Persistence of antiphospholipid antibodies, features of pregnancy management

Clinical case

Authors

  • L.V. Kalugina SI “Ukrainian Center of Motherhood and Childhood of the NAMS of Ukraine”; SSI “Center for Innovative Medical Technologies of the NAS of Ukraine”, Kyiv , Ukraine https://orcid.org/0000-0003-2263-6627
  • I.O. Rodionova Educational and Scientific Center “Institute of Biology and Medicine”, Taras Shevchenko National University of Kyiv, Kyiv, Ukraine https://orcid.org/0000-0002-7893-8563
  • R.O. Mnevets Educational and Scientific Center “Institute of Biology and Medicine”, Taras Shevchenko National University of Kyiv; SI “Ukrainian Center of Motherhood and Childhood of the NAMS of Ukraine”, Kyiv, Ukraine https://orcid.org/0000-0001-9614-5762
  • T.I. Yusko SI “Ukrainian Center of Motherhood and Childhood of the NAMS of Ukraine”, Kyiv, Ukraine https://orcid.org/0000-0001-8516-6007
  • Y.I. Shuldiakova Educational and Scientific Center “Institute of Biology and Medicine”, Taras Shevchenko National University of Kyiv, Kyiv, Ukraine https://orcid.org/0009-0000-8105-1253

DOI:

https://doi.org/10.18370/2309-4117.2024.75.25-31

Keywords:

antiphospholipid syndrome, habitual miscarriage, recurrent miscarriage, systemic lupus erythematosus, clinical case

Abstract

Since antiphospholipid syndrome (APS) is a rare condition, it is often overlooked by clinicians. At the same time, APS is one of the causes of serious obstetric complications, including early pregnancy loss and preterm birth.
This clinical case describes the course of pregnancy by trimesters, labor, and postpartum period in a woman with systemic lupus erythematosus associated with APS, highlighting the management of pregnancy, labor, and postpartum care.
A 31-year-old woman was hospitalized at 4 weeks of pregnancy with a threatened miscarriage. This was her third pregnancy. The first and second pregnancies ended in early miscarriage. She has a family history of thrombosis: her father died from pulmonary artery thrombembolism at 49 years old, paternal relatives had thrombosis, and her maternal grandfather died from a stroke. The patient’s personal medical history is not complicated by thrombosis.
After excluding inherited thrombophilia, clinical and laboratory tests revealed the antiphospholipid antibodies (anti-β2-glycoprotein 1, anticardiolipin, lupus anticoagulant) and an elevated titer of antinuclear antibodies (ENA screening, anti-double-stranded DNA antibodies).
The patient was given combined antithrombotic therapy with aspirin and enoxaparin, combined with hydroxychloroquine. At 37 weeks, woman delivered a baby per vias naturalis without any complications during labor or the postpartum period.
Conclusions. Considering that APS is a common cause of pregnancy loss, this pathology requires proper attention from clinicians. The diagnosis and management of this thrombophilia are further complicated by the lack of an accepted standard for the care of such patients in Ukraine. Additionally, the existing APS criteria do not cover all patients who face difficulties in carrying a pregnancy due to the presence of antiphospholipid antibodies. This creates difficulties in recognizing these women, leaving them without appropriate treatment.

Author Biographies

L.V. Kalugina, SI “Ukrainian Center of Motherhood and Childhood of the NAMS of Ukraine”; SSI “Center for Innovative Medical Technologies of the NAS of Ukraine”, Kyiv

MD, professor, leading researcher, Endocrine Gynecology Department;
chief researcher,  Department of Reproductive Health

I.O. Rodionova, Educational and Scientific Center “Institute of Biology and Medicine”, Taras Shevchenko National University of Kyiv, Kyiv

PhD, associate professor, Department of Internal Medicine

R.O. Mnevets, Educational and Scientific Center “Institute of Biology and Medicine”, Taras Shevchenko National University of Kyiv; SI “Ukrainian Center of Motherhood and Childhood of the NAMS of Ukraine”, Kyiv

