with antiphospholipid syndrome. Acta Obstet. Gynecol. Scand. 2011; 90 (12): 1428–1433.
  25. Branch D.W., Scott J.R., Kochenour N.K. Obstetric complications associated with the lupus anticoagulant. N. England J. Med. 1985; 313: 1322–1326.
  26. Gregorini G., Setti G., Remuzzi G. Recurrent abortion with lupus anticoagulant: a common final pathway for two different diseases? Brit. J. Obstet Gynecol. 1986; 93: 194–196.
  27. Beaufils M., Dousimini R., Usan S. Prevention of preeclampsia by early antiplatelet therapy. Lancet. 1985; 1: 840–842.
  28. Sibai B.M., Caraties S.N., Trom E. Prevention of preeclampsia with low-dose aspirin in healthy, multiparous pregnant women. N. Engl. J. Med. 1993; 329: 1213–1318.

 

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DOI: 10.23648/UMBJ.2017.28.8742

LUPUS ANTICOAGULANT AS A PREDICTOR OF ADVERSE PREGNANCY OUTCOMES

 

R.N. Stepanova, A.S. Kosova

Oryol State University named after I.S. Turgenev, Oryol, Russia

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In recent years, the influence of autoimmune pathology on fetal loss and other pregnancy complications has been widely discussed. Lupus anticoagulant (LA), an immunoglobulin that binds to phospholipids and proteins associated with the cell membrane is said to be responsible for such complications.

The purpose of the study was to identify LA autoimmune disorders in pregnant women, to determine its influence in predicting adverse pregnancy outcomes, to evaluate the prophylactic efficacy of acetylsalicylic acid and dipyridamole antiplatelet doses, which had been prescribed for LA-positive pregnant women.

Material and Methods. The high risk group included 125 women with adverse pregnancy outcome hospitalized with a threatened miscarriage. Preeclampsia, as well as 2–8 early abortions, was peculiar to obstetric history of such patients. All women were tested according to clinical classification of systemic lupus erythematosis (American College of Rheumatology). LA in the venous blood of patients was determined by a coagulation test with diluted tissue thromboplastin (DTT). LA-positive women took acetylsalicylic acid (125 mg/day) and dipyridamole (150 mg/day).

Results. According to DTT test, 62 (49.6 %) patients were LA-positive. In 8 (7.8 %) cases severe preeclampsia developed in pregnant women, in 6 cases it was found in LA-positve women. Preventive medication was accepted by 24 LA-positive women. Their pregnancies ended in term births, 3 newborns (12.6 %) demonstrated hypotrophy, stage 1. In untreated women, 16.7 % of pregnancies ended in spontaneous miscarriages; among 20 life-birth infants 25 % died in the early neonatal period; 40 % of babies were born with hypotrophy (p=0.0259); the level of perinatal losses was 35 %.

Conclusion. LA was detected in 49.6 % if women with repeated pregnancy loss were tested using coagulation probe DTT. LA-positive women had 68.5 % miscarriages in the past. LA in pregnant preeclamptic women is a statistically and clinically significant high risk factor, which can lead to further preeclampsia development, relative risk is 4.5.

Keywords: lupus anticoagulant, coagulation tests, repeated miscarriage, preeclampsia, pregnancy outcomes.

 

