Antiphospholipid syndrome (APS) is an autoimmune disease characterized by the presence of antiphospholipid antibodies, such as lupus anticoagulant, anticardiolipin antibodies and anti-β2-glycoprotein 1 antibodies. APS can present with a variety of clinical phenotypes, including thrombosis in the veins, arteries and microvasculature as well as obstetrical complications. The pathophysiological hallmark is thrombosis, but other factors such as complement activation might be important. Prevention of thrombotic manifestations associated with APS includes lifestyle changes and, in individuals at high risk, low-dose aspirin. Prevention and treatment of thrombotic events are dependent mainly on the use of vitamin K antagonists. Immunosuppression and anticomplement therapy have been used anecdotally but have not been adequately tested. Pregnancy morbidity includes unexplained recurrent early miscarriage, fetal death and late obstetrical manifestation such as pre-eclampsia, premature birth or fetal growth restriction associated with placental insufficiency. Current treatment to prevent obstetrical morbidity is based on low-dose aspirin and/or low-molecular-weight heparin and has improved pregnancy outcomes to achieve successful live birth in >70% of pregnancies. Although hydroxychloroquine and pravastatin might further improve pregnancy outcomes, prospective clinical trials are required to confirm these findings.
Subscribe to Journal
Get full journal access for 1 year
only $65.00 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Ruiz-Irastorza, G., Crowther, M., Branch, W. & Khamashta, M. A. Antiphospholipid syndrome. Lancet 376, 1498–1509 (2010).
Miyakis, S. et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J. Thromb. Haemost. 4, 295–306 (2006). This paper outlines the current APS classification criteria, commonly referred to as ‘Miyakis criteria’.
Ruiz-Irastorza, G. et al. Evidence-based recommendations for the prevention and long-term management of thrombosis in antiphospholipid antibody-positive patients: report of a task force at the 13th International Congress on antiphospholipid antibodies. Lupus 20, 206–218 (2011).
Radin, M. & Sciascia, S. Infodemiology of systemic lupus erythematous using Google Trends. Lupus 26, 886–889 (2017).
Tripodi, A. et al. Variability of cut-off values for the detection of lupus anticoagulants: results of an international multicenter multiplatform study. J. Thromb. Haemost. 15, 1180–1190 (2017).
Durcan, L. & Petri, M. Epidemiology of the Antiphospholipid Syndrome (Elsevier, 2016).
Rodriguez-Pinto, I. et al. Catastrophic antiphospholipid syndrome (CAPS): Descriptive analysis of 500 patients from the International CAPS Registry. Autoimmun. Rev. 15, 1120–1124 (2016).
Mehrani T. & Petri, M. in Handbook of Systemic Autoimmune Diseases Vol. 10 (eds Cervera, R., Reverter, J. C. & Khamashta, M. ) 13–34 (Elsevier, 2009).
Meroni, P. L. et al. Anti-beta 2 glycoprotein I antibodies in centenarians. Exp. Gerontol. 39, 1459–1465 (2004).
Andreoli, L. 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 Res. 65, 1869–1873 (2013).
Urbanus, R. T. et al. Antiphospholipid antibodies and risk of myocardial infarction and ischaemic stroke in young women in the RATIO study: a case-control study. Lancet Neurol. 8, 998–1005 (2009).
Martinez-Zamora, M. A. et al. Risk of thromboembolic events after recurrent spontaneous abortion in antiphospholipid syndrome: a case-control study. Ann. Rheum. Dis. 71, 61–66 (2012).
Gris, J. C. et al. Comparative incidence of a first thrombotic event in purely obstetric antiphospholipid syndrome with pregnancy loss: the NOH-APS observational study. Blood 119, 2624–2632 (2012).
Quenby, S., Farquharson, R. G., Dawood, F., Hughes, A. M. & Topping, J. Recurrent miscarriage and long-term thrombosis risk: a case-control study. Hum. Reprod. 20, 1729–1732 (2005).
Alijotas-Reig, J. et al. The European Registry on Obstetric Antiphospholipid Syndrome (EUROAPS): a survey of 247 consecutive cases. Autoimmun. Rev. 14, 387–395 (2015).
Abou-Nassar, K., Carrier, M., Ramsay, T. & Rodger, M. A. The association between antiphospholipid antibodies and placenta mediated complications: a systematic review and meta-analysis. Thromb. Res. 128, 77–85 (2011).
Silver, R. K. M. et al. Comparative trial of prednisone plus aspirin versus aspirin alone in the treatment of anticardiolipin antibody-positive obstetric patients. Am. J. Obstetr. Gynecol. 169, 1411–1417 (1993).
Page, J. M. et al. Diagnostic tests for evaluation of stillbirth: stillbirth collaborative research network. Obstet. Gynecol. 129, 699–706 (2017).
Tektonidou, M. G., Laskari, K., Panagiotakos, D. B. & Moutsopoulos, H. M. Risk factors for thrombosis and primary thrombosis prevention in patients with systemic lupus erythematosus with or without antiphospholipid antibodies. Arthritis Rheum. 61, 29–36 (2009).
Biggioggero, M. & Meroni, P. L. The geoepidemiology of the antiphospholipid antibody syndrome. Autoimmun. Rev. 9, A299–A304 (2010).
