Obstetric antiphospholipid syndrome

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

• 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
• 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
• 3 Schreiber K, Hunt BJ. Pregnancy and antiphospholipid syndrome. Semin Thromb Hemost. 2016; 42 (07) 780-788
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 12 Czwalinna A, Bergmann F. Prevention of pregnancy complications in antiphospholipid syndrome. Hamostaseologie. 2020; 40 (02) 174-183
• 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
• 14 Farquharson RG, Quenby S, Greaves M. Antiphospholipid syndrome in pregnancy: a randomized, controlled trial of treatment. Obstet Gynecol. 2002; 100 (03) 408-413
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 29 Silver RM. Catastrophic antiphospholipid syndrome and pregnancy. Semin Perinatol. 2018; 42 (01) 26-32
• 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
• 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
• 32 Unlu O, Erkan D. Catastrophic antiphospholipid syndrome: candidate therapies for a potentially lethal disease. Annu Rev Med. 2017; 68: 287-296