Assistant, Department of Pediatrics, Obstetrics and Gynecology;
Intern

T.I. Yusko, SI “Ukrainian Center of Motherhood and Childhood of the NAMS of Ukraine”, Kyiv

Junior researcher, Endocrine Gynecology Department

Y.I. Shuldiakova, Educational and Scientific Center “Institute of Biology and Medicine”, Taras Shevchenko National University of Kyiv, Kyiv

Student

References

  1. Petri М. Antiphospholipid Syndrome. Translational Research. 2020; Nov 225:70–81. DOI: 10.1016/j.trsl.2020.04.006
  2. Regan L, Rai R, Saravelos S, et al. Recurrent Miscarriage Green-top Guideline No. 17. BJOG. 2023 Nov;130(12):e9–e39. DOI: 10.1111/1471-0528.17515
  3. Lockwood CJ, Lockshin MD. Antiphospholipid syndrome: Obstetric implications and management in pregnancy [Internet]. UpToDate. 2024 15 May. Available from: https://www.uptodate.com/contents/antiphospholipid-syndrome-obstetric-implications-and-management-in-pregnancy?topicRef=4682&source=see_link
  4. Lee EE, Jun JK, Leе EB. Management of Women with Antiphospholipid Antibodies or Antiphospholipid Syndrome during Pregnancy. Journal of Korean Medical Science. 2021; Jan 25; 36(4): e24. DOI: 10.3346/jkms.2021.36.e24
  5. Andreoli L, Chighizola CB, Banzato A, et al. Estimated frequency of antiphospholipid antibodies in patients with pregnancy morbidity, stroke, myocardial infarction, and deep vein thrombosis: a critical review of the literature. Arthritis Care and Research. 2013 Nov;65(11):1869–73. DOI: 10.1002/acr.22066Chaturvedi
  6. Daya S, Stephenson MD. Frequency of factors associated with habitual abortion in 197 couples. Fertility and Sterility. Jul;66(1):24–9. DOI: 10.1016/S0015-0282(16)58382-4
  7. Erkan D, Zuily S. Clinical manifestations of antiphospholipid syndrome. [Internet]. UpToDate. 2024 04 Mar. Available from: https://www.uptodate.com/contents/clinical-manifestations-of-antiphospholipid-syndrome?topicRef=4682&source=see_link
  8. Radin M, Sciascia S, Bazzan M, et al. Antiphospholipid Syndrome Is Still a Rare Disease-Estimated Prevalence in the Piedmont and Aosta Valley Regions of Northwest Italy: Comment on the Article by Duarte-García et al. Arthritis & Rheumatology. 2020 Oct;72(10):1774–6. DOI: 10.1002/art.41401
  9. Dabit JY, Valenzuela-Almada MO, Vallejo-Ramos S, et al. Epidemiology of Antiphospholipid Syndrome in the General Population. 2021; 23(12): 85. DOI: 10.1007/s11926-021-01038-2
  10. Walter IJ, Haneveld MJK, Lely AT. Pregnancy outcome predictors in antiphospholipid syndrome: A systematic review and meta-analysis. Autoimmunity Reviews. 2021;20(10):102901. DOI: 10.1016/j.autrev.2021.102901
  11. Duarte-García A, Pham MM, Crowson CS, et al. The Epidemiology of Antiphospholipid Syndrome: A Population-Based Study. Arthritis and Rheumatology. 2019 Sep;71(9):1545–52. DOI: 10.1002/art.40901
  12. Hwang JJ, Shin SH, Kim YJ, et al. Epidemiology of Antiphospholipid Syndrome in Korea: a Nationwide Population-based Study. Journal of Korean Medical Science. 2020 Feb 10;35(5):e35. DOI: 10.3346/jkms.2020.35.e35
  13. Silver RM, Parker CB, Reddy UM, et al. Antiphospholipid antibodies in stillbirth. Obstetrics & Gynecology. 2013 Sep;122(3):641–57. DOI: 10.1097/AOG.0b013e3182a1060e
  14. Foddai SG, Radin M, Cecchi I, et al. The prevalence of antiphospholipid antibodies in women with late pregnancy complications and low-risk for chromosomal abnormalities. Journal Thrombosis and Haemostasis. 2020 Nov;18(11):2921–8. DOI: 10.1111/jth.15053