Shrivastava, A., Dwivedi, S., Aggarwal, A. & Misra, R. Anti-cardiolipin and anti-beta 2 glycoprotein I antibodies in Indian patients with systemic lupus erythematosus: association with the presence of seizures. Lupus 10, 45–50 (2001).
Mok, M. Y. C. et al. Antiphospholipid antibody profiles and their clinical associations in Chinese patients with systemic lupus erythematosus. J. Rheumatol. 32, 622–628 (2005).
Cruz-Tapias, P., Blank, M., Anaya, J. M. & Shoenfeld, Y. Infections and vaccines in the etiology of antiphospholipid syndrome. Curr. Opin. Rheumatol. 24, 389–393 (2012).
de Laat, B. et al. Immune responses against domain I of β2-glycoprotein I are driven by conformational changes: domain I of β2-glycoprotein I harbors a cryptic immunogenic epitope. Arthritis Rheum. 63, 3960–3968 (2011).
van Os, G. M. et al. Induction of anti-β2 -glycoprotein I autoantibodies in mice by protein H of Streptococcus pyogenes. J. Thromb. Haemost. 9, 2447–2456 (2011).
Pengo, V. et al. Incidence of a first thromboembolic event in asymptomatic carriers of high-risk antiphospholipid antibody profile: a multicenter prospective study. Blood 118, 4714–4718 (2011).
Exner, T., Barber, S., Kronenberg, H. & Rickard, K. A. Familial association of the lupus anticoagulant. Br. J. Haematol. 45, 89–96 (1980).
Matthey, F., Walshe, K., Mackie, I. J. & Machin, S. J. Familial occurrence of the antiphospholipid syndrome. J. Clin. Pathol. 42, 495–497 (1989).
Jolidon, R. M., Knecht, H., Humair, L. & de Torrente, A. Different clinical presentations of a lupus anticoagulant in the same family. Klin. Wochenschr. 69, 340–344 (1991).
Sebastiani, G. D., Iuliano, A., Cantarini, L. & Galeazzi, M. Genetic aspects of the antiphospholipid syndrome: an update. Autoimmun. Rev. 15, 433–439 (2016).
Cervera, R. S. et al. Morbidity and mortality in the antiphospholipid syndrome during a 10-year period: a multicentre prospective study of 1000 patients. Ann. Rheum. Dis. 74, 1011–1018 (2015).
Lijfering, W. M., Flinterman, L. E., Vandenbroucke, J. P., Rosendaal, F. R. & Cannegieter, S. C. Relationship between venous and arterial thrombosis: a review of the literature from a causal perspective. Semin. Thromb. Hemost. 37, 885–896 (2011).
de Groot, P. G., Urbanus, R. T. & Derksen, R. H. Pathophysiology of thrombotic APS: where do we stand? Lupus 21, 704–707 (2012).
Jankowski, M. et al. Thrombogenicity of β2-glycoprotein I-dependent antiphospholipid antibodies in a photochemically induced thrombosis model in the hamster. Blood 101, 157–162 (2003).
Romay-Penabad, Z. et al. Apolipoprotein E receptor 2 is involved in the thrombotic complications in a murine model of the antiphospholipid syndrome. Blood 117, 1408–1414 (2011).
Fischetti, F. et al. Thrombus formation induced by antibodies to β2-glycoprotein I is complement dependent and requires a priming factor. Blood 106, 2340–2346 (2005).
Pericleous, C. et al. Proof-of-concept study demonstrating the pathogenicity of affinity-purified IgG antibodies directed to domain I of β2-glycoprotein I in a mouse model of anti-phospholipid antibody-induced thrombosis. Rheumatology 54, 722–727 (2015).
Ioannou, Y. et al. In vivo inhibition of antiphospholipid antibody-induced pathogenicity utilizing the antigenic target peptide domain I of β2-glycoprotein I: proof of concept. J. Thromb. Haemost. 7, 833–842 (2009).
Agar, C., de Groot, P. G., Marquart, J. A. & Meijers, J. C. Evolutionary conservation of the lipopolysaccharide binding site of β2-glycoprotein I. Thromb. Haemost. 106, 1069–1075 (2011).
Vega-Ostertag, M., Liu, X., Kwan-Ki, H., Chen, P. & Pierangeli, S. A human monoclonal antiprothrombin antibody is thrombogenic in vivo and upregulates expression of tissue factor and E-selectin on endothelial cells. Br. J. Haematol. 135, 214–219 (2006).
Haj-Yahia, S. et al. Anti-prothrombin antibodies cause thrombosis in a novel qualitative ex-vivo animal model. Lupus 12, 364–369 (2003).
Manukyan, D. et al. Cofactor-independent human antiphospholipid antibodies induce venous thrombosis in mice. J. Thromb. Haemost. 14, 1011–1020 (2016).
Forastiero, R., Martinuzzo, M., de Larranaga, G., Vega-Ostertag, M. & Pierangeli, S. Anti-β2glycoprotein I antibodies from leprosy patients do not show thrombogenic effects in an in vivo animal model. J. Thromb. Haemost. 9, 859–861 (2011).
de Groot, P. G. & Urbanus, R. T. The significance of autoantibodies against β2-glycoprotein I. Blood 120, 266–274 (2012). This paper highlights the importance of anti-β2-glycoprotein 1 in APS.
Chaturvedi, S., Alluri, R. & McCrae, K. R. Extracellular vesicles in the antiphospholipid syndrome. Semin. Thromb. Hemost.https://doi.org/10.1055/s-0037-1599081 (2017).