Referens

  1. Dudley D.J., Branch W. Antiphospholipid syndrome: A model for autoimmune pregnancy loss. Infert Reprod. Med. Clin. North Am. 1991; 2: 149–155.
  2. Scott J.R., Rote N.S., Branch D.W. Immunologic aspects of recurrent abortion and fetal death. Obstet. Gynecol. 1987; 70: 645–656.
  3. Lockshin M., Kim M., Laskin C.A., Guerra M. Prediction of adipose inhibitory antibodies, antiphospholipid antibodies. Arthritis Rheumat. 2012; 64 (7): 2311–2318.
  4. Khamashta M.A. Antiphospholipid (Hughes) syndrome. Brit. Med.1997; 314: 244.
  5. Hughes G.R.V. Autoantibodies in lupus and its variants: experience of 1000 patients. Brit. Med. J. 1984; 289: 339–342.
  6. Cunningham F.G., Leveno K.J., Bloom S.L., eds. Williams Obstetrics, 22-nd. N. I. – Toronto, McGraw-Hill, 2005.
  7. Tate G., Scott J. Detection of lupus anticoagulant in stored serum. Lancet. 1984; 2: 587.
  8. Zwahr C., Räte K., Brietzke W. Letaler Ausgang bei lupus erythematosus viscerale und Gravidität. Zbl. Gynäkol. 1983; 105: 300–307.
  9. Qamar T., Levy R.A., Samaritano L. Characteristics of high-titer Ig G antiphospholipid antibody in systemic lupus erythematosus patients with and without fetal death. Arthritis Rheumat. 1990; 33: 501–504.
  10. Buyon J.P., Kim M.Y., Guerra M.M., Laskin C.A., Petri M. Predictors of Pregnancy Outcomes in Patients With Lupus: A Cohort Study. Ann. Intern. Med. 2015; 163 (3): 153–163.
  11. Blomjous B., Abheiden C., Kroese S., van Laar J. Pregnancy meets rheumatic patients. OP0310 Pregnancy outcome in women with systemic lupus erythematosus, a multicenter cohort-study. Obstet. Gynecol. Suppl. 2: Ann. European Congress of Rheumatology. 2017; 76: 14–17.
  12. Mankee A., Petri M., Magder L. Lupus anticoagulant, disease activity and low complementary in the first trimester are predictive of pregnancy loss. Lupus. 2017; 2 (1): 1–5.
  13. Galli M., Reber G., de Moerloose P., de Groot P.G. Invitation to a debate on the serological criteria that define the antiphospholipid syndrome. J. Thromb. Haemost. 2008; 6: 399–401.
  14. Stepanova R. Beremennost' i autoimmunnaya patologiya [Pregnancy and autoimmune pathology]. Lap Lambert. Saarbrucken; 2013. 147 (in Russian).
  15. Branch D.W., Khamashta M.A. Antiphospholipid syndrome: obstetric diagnosis, management and controversies. Obstet. Gynecol. 2003; 101: 1333–1344.
  16. Derksen R. Systemic Lupus Erythematosus and the Antiphospholipid Syndrome. Ann. Rheumat. Dis. 2017; 73: SP0087.
  17. Miyaskis S., Lockshin M.D., Atsumi T. International consensus statement on definite antiphospholipid syndrome (APS). J. Thromb. Haemost. 2006; 4 (2): 295–306.
  18. Lockwood C.J., Romero R., Feinberg R.F. The prevalence and biologic significance of lupus anticoagulant and anticardiolipin antibodies in general obstetric population. Am. J. Obstet. Gynecol. 1989; 161: 369–373.
  19. Pattison N.S., Chamley L.W., Birdsall M. Does aspirin have an antiphospholipid syndrome? Am. J. Obstet. Gynecol. 2000; 183: 1008–1012.
  20. Woif de F., Carreras L.O., Moerman P. Decidual vasculopathy and extensive placental infarction in a patient with repeated thromboembolic accident, recurrent fetal loss and a lupus anticoagulant. Am. J. Gynecol. 1982; 142: 829–834.
  21. Sheridan-Pereira M., Porreco R.P., Hays T. Neonatal aortic thrombosis associated with the lupus anticoagulant. Obstet. Gynecol. 1988; 71: 1016–1017.
  22. Kosova A.S., Stepanova R.N. Sovremennye podkhody k prognozirovaniyu i profilaktike preeklampsii [Modern approaches to pregnancy and preeclampsia prevention]. Orel; 2016. 101 (in Russian).
  23. Foska A.F., Valenti O., Hysteni E., Giorgio E. Antiphospholipid Syndrome during pregnancy: the state of the art. J. Prenat. Med. 2011; 5 (2): 41–53.
  24. Simchen M.J., Dulitzki M., Rofe G. High positive antibody titers and adverse pregnancy outcome in women with antiphospholipid syndrome. Acta Obstet. Gynecol. Scand. 2011; 90 (12): 1428–1433.
  25. Branch D.W., Scott J.R., Kochenour N.K. Obstetric complications associated with the lupus anticoagulant. N. England J. Med. 1985; 313: 1322–1326.
  26. Gregorini G., Setti G., Remuzzi G. Recurrent abortion with lupus anticoagulant: a common final pathway for two different diseases? Brit. J. Obstet Gynecol. 1986; 93: 194–196.
  27. Beaufils M., Dousimini R., Usan S. Prevention of pre-eclampsia by early antiplatelet therapy. Lancet. 1985; 1: 840–842.
  28. Sibai B.M., Caraties S.N., Trom E. Prevention of preeclampsia with low-dose aspirin in healthy, multiparous pregnant women. N. Engl. J. Med. 1993; 329: 1213–1318.