  15. Gibbins KJ, Tebo AE, Nielsen SK, et al. Antiphospholipid antibodies in women with severe preeclampsia and placental insufficiency: a case-control study. Sage Journals. 2018 Oct;27(12):1903–10. DOI: 10.1177/0961203318787035
  16. Gropp K, Weber N, Reuter M, et al. β₂-glycoprotein I, the major target in antiphospholipid syndrome, is a special human complement regulator. Blood. 2011 Sep 8;118(10):2774–83. DOI: 10.1182/blood-2011-02-339564
  17. Arreola-Diaz R, Majluf-Cruz A, Sanchez-Torres LE, et al. The Pathophysiology of The Antiphospholipid Syndrome: A Perspective From The Blood Coagulation System. Sage Journals. 2022 Jan–Dec:28:10760296221088576. DOI: 10.1177/10760296221088576.
  18. Butt A, Erkan D, Lee AI. COVID-19 and antiphospholipid antibodies. Best Practice & Research Clinical Haematology. 2022 Sep; 35(3): 101402. DOI: 10.1016/j.beha.2022.101402
  19. Xiao M, Zhang Y, Zhang S, et al. Antiphospholipid Antibodies in Critically Ill Patients With COVID-19. Arthritis and Rheumatology. 2020 Dec;72(12):1998–2004. DOI: 10.1002/art.41425
  20. Gazzaruso C, Mariani G, Ravetto C, et al. Lupus anticoagulant and mortality in patients hospitalized for COVID-19. Journal of Thrombosis and Thrombolysis. 2021 Jul;52(1):85–91. DOI: 10.1007/s11239-020-02335-w
  21. Serrano M, Espinosa G, Lalueza A, et al. Beta-2-Glycoprotein-I Deficiency Could Precipitate an Antiphospholipid Syndrome-like Prothrombotic Situation in Patients With Coronavirus Disease 2019. ACR Open Rheumatology. 2021 Apr;3(4):267–76. DOI: 10.1002/acr2.11245
  22. Erkan D, Ortel TL. Antiphospholipid syndrome: Diagnosis. [Internet] UpToDate. 2024 27 Sep. Available from: https://www.uptodate.com/contents/antiphospholipid-syndrome-diagnosis
  23. Golovach IU, Chipko TM, Lazorenko OO. Criterion and non-criterion antiphospholipid syndrome: conceptual issues of diagnosis. Ukrainian Journal of Rheumatology. 2021; 85(3):26-31. DOI: 10.32471/rheumatology.2707-6970.85.16436
  24. Chaturvedi S, Knight JS. Antiphospholipid syndrome: Pathogenesis. [Internet] UpToDate. 2024 26 Jul. Available from: https://www.uptodate.com/contents/antiphospholipid-syndrome-pathogenesis
  25. Zhang W, Gao F, Lu D, et al. Anti-β2 glycoprotein I antibodies in complex with β2 glycoprotein I induce platelet activation via two receptors: apolipoprotein E receptor 2’ and glycoprotein I bα. Frontiers of Medicine. 2016 Mar;10(1):76–84. DOI: 10.1007/s11684-015-0426-7
  26. Sule G, Kelley WJ, Gockman K, et al. Increased Adhesive Potential of Antiphospholipid Syndrome Neutrophils Mediated by β2 Integrin Mac-1. Arthritis and Rheumatology. 2020 Jan;72(1):114–24. DOI: 10.1002/art.41057
  27. Bang S, Jang MJ, Kim KH, et al. Prevention of venous thromboembolism, 2nd edition: Korean Society of Thrombosis and Hemostasis Evidence-based Clinical Practice Guidelines. 2014 Feb;29(2):164–71. DOI: 10.3346/jkms.2014.29.2.164
  28. Shehata H, Ali A, Silva-Edge M, et al. Thrombophilia screening in women with recurrent first trimester miscarriage: is it time to stop testing? - a cohort study and systematic review of the literature. BMJ Open. 2022 Jul 13;12(7):e059519. DOI: 10.1136/bmjopen-2021-059519
