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CC BY 4.0 · Rev Bras Ginecol Obstet 2021; 43(06): 495-501
DOI: 10.1055/s-0041-1732382
Febrasgo Position Statement

Obstetric antiphospholipid syndrome

Number 6 - June 2021
Venina Isabel Poço Viana Leme de Barros 
1   Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil
,
Ana Maria Kondo Igai 
2   Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil
,
André Luiz Malavasi Longo de Oliveira 
3   Hospital Pérola Byington, São Paulo, SP, Brazil
,
Marcelo Melzer Teruchkin 
4   Hospital Moinhos de Vento, Porto Alegre, Rio Grande do Sul, Brazil
,
Fernanda Andrade Orsi 
5   Faculdade de Ciências Médicas da Universidade de Campinas, Campinas, SP, Brazil
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Key points

  • Antiphospholipid syndrome (APS) is an acquired thrombophilia often associated with adverse obstetric outcomes.

  • APS severity depends on the type and complexity of the antibodies. Triple positivity for antiphospholipid antibodies and high antibody titers are commonly associated with a more severe disease.

  • The antiphospholipid antibodies described for the diagnosis of the syndrome are: IGG and IGM anticardiolipin, lupus anticoagulant and IGG and IgM antibeta2 GPI.

  • The occurrence of venous and/or arterial thrombosis is part of the clinical condition.

  • Treatment for APS in pregnancy consists in the use of low molecular weight heparin (LMWH) and low dose aspirin. The dose for anticoagulation depends on the presence or absence of previous thrombosis and the type of obstetric morbidity.

  • Patients refractory to anticoagulation treatment may need additional therapies (hydroxychloroquine, prednisone and/or intravenous immunoglobulin).

The National Specialty Commission for Venous Thromboembolisms of the Brazilian Federation of Gynecology and Obstetrics Associations (FEBRASGO) endorses to this document. The content production is based on scientific studies on a thematic proposal and the findings presented contribute to clinical practice.




Publication History

Article published online:
27 July 2021

© 2021. Federação Brasileira de Ginecologia e Obstetrícia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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  • References