Lutters, B. C. et al. Dimers of β2-glycoprotein I increase platelet deposition to collagen via interaction with phospholipids and the apolipoprotein E receptor 2’. J. Biol. Chem. 278, 33831–33838 (2003).
de Groot, P. G. & Urbanus, R. T. Cellular signaling by antiphospholipid antibodies. J. Thromb. Haemost. 12, 773–775 (2014).
Pierangeli, S. S., Vega-Ostertag, M., Liu, X. & Girardi, G. Complement activation: a novel pathogenic mechanism in the antiphospholipid syndrome. Ann. NY Acad. Sci. 1051, 413–420 (2005).
Wahl, D., Membre, A., Perret-Guillaume, C., Regnault, V. & Lecompte, T. Mechanisms of antiphospholipid-induced thrombosis: effects on the protein C system. Curr. Rheumatol Rep. 11, 77–81 (2009).
Dahlback, B. Progress in the understanding of the protein C anticoagulant pathway. Int. J. Hematol. 79, 109–116 (2004).
Feinstein, D. I. & Rapaport, S. I. Acquired inhibitors of blood coagulation. Prog. Hemost. Thromb. 1, 75–95 (1972).
Cervera, R. et al. Morbidity and mortality in the antiphospholipid syndrome during a 10-year period: a multicentre prospective study of 1000 patients. Ann. Rheum. Dis. 74, 1011–1018 (2015).
Derksen, R. H. W. M. & de Groot, P. G. The obstetric antiphospholipid syndrome. J. Reproductive Immunol. 77, 41–50 (2008).
Chamley, L. W., Duncalf, A. M., Mitchell, M. D. & Johnson, P. M. Action of anticardiolipin and antibodies to beta2-glycoprotein-I on trophoblast proliferation as a mechanism for fetal death. Lancet 352, 1037–1038 (1998).
Di Simone, N. et al. Antiphospholipid antibodies affect trophoblast gonadotropin secretion and invasiveness by binding directly and through adhered beta2-glycoprotein I. Arthritis Rheum. 43, 140–150 (2000).
Burton, G. J., Woods, A. W., Jauniaux, E. & Kingdom, J. C. Rheological and physiological consequences of conversion of the maternal spiral arteries for uteroplacental blood flow during human pregnancy. Placenta 30, 473–482 (2009).
Chamley, L. W., Allen, J. L. & Johnson, P. M. Synthesis of β2 glycoprotein 1 by the human placenta. Placenta 18, 403–410 (1997).
Mulla, M. J. et al. Antiphospholipid antibodies induce a pro-inflammatory response in first trimester trophoblast via the TLR4/MyD88 pathway. Am. J. Reprod. Immunol. 62, 96–111 (2009).
Mulla, M. J. et al. Antiphospholipid antibodies limit trophoblast migration by reducing IL-6 production and STAT3 activity. Am. J. Reprod. Immunol. 63, 339–348 (2010).
Carroll, T. Y. et al. Modulation of trophoblast angiogenic factor secretion by antiphospholipid antibodies is not reversed by heparin. Am. J. Reprod. Immunol. 66, 286–296 (2011).
Alvarez, A. M., Mulla, M. J., Chamley, L. W., Cadavid, A. P. & Abrahams, V. M. Aspirin-triggered lipoxin prevents antiphospholipid antibody effects on human trophoblast migration and endothelial cell interactions. Arthritis Rheumatol. 67, 488–497 (2015).
Ulrich, V. et al. ApoE receptor 2 mediation of trophoblast dysfunction and pregnancy complications induced by antiphospholipid antibodies in mice. Arthritis Rheumatol. 68, 730–739 (2016).
Holers, V. M. et al. Complement C3 activation is required for antiphospholipid antibody-induced fetal loss. J. Exp. Med. 195, 211–220 (2002).
Girardi, G. et al. Complement C5a receptors and neutrophils mediate fetal injury in the antiphospholipid syndrome. J. Clin. Invest. 112, 1644–1654 (2003).
Berman, J., Girardi, G. & Salmon, J. E. TNF-α is a critical effector and a target for therapy in antiphospholipid antibody-induced pregnancy loss. J. Immunol. 174, 485–490 (2005).
Girardi, G., Yarilin, D., Thurman, J. M., Holers, V. M. & Salmon, J. E. Complement activation induces dysregulation of angiogenic factors and causes fetal rejection and growth restriction. J. Exp. Med. 203, 2165–2175 (2006).
Gelber, S. E. et al. Prevention of defective placentation and pregnancy loss by blocking innate immune pathways in a syngeneic model of placental insufficiency. J. Immunol. 195, 1129–1138 (2015).
Girardi, G., Redecha, P. & Salmon, J. E. Heparin prevents antiphospholipid antibody-induced fetal loss by inhibiting complement activation. Nat. Med. 10, 1222–1226 (2004). This study supports the role of the complement system in antiphospholipid antibody-related pregnancy morbidity in a murine model.
Shamonki, J. M., Salmon, J. E., Hyjek, E. & Baergen, R. N. Excessive complement activation is associated with placental injury in patients with antiphospholipid antibodies. Am. J. Obstet. Gynecol. 196, 167.e1–167.e5 (2007).
Cohen, D. et al. Classical complement activation as a footprint for murine and human antiphospholipid antibody-induced fetal loss. J. Pathol. 225, 502–511 (2011).