  29. Carrasco MF, Triana AM, GarcГ­a ICC, et al. Catastrophic antiphospholipid syndrome during pregnancy. European Journal of Obstetrics and Gynecology and Reproductive Biology. 2021 Sep; 264: 21–24. DOI: 10.1016/j.ejogrb.2021.07.002
  30. Erkan D, Ortel TL. Catastrophic antiphospholipid syndrome (CAPS). [Internet] UpToDate. 2024 05 Aug. Available from: https://www.uptodate. com/contents/catastrophic-antiphospholipid-syndrome-caps?topicRef=4682&source=see_link
  31. Hanouna G, Morel N, Le Thi Huong D, et al. Catastrophic antiphospholipid syndrome and pregnancy: an experience of 13 cases. Rheumatology. 2013 Sep;52(9):1635–41. DOI: 10.1093/rheumatology/ket167
  32. Moulinet T, Dufrost V, Clerc-Urmès I, et al. Risk of thrombosis, pregnancy morbidity or death in antiphospholipid antibodies positive patients with or without thrombocytopenia. European Journal of Internal Medicine. 2021 Feb:84:101–3. DOI: 10.1016/j.ejim.2020.10.011
  33. Pignatelli P, Ettorre E, Menichelli D, et al. Seronegative antiphospholipid syndrome: refining the value of “non-criteria” antibodies for diagnosis and clinical management. Haematologica. 2020 Mar; 105(3): 562–72. DOI: 10.3324/haematol.2019.221945
  34. Erkan D, Ortel TL. Antiphospholipid syndrome: Management. UpToDate. 2024 27 Sep. [Internet] Available from: https://www.uptodate.com/contents/antiphospholipid-syndrome-management
  35. Bauer KA, Lockwood CJ. Anticoagulation during pregnancy and postpartum: Selection and dosing. [Internet] UpToDate. 2024 07 Oct. Available from: https://www.uptodate.com/contents/anticoagulation-during-pregnancy-and-postpartum-selection-and-dosing
  36. Bates SM, Rajasekhar A, Middeldorp S, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: venous thromboembolism in the context of pregnancy. Blood Advances. 2018 Nov 27;2(22):3317–59. DOI: 10.1182/bloodadvances.2018024802
  37. Beyer-Westendorf J, Michalski F, Tittl L, et al. Pregnancy outcome in patients exposed to direct oral anticoagulants – and the challenge of event reporting. Thrombosis and Haemostasis. 2016 Sep 27;116(4):651–8. DOI: 10.1160/TH16-04-0305
  38. Latino JO, Udry S, Aranda FM, et al. Pregnancy failure in patients with obstetric antiphospholipid syndrome with conventional treatment: the influence of a triple positive antibody profile. Sage Journals. 2017 Aug;26(9):983–88. DOI: 10.1177/0961203317692432
  39. Latino JO, Udry S, Aranda F, et al. Risk factors for early severe preeclampsia in obstetric antiphospholipid syndrome with conventional treatment. The impact of hydroxychloroquine. Sage Journals. 2020 Nov;29(13):1736–42. DOI: 10.1177/0961203320952850
  40. Ruffatti A, Tonello M, Hoxha A, et al. Effect of Additional Treatments Combined with Conventional Therapies in Pregnant Patients with High-Risk Antiphospholipid Syndrome: A Multicentre Study. Thrombosis and Haemostasis. 2018 Apr;118(4):639–46. DOI: 10.1055/s-0038-1632388

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Published

2024-12-31

How to Cite

Kalugina, L., Rodionova, I., Mnevets, R., Yusko, T., & Shuldiakova, Y. (2024). Persistence of antiphospholipid antibodies, features of pregnancy management : Clinical case. REPRODUCTIVE ENDOCRINOLOGY, (75), 25–31. https://doi.org/10.18370/2309-4117.2024.75.25-31

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No. 75 (2024)

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