  • 1 Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R. et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006; 4 (02) 295-306 DOI: 10.1111/j.1538-7836.2006.01753.x.
    CrossrefPubMedGoogle Scholar
  • 2 Cervera R, Piette JC, Font J, Khamashta MA, Shoenfeld Y, Camps MT. et al. Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis Rheum. 2002; 46 (04) 1019-1027 DOI: 10.1002/art.10187.
    CrossrefPubMedGoogle Scholar
  • 3 Schreiber K, Hunt BJ. Pregnancy and antiphospholipid syndrome. Semin Thromb Hemost. 2016; 42 (07) 780-788 DOI: 10.1055/s-0036-1592336.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 4 Meroni PL, Borghi MO, Grossi C, Chighizola CB, Durigutto P, Tedesco F. Obstetric and vascular antiphospholipid syndrome: same antibodies but different diseases?. Nat Rev Rheumatol. 2018; 14 (07) 433-440 DOI: 10.1038/s41584-018-0032-6.
    CrossrefPubMedGoogle Scholar
  • 5 Cervera R, Serrano R, Pons-Estel GJ, Ceberio-Hualde L, Shoenfeld Y, de Ramón E. et al. Morbidity and mortality in the antiphospholipid syndrome during a 10-year period: a multicentre prospective study of 1000 patients. Ann Rheum Dis. 2015; 74 (06) 1011-1018 DOI: 10.1136/annrheumdis-2013-204838.
    CrossrefPubMedGoogle Scholar
  • 6 Pengo V, Biasiolo A, Pegoraro C, Cucchini U, Noventa F, Iliceto S. Antibody profiles for the diagnosis of antiphospholipid syndrome. Thromb Haemost. 2005; 93 (06) 1147-1152 DOI: 10.1160/TH04-12-0839.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 7 Tektonidou MG, Andreoli L, Limper M, Amoura Z, Cervera R, Costedoat-Chalumeau N. et al. EULAR recommendations for the management of antiphospholipid syndrome in adults. Ann Rheum Dis. 2019; 78 (10) 1296-1304 DOI: 10.1136/annrheumdis-2019-215213.
    CrossrefPubMedGoogle Scholar
  • 8 Lynch A, Marlar R, Murphy J, Davila G, Santos M, Rutledge J. et al. Antiphospholipid antibodies in predicting adverse pregnancy outcome. A prospective study. Ann Intern Med. 1994; 120 (06) 470-475 DOI: 10.7326/0003-4819-120-6-199403150-00004.
    CrossrefPubMedGoogle Scholar
  • 9 Abou-Nassar K, Carrier M, Ramsay T, Rodger MA. The association between antiphospholipid antibodies and placenta mediated complications: a systematic review and meta-analysis. Thromb Res. 2011; 128 (01) 77-85 DOI: 10.1016/j.thromres.2011.02.006.
    CrossrefPubMedGoogle Scholar
  • 10 Cowchock S, Reece EA. Do low-risk pregnant women with antiphospholipid antibodies need to be treated? Organizing Group of the Antiphospholipid Antibody Treatment Trial. Am J Obstet Gynecol. 1997; 176 (05) 1099-1100 DOI: 10.1016/s0002-9378(97)70409-5.
    CrossrefPubMedGoogle Scholar
  • 11 Del Ross T, Ruffatti A, Visentin MS, Tonello M, Calligaro A, Favaro M. et al. Treatment of 139 pregnancies in antiphospholipid-positive women not fulfilling criteria for antiphospholipid syndrome: a retrospective study. J Rheumatol. 2013; 40 (04) 425-429 DOI: 10.3899/jrheum.120576.
    CrossrefPubMedGoogle Scholar
  • 12 Czwalinna A, Bergmann F. Prevention of pregnancy complications in antiphospholipid syndrome. Hamostaseologie. 2020; 40 (02) 174-183 DOI: 10.1055/a-1113-0689.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 13 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): 253-257 DOI: 10.1136/bmj.314.7076.253.
    CrossrefPubMedGoogle Scholar
  • 14 Farquharson RG, Quenby S, Greaves M. Antiphospholipid syndrome in pregnancy: a randomized, controlled trial of treatment. Obstet Gynecol. 2002; 100 (03) 408-413 DOI: 10.1016/s0029-7844(02)02165-8.
    CrossrefPubMedGoogle Scholar
  • 15 Cohn DM, Goddijn M, Middeldorp S, Korevaar JC, Dawood F, Farquharson RG. Recurrent miscarriage and antiphospholipid antibodies: prognosis of subsequent pregnancy. J Thromb Haemost. 2010; 8 (10) 2208-2213 DOI: 10.1111/j.1538-7836.2010.04015.x.
    CrossrefPubMedGoogle Scholar
  • 16 Mak A, Cheung MW, Cheak AA, Ho RC. 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. 2010; 49 (02) 281-288 DOI: 10.1093/rheumatology/kep373.
    CrossrefPubMedGoogle Scholar
  • 17 van Hoorn ME, Hague WM, van Pampus MG, Bezemer D, de Vries JI. FRUIT Investigators. Low-molecular-weight heparin and aspirin in the prevention of recurrent early-onset pre-eclampsia in women with antiphospholipid antibodies: the FRUIT-RCT. Eur J Obstet Gynecol Reprod Biol. 2016; 197: 168-173 DOI: 10.1016/j.ejogrb.2015.12.011.
    CrossrefPubMedGoogle Scholar