Viall, C. A. & Chamley, L. W. Histopathology in the placentae of women with antiphospholipid antibodies: a systematic review of the literature. Autoimmun. Rev. 14, 446–471 (2015).
Salmon, J. E. et al. Mutations in complement regulatory proteins predispose to preeclampsia: a genetic analysis of the PROMISSE cohort. PLoS Med. 8, e1001013 (2011).
Oku, K. et al. Complement activation in patients with primary antiphospholipid syndrome. Ann. Rheum. Dis. 68, 1030–1035 (2009).
Breen, K. A. et al. Complement activation in patients with isolated antiphospholipid antibodies or primary antiphospholipid syndrome. Thromb. Haemost. 107, 423–429 (2012).
Ritis, K. et al. A novel C5a receptor-tissue factor cross-talk in neutrophils links innate immunity to coagulation pathways. J. Immunol. 177, 4794–4802 (2006).
Kupferminc, M. J., Peaceman, A. M., Wigton, T. R., Rehnberg, K. A. & Socol, M. L. Tumor necrosis factor-α is elevated in plasma and amniotic fluid of patients with severe preeclampsia. Am. J. Obstetr. Gynecol. 170, 1752–1759 (1994).
Tosun, M. et al. Maternal and umbilical serum levels of interleukin-6, interleukin-8, and tumor necrosis factor-alpha in normal pregnancies and in pregnancies complicated by preeclampsia. J. Matern. Fetal Neonatal Med. 23, 880–886 (2010).
Pijnenborg, R. et al. Immunolocalization of tumour necrosis factor-α (TNF-α) in the placental bed of normotensive and hypertensive human pregnancies. Placenta 19, 231–239 (1998).
Yalavarthi, S. et al. Release of neutrophil extracellular traps by neutrophils stimulated with antiphospholipid antibodies: a newly identified mechanism of thrombosis in the antiphospholipid syndrome. Arthritis Rheumatol. 67, 2990–3003 (2015).
Marder, W. et al. Placental histology and neutrophil extracellular traps in lupus and pre-eclampsia pregnancies. Lupus Sci. Med. 3, e000134 (2016).
Giannakopoulos, B., Passam, F., Ioannou, Y. & Krilis, S. A. How we diagnose the antiphospholipid syndrome. Blood 113, 985–994 (2009).
Pengo, V. et al. Update of the guidelines for lupus anticoagulant detection. Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. J. Thromb. Haemost. 7, 1737–1740 (2009). This publication outlines the current SSC-ISTH guidelines for the detection of antiphospholipid antibodies.
Devreese, K. M. et al. Testing for antiphospholipid antibodies with solid phase assays: guidance from the SSC of the ISTH. J. Thromb. Haemost. 12, 792–795 (2014).
Devreese, K. M. Standardization of antiphospholipid antibody assays. Where do we stand? Lupus 21, 718–721 (2012).
Devreese, K. M. No more mixing tests required for integrated assay systems in the laboratory diagnosis of lupus anticoagulants? J. Thromb. Haemost. 8, 1120–1122 (2010).
Devreese, K. M. & de Laat, B. Mixing studies in lupus anticoagulant testing are required at least in some type of samples. J. Thromb. Haemost. 13, 1475–1478 (2015).
Tripodi, A. & Pengo, V. More on: laboratory investigation of lupus anticoagulants: mixing studies are sometimes required. J. Thromb. Haemost. 9, 2126–2127 (2011).
Devreese, K. M. J. Antiphospholipid antibody testing and standardization. Int. J. Lab. Hematol. 36, 352–363 (2014).
Hoxha, A., Banzato, A., Ruffatti, A. & Pengo, V. Detection of lupus anticoagulant in the era of direct oral anticoagulants. Autoimmun. Rev. 16, 173–178 (2017).
Moore, G. W. Combining Taipan snake venom time/Ecarin time screening with the mixing studies of conventional assays increases detection rates of lupus anticoagulants in orally anticoagulated patients. Thromb. J. 5, 12 (2007).
Devreese, K. M. Antiphospholipid antibody testing and standardization. Int. J. Lab. Hematol. 36, 352–363 (2014).
Galli, M. et al. Anticardiolipin antibodies (ACA) directed not to cardiolipin but to a plasma protein cofactor. Lancet 335, 1544–1547 (1990).
Van Hoecke, F., Persijn, L., Decavele, A. S. & Devreese, K. Performance of two new, automated chemiluminescence assay panels for anticardiolipin and anti-beta2-glycoprotein I antibodies in the laboratory diagnosis of the antiphospholipid syndrome. Int. J. Lab. Hematol. 34, 630–640 (2012).
de Moerloose, P., Reber, G., Musial, J. & Arnout, J. Analytical and clinical performance of a new, automated assay panel for the diagnosis of antiphospholipid syndrome. J. Thromb. Haemost. 8, 1540–1546 (2010).
Kelchtermans, H., Pelkmans, L., de Laat, B. & Devreese, K. M. IgG/IgM antiphospholipid antibodies present in the classification criteria for the antiphospholipid syndrome: a critical review of their association with thrombosis. J. Thromb. Haemost. 14, 1530–1548 (2016).
Pericleous, C. et al. Measuring IgA anti-β2-glycoprotein I and IgG/IgA anti-domain I antibodies adds value to current serological assays for the antiphospholipid syndrome. PLoS ONE 11, e0156407 (2016).
Bertolaccini, M. L. et al. 14th International Congress on Antiphospholipid Antibodies Task Force. Report on antiphospholipid syndrome laboratory diagnostics and trends. Autoimmun. Rev. 13, 917–930 (2014).
Favaloro, E. J., Wheatland, L., Jovanovich, S., Roberts-Thomson, P. & Wong, R. C. Internal quality control and external quality assurance in testing for antiphospholipid antibodies: Part I−-Anticardiolipin and anti-beta2-glycoprotein I antibodies. Semin. Thromb. Hemost 38, 390–403 (2012).
Pelkmans, L. et al. Variability in exposure of epitope G40-R43 of domain i in commercial anti-beta2-glycoprotein I IgG ELISAs. PLoS ONE 8, e71402 (2013).
Devreese, K. M. et al. A multicenter study to assess the reproducibility of antiphospholipid antibody results produced by an automated system. J. Thromb. Haemost. 15, 91–95 (2017).
Devreese, K. M. Antiphospholipid antibodies: evaluation of the thrombotic risk. Thromb. Res. 130 (Suppl. 1), S37–S40 (2012).
Devreese, K., Peerlinck, K. & Hoylaerts, M. F. Thrombotic risk assessment in the antiphospholipid syndrome requires more than the quantification of lupus anticoagulants. Blood 115, 870–878 (2010).
Devreese, K., Peerlinck, K. & Hoylaerts, M. F. Diagnostic test combinations associated with thrombosis in lupus anticoagulant positive patients. Thromb. Haemost. 105, 736–738 (2011).
Pengo, V. et al. Antibody profiles for the diagnosis of antiphospholipid syndrome. Thromb. Haemost. 93, 1147–1152 (2005).
Pengo, V. et al. Clinical course of high-risk patients diagnosed with antiphospholipid syndrome. J. Thromb. Haemost. 8, 237–242 (2010).
Pengo, V. Four good reasons to appreciate triple positivity. Pol. Arch. Med. Wewn 126, 7–8 (2016).
Mustonen, P., Lehtonen, K. V., Javela, K. & Puurunen, M. Persistent antiphospholipid antibody (aPL) in asymptomatic carriers as a risk factor for future thrombotic events: a nationwide prospective study. Lupus 23, 1468–1476 (2014).
Pengo, V. et al. Confirmation of initial antiphospholipid antibody positivity depends on the antiphospholipid antibody profile. J. Thromb. Haemost. 11, 1527–1531 (2013).
Pengo, V. et al. APS — diagnostics and challenges for the future. Autoimmun. Rev. 15, 1031–1033 (2016).
Devreese, K. & Hoylaerts, M. F. Challenges in the diagnosis of the antiphospholipid syndrome. Clin. Chem. 56, 930–940 (2010).
Rodriguez-Garcia, V., Ioannou, Y., Fernandez-Nebro, A., Isenberg, D. A. & Giles, I. P. Examining the prevalence of non-criteria anti phospholipid antibodies in patients with anti phospholipid syndrome: a systematic review. Rheumatology 54, 2042–2050 (2015).
de Laat, B., Derksen, R. H., Urbanus, R. T. & de Groot, P. G. IgG antibodies that recognize epitope Gly40-Arg43 in domain I of β2-glycoprotein I cause LAC, and their presence correlates strongly with thrombosis. Blood 105, 1540–1545 (2005).
de Laat, B. et al. The association between circulating antibodies against domain I of β2-glycoprotein I and thrombosis: an international multicenter study. J. Thromb. Haemost. 7, 1767–1773 (2009).
Mahler, M. et al. Autoantibodies to domain 1 of beta 2 glycoprotein I determined using a novel chemiluminescence immunoassay demonstrate association with thrombosis in patients with antiphospholipid syndrome. Lupus 25, 911–916 (2016).
De Craemer, A. S., Musial, J. & Devreese, K. M. Role of anti-domain 1-β2 glycoprotein I antibodies in the diagnosis and risk stratification of antiphospholipid syndrome. J. Thromb. Haemost. 14, 1779–1787 (2016).
Pengo, V. et al. Antiphospholipid syndrome: antibodies to Domain 1 of β2-glycoprotein 1 correctly classify patients at risk. J. Thromb. Haemost. 13, 782–787 (2015).
Meneghel, L. et al. Detection of IgG anti-domain I β2 glycoprotein I antibodies by chemiluminescence immunoassay in primary antiphospholipid syndrome. Clin. Chim. Acta 446, 201–205 (2015).
Mondejar, R. et al. Role of antiphospholipid score and anti-β2-glycoprotein I domain I autoantibodies in the diagnosis of antiphospholipid syndrome. Clin. Chim. Acta 431, 174–178 (2014).
Zhang, S. et al. Evaluation of the diagnostic potential of antibodies to β2-glycoprotein 1 domain 1 in Chinese patients with antiphospholipid syndrome. Sci. Rep. 6, 23839 (2016).
Iwaniec, T., Kaczor, M. P., Celinska-Lowenhoff, M., Polanski, S. & Musial, J. Clinical significance of anti-domain 1 β2-glycoprotein I antibodies in antiphospholipid syndrome. Thromb. Res. 153, 90–94 (2017).
Sciascia, S. et al. Anti-prothrombin (aPT) and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies and the risk of thrombosis in the antiphospholipid syndrome. A systematic review. Thromb. Haemost. 111, 354–364 (2014).
Cervera, R. et al. Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis Rheum. 46, 1019–1027 (2002).
Ruiz-Irastorza, G., Hunt, B. J. & Khamashta, M. A. A systematic review of secondary thromboprophylaxis in patients with antiphospholipid antibodies. Arthritis Rheum. 57, 1487–1495 (2007).
Khamashta, M., Taraborelli, M., Sciascia, S. & Tincani, A. Antiphospholipid syndrome. Best Pract. Res. Clin. Rheumatol. 30, 133–148 (2016).
Mekinian, A. L. et al. European registry of babies born to mothers with antiphospholipid syndrome. Ann. Rheum. Dis. 72, 217–222 (2013).
Fredi, M. et al. Multicenter evaluation of obstetric and maternal outcome in prospectively followed pregnant patients with confirmed positivity for antiphospholipid antibodies (aPL) [abstract]. Arthritis Rheumatol. 67 (suppl 10), 2530 (2015).
Yelnik, C. M. et al. Lupus anticoagulant is the main predictor of adverse pregnancy outcomes in aPL-positive patients: validation of PROMISSE study results. Lupus Sci. Med. 3, e000131 (2016).
Carbillon, L., Uzan, M. & Uzan, S. Pregnancy, vascular tone, and maternal hemodynamics: a crucial adaptation. Obstet. Gynecol. Surv. 55, 574–581 (2000).
Le Thi Huong, D. W. et al. The second trimester Doppler ultrasound examination is the best predictor of late pregnancy outcome in systemic lupus erythematosus and/or the antiphospholipid syndrome. Rheumatology 45, 332–338 (2006).
Stone, S. H., B. J., Khamashta, M. A., Bewley, S. J. & Nelson-Piercy, C. Primary antiphospholipid syndrome in pregnancy: An analysis of outcome in a cohort of 33 women treated with a rigorous protocol. Editorial comment. Obstet. Gynecol. Surv. 60, 501–503 (2005).
Andreoli, L. et al. EULAR recommendations for women's health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome. Ann. Rheum. Dis. 76, 476–485 (2017).
Rodrigues, C. E., Carvalho, J. F. & Shoenfeld, Y. Neurological manifestations of antiphospholipid syndrome. Eur. J. Clin. Invest. 40, 350–359 (2010).
Shoenfeld, Y. et al. Features associated with epilepsy in the antiphospholipid syndrome. J. Rheumatol 31, 1344–1348 (2004).
Soltesz, P., Szekanecz, Z., Kiss, E. & Shoenfeld, Y. Cardiac manifestations in antiphospholipid syndrome. Autoimmun. Rev. 6, 379–386 (2007).
Ziporen, L. et al. Libman-Sacks endocarditis in the antiphospholipid syndrome: immunopathologic findings in deformed heart valves. Lupus 5, 196–205 (1996).
Cervera, R. et al. Task Force on Catastrophic Antiphospholipid Syndrome (APS) and Non-criteria APS Manifestations (I): catastrophic APS, APS nephropathy and heart valve lesions. Lupus 20, 165–173 (2011).
Nesher, G., Ilany, J., Rosenmann, D. & Abraham, A. S. Valvular dysfunction in antiphospholipid syndrome: prevalence, clinical features, and treatment. Semin. Arthritis Rheum. 27, 27–35 (1997).
Shoenfeld, Y. et al. Accelerated atherosclerosis in autoimmune rheumatic diseases. Circulation 112, 3337–3347 (2005).
Krause, I. et al. The association of thrombocytopenia with systemic manifestations in the antiphospholipid syndrome. Immunobiology 210, 749–754 (2005).
Rottem, M. et al. Autoimmune hemolytic anaemia in the antiphospholipid syndrome. Lupus 15, 473–477 (2006).
Stojanovich, L. et al. Pulmonary events in antiphospholipid syndrome: influence of antiphospholipid antibody type and levels. Scand. J. Rheumatol 41, 223–226 (2012).
Frances, C. et al. Dermatologic manifestations of the antiphospholipid syndrome: two hundred consecutive cases. Arthritis Rheum. 52, 1785–1793 (2005).
Frances, C. et al. Sneddon syndrome with or without antiphospholipid antibodies. A comparative study in 46 patients. Med. (Baltimore) 78, 209–219 (1999).
Toubi, E. & Shoenfeld, Y. Livedo reticularis as a criterion for antiphospholipid syndrome. Clin. Rev. Allergy Immunol. 32, 138–144 (2007).
Tektonidou, M. G. Identification and treatment of APS renal involvement. Lupus 23, 1276–1278 (2014).
Chaturvedi, S., Brandao, L., Geary, D. & Licht, C. Primary antiphospholipid syndrome presenting as renal vein thrombosis and membranous nephropathy. Pediatr. Nephrol. 26, 979–985 (2011).
Asherson, R. A. et al. Catastrophic antiphospholipid syndrome: international consensus statement on classification criteria and treatment guidelines. Lupus 12, 530–534 (2003).
Tektonidou, M. G., Ioannidis, J. P., Boki, K. A., Vlachoyiannopoulos, P. G. & Moutsopoulos, H. M. Prognostic factors and clustering of serious clinical outcomes in antiphospholipid syndrome. QJM 93, 523–530 (2000).
Danowski, A., de Azevedo, M. N., de Souza Papi, J. A. & Petri, M. Determinants of risk for venous and arterial thrombosis in primary antiphospholipid syndrome and in antiphospholipid syndrome with systemic lupus erythematosus. J. Rheumatol. 36, 1195–1199 (2009).
Erkan, D. et al. Aspirin for primary thrombosis prevention in the antiphospholipid syndrome: a randomized, double-blind, placebo-controlled trial in asymptomatic antiphospholipid antibody-positive individuals. Arthritis Rheum. 56, 2382–2391 (2007).
Arnaud, L. et al. Efficacy of aspirin for the primary prevention of thrombosis in patients with antiphospholipid antibodies: an international and collaborative meta-analysis. Autoimmun. Rev. 13, 281–291 (2014).
Antithrombotic Trialists, C. et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet 373, 1849–1860 (2009).
Wallace, D. J., Gudsoorkar, V. S., Weisman, M. H. & Venuturupalli, S. R. New insights into mechanisms of therapeutic effects of antimalarial agents in SLE. Nat. Rev. Rheumatol. 8, 522–533 (2012).
Bertolaccini, M. L. et al. Complement inhibition by hydroxychloroquine prevents placental and fetal brain abnormalities in antiphospholipid syndrome. J. Autoimmun. 75, 30–38 (2016).
US National Library of Medicine. ClinicalTrials.govhttp://www.clinicaltrials.gov/ct2/show/NCT01784523 (2017).
Erkan, D. et al. High thrombosis rate after fetal loss in antiphospholipid syndrome: effective prophylaxis with aspirin. Arthritis Rheum. 44, 1466–1467 (2001).
Bertsias, G. et al. EULAR recommendations for the management of systemic lupus erythematosus. Report of a Task Force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics. Ann. Rheum. Dis. 67, 195–205 (2008).
Cohen, H., Efthymiou, M., Gates, C. & Isenberg, D. Direct oral anticoagulants for thromboprophylaxis in patients with antiphospholipid syndrome. Semin. Thromb. Hemost.https://doi.org/10.1055/s-0036-1597902 (2017).
Lim, W., Crowther, M. A. & Eikelboom, J. W. Management of antiphospholipid antibody syndrome: a systematic review. JAMA 295, 1050–1057 (2006).
Finazzi, G. et al. A randomized clinical trial of high-intensity warfarin versus conventional antithrombotic therapy for the prevention of recurrent thrombosis in patients with the antiphospholipid syndrome (WAPS). J. Thromb. Haemost. 3, 848–853 (2005).
Crowther, M. A. et al. A comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome. N. Engl. J. Med. 349, 1133–1138 (2003).
Cohen, H. et al. Rivaroxaban versus warfarin to treat patients with thrombotic antiphospholipid syndrome, with or without systemic lupus erythematosus (RAPS): a randomised, controlled, open-label, phase 2/3, non-inferiority trial. Lancet Haematol. 3, e426–436 (2016). This is the first RCT of DOACs versus warfarin in APS.
Arachchillage, D. R. et al. Rivaroxaban limits complement activation compared with warfarin in antiphospholipid syndrome patients with venous thromboembolism. J. Thromb. Haemost. 14, 2177–2186 (2016).
US National Library of Medicine. ClinicalTrials.govhttp://www.clinicaltrials.gov/ct2/show/NCT02926170 (2016).
US National Library of Medicine. ClinicalTrials.govhttp://www.clinicaltrials.gov/ct2/show/NCT02157272 (2017).
US National Library of Medicine. ClinicalTrials.govhttp://www.clinicaltrials.gov/ct2/show/NCT02295475 (2017).
Crowley, M. P., Cuadrado, M. J. & Hunt, B. J. Catastrophic antiphospholipid syndrome on switching from warfarin to rivaroxaban. Thromb. Res. 153, 37–39 (2017).
Schaefer, J. K. et al. Failure of dabigatran and rivaroxaban to prevent thromboembolism in antiphospholipid syndrome: a case series of three patients. Thromb. Haemost. 112, 947–950 (2014).
Win, K. & Rodgers, G. M. New oral anticoagulants may not be effective to prevent venous thromboembolism in patients with antiphospholipid syndrome. Am. J. Hematol. 89, 1017 (2014).
Levine, S. R. et al. Antiphospholipid antibodies and subsequent thrombo-occlusive events in patients with ischemic stroke. JAMA 291, 576–584 (2004).
Molad, Y. et al. Protective effect of hydroxychloroquine in systemic lupus erythematosus. Prospective long-term study of an Israeli cohort. Lupus 11, 356–361 (2002).
Ruiz-Irastorza, G. et al. Effect of antimalarials on thrombosis and survival in patients with systemic lupus erythematosus. Lupus 15, 577–583 (2006). This study emphasizes the antithrombotic effect of antimalarials in individuals with SLE.
Schmidt-Tanguy, A. et al. Antithrombotic effects of hydroxychloroquine in primary antiphospholipid syndrome patients. J. Thromb. Haemost. 11, 1927–1929 (2013).
Schreiber, K. et al. The effect of hydroxychloroquine on haemostasis, complement, inflammation and angiogenesis in patients with antiphospholipid antibodies. Rheumatologyhttps://doi.org/10.1093/rheumatology/kex378 (2017). This paper suggests that hydroxychloroquine reduces soluble tissue factor in patients with APS.
Cervera, R. & Group, C. R. P. Catastrophic antiphospholipid syndrome (CAPS): update from the ‘CAPS Registry’. Lupus 19, 412–418 (2010).
Cervera, R. et al. Task Force on Catastrophic Antiphospholipid Syndrome (APS) and Non-criteria APS Manifestations (II): thrombocytopenia and skin manifestations. Lupus 20, 174–181 (2011).
Bazzan, M. et al. Patients with antiphosholipid syndrome and thrombotic recurrences: A real world observation (the Piedmont cohort study). Lupus 25, 479–485 (2016).
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 49, 281–288 (2010).
Bramham, K. et al. Pregnancy outcome in different clinical phenotypes of antiphospholipid syndrome. Lupus 19, 58–64 (2010).
Fischer-Betz, R. S., C., Brinks, R. & Schneider, M. Pregnancy outcome in patients with antiphospholipid syndrome after cerebral ischaemic events: an observational study. Lupus 21, 1183–1189 (2012).
Sliwa, K. et al. Pulmonary hypertension and pregnancy outcomes: data from the Registry Of Pregnancy and Cardiac Disease (ROPAC) of the European Society of Cardiology. Eur. J. Heart Fail. 18, 1119–1128 (2016).
Bouvier, S. et al. Comparative incidence of pregnancy outcomes in treated obstetric antiphospholipid syndrome: the NOH-APS observational study. Blood 123, 404–413 (2014).
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 314, 253–257 (1997).
Kutteh, W. H. Antiphospholipid antibody-associated recurrent pregnancy loss: treatment with heparin and low-dose aspirin is superior to low-dose aspirin alone. Am. J. Obstet. Gynecol. 174, 1584–1589 (1996).
Farquharson, R. G., Quenby, S. & Greaves, M. Antiphospholipid syndrome in pregnancy: a randomized, controlled trial of treatment. Obstet. Gynecol. 100, 408–413 (2002).
Laskin, C. A. S. et al. Low molecular weight heparin and aspirin for recurrent pregnancy loss: results from the randomized, controlled HepASA Trial. J. Rheumatol. 36, 279–287 (2009).
Noble, L. S. K., W. H., Lashey, N., Franklin, R. D. & Herrada, J. Antiphospholipid antibodies associated with recurrent pregnancy loss: prospective, multicenter, controlled pilot study comparing treatment with low-molecular-weight heparin versus unfractionated heparin. Fertil. Steril. 83, 684–690 (2005).
Fouda, U. M. et al. Enoxaparin versus unfractionated heparin in the management of recurrent abortion secondary to antiphospholipid syndrome. Int. J. Gynaecol. Obstet. 112, 211–215 (2011).
Empson, M., Lassere, M., Craig, J. & Scott, J. Prevention of recurrent miscarriage for women with antiphospholipid antibody or lupus anticoagulant. Cochrane Database Syst Rev. 2, CD002859 (2005).
National Collaborating Centre for Women's and Children's Health (UK). Hypertension in Pregnancy: The Management of Hypertensive Disorders During Pregnancy (RCOG Press, 2010).
Henderson, J. T. et al. Low-dose aspirin for prevention of morbidity and mortality from preeclampsia: a systematic evidence review for the U.S. Preventive Services Task Force. Ann. Intern. Med. 160, 695–703 (2014).
Lausman, A., Kingdom, J. & Maternal Fetal Medicine, C. Intrauterine growth restriction: screening, diagnosis, and management. J. Obstet. Gynaecol. Can. 35, 741–748 (2013).
Bramham, K., Thomas, M., Nelson-Piercy, C., Khamashta, M. & Hunt, B. J. First-trimester low-dose prednisolone in refractory antiphospholipid antibody-related pregnancy loss. Blood 117, 6948–6951 (2011).
Triolo, G. et al. Randomized study of subcutaneous low molecular weight heparin plus aspirin versus intravenous immunoglobulin in the treatment of recurrent fetal loss associated with antiphospholipid antibodies. Arthritis Rheum. 48, 728–731 (2003).
Branch, D. W. et al. A multicenter, placebo-controlled pilot study of intravenous immune globulin treatment of antiphospholipid syndrome during pregnancy. Am. J. Obstet. Gynecol. 182, 122–127 (2000).
Tincani, A., Scarsi, M., Franceschini, F. & Cattaneo, R. Intravenous immunoglobulin in pregnancy: a chance for patients with an autoimmune disease. Isr. Med. Assoc. J. 9, 553–554 (2007).
Lefkou, E. et al. Pravastatin improves pregnancy outcomes in obstetric antiphospholipid syndrome refractory to antithrombotic therapy. J. Clin. Invest. 126, 2933–2940 (2016). This case-control study highlights the potential role of pravastatin in refractory obstetrical APS.
Sciascia, S. et al. The impact of hydroxychloroquine treatment on pregnancy outcome in women with antiphospholipid antibodies. Am. J. Obstet. Gynecol. 214, 273.e1–273.e8 (2016). This paper highlights the possible role of hydroxychloroquine in improving antiphospholipid antibody-related pregnancy outcomes.
Mekinian, A. et al. The efficacy of hydroxychloroquine for obstetrical outcome in anti-phospholipid syndrome: data from a European multicenter retrospective study. Autoimmun. Rev. 