  • 18 Belizna C, Pregnolato F, Abad S, Alijotas-Reig J, Amital H, Amoura Z. et al. HIBISCUS: Hydroxychloroquine for the secondary prevention of thrombotic and obstetrical events in primary antiphospholipid syndrome. Autoimmun Rev. 2018; 17 (12) 1153-1168 DOI: 10.1016/j.autrev.2018.05.012.
    CrossrefPubMedGoogle Scholar
  • 19 Ruffatti A, Tonello M, Visentin MS, Bontadi A, Hoxha A, De Carolis S. et al. Risk factors for pregnancy failure in patients with anti-phospholipid syndrome treated with conventional therapies: a multicentre, case-control study. Rheumatology. 2011; 50 (09) 1684-1689 DOI: 10.1093/rheumatology/ker139.
    CrossrefPubMedGoogle Scholar
  • 20 Fredi M, Andreoli L, Aggogeri E, Bettiga E, Lazzaroni MG, Le Guern V. et al. Risk factors for adverse maternal and fetal outcomes in women with confirmed aPL positivity: results from a multicenter study of 283 pregnancies. Front Immunol. 2018; 9: 864 DOI: 10.3389/fimmu.2018.00864.
    CrossrefPubMedGoogle Scholar
  • 21 Bramham K, Thomas M, Nelson-Piercy C, Khamashta M, Hunt BJ. First-trimester low-dose prednisolone in refractory antiphospholipid antibody-related pregnancy loss. Blood. 2011; 117 (25) 6948-6951 DOI: 10.1182/blood-2011-02-339234.
    CrossrefPubMedGoogle Scholar
  • 22 Tenti S, Cheleschi S, Guidelli GM, Galeazzi M, Fioravanti A. Intravenous immunoglobulins and antiphospholipid syndrome: how, when and why? A review of the literature. Autoimmun Rev. 2016; 15 (03) 226-235 DOI: 10.1016/j.autrev.2015.11.009.
    CrossrefPubMedGoogle Scholar
  • 23 Ruffatti A, Favaro M, Hoxha A, Zambon A, Marson P, Del Ross T. 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: 14-19 DOI: 10.1016/j.jri.2016.03.004.
    CrossrefPubMedGoogle Scholar
  • 24 El-Haieg DO, Zanati MF, El-Foual FM. Plasmapheresis and pregnancy outcome in patients with antiphospholipid syndrome. Int J Gynaecol Obstet. 2007; 99 (03) 236-241 DOI: 10.1016/j.ijgo.2007.05.045.
    CrossrefPubMedGoogle Scholar
  • 25 Mekinian A, Lazzaroni MG, Kuzenko A, Alijotas-Reig J, Ruffatti A, Levy P. et al. The efficacy of hydroxychloroquine for obstetrical outcome in anti-phospholipid syndrome: data from a European multicenter retrospective study. Autoimmun Rev. 2015; 14 (06) 498-502 DOI: 10.1016/j.autrev.2015.01.012.
    CrossrefPubMedGoogle Scholar
  • 26 Ruffatti A, Tonello M, Hoxha A, Sciascia S, Cuadrado MJ, Latino JO. et al. Effect of additional treatments combined with conventional therapies in pregnant patients with high-risk antiphospholipid syndrome: a multicentre study. Thromb Haemost. 2018; 118 (04) 639-646 DOI: 10.1055/s-0038-1632388.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 27 Schreiber K, Breen K, Cohen H, Jacobsen S, Middeldorp S, Pavord S. et al. HYdroxychloroquine to Improve Pregnancy Outcome in Women with AnTIphospholipid Antibodies (HYPATIA) protocol: a multinational randomized controlled trial of hydroxychloroquine versus placebo in addition to standard treatment in pregnant women with antiphospholipid syndrome or antibodies. Semin Thromb Hemost. 2017; 43 (06) 562-571 DOI: 10.1055/s-0037-1603359.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 28 de Jesús GR, Sciascia S, Andrade D, Barbhaiya M, Tektonidou M, Banzato A. et al. Factors associated with first thrombosis in patients presenting with obstetric antiphospholipid syndrome (APS) in the APS Alliance for Clinical Trials and International Networking Clinical Database and Repository: a retrospective study. BJOG. 2019; 126 (05) 656-661 DOI: 10.1111/1471-0528.15469.
    CrossrefPubMedGoogle Scholar
  • 29 Silver RM. Catastrophic antiphospholipid syndrome and pregnancy. Semin Perinatol. 2018; 42 (01) 26-32 DOI: 10.1053/j.semperi.2017.11.006.
    CrossrefPubMedGoogle Scholar
  • 30 Rodríguez-Pintó I, Moitinho M, Santacreu I, Shoenfeld Y, Erkan D, Espinosa G. et al. Catastrophic antiphospholipid syndrome (CAPS): descriptive analysis of 500 patients from the International CAPS Registry. Autoimmun Rev. 2016; 15 (12) 1120-1124 DOI: 10.1016/j.autrev.2016.09.010.
    CrossrefPubMedGoogle Scholar
  • 31 Berman H, Rodríguez-Pintó I, Cervera R, Morel N, Costedoat-Chalumeau N, Erkan D. et al. Rituximab use in the catastrophic antiphospholipid syndrome: descriptive analysis of the CAPS registry patients receiving rituximab. Autoimmune Rev. 2013; 12 (11) 1085-1090 DOI: 10.1016/j.autrev.2013.05.004.
    CrossrefPubMedGoogle Scholar
  • 32 Unlu O, Erkan D. Catastrophic antiphospholipid syndrome: candidate therapies for a potentially lethal disease. Annu Rev Med. 2017; 68: 287-296 DOI: 10.1146/annurev-med-042915-102529.
    CrossrefPubMedGoogle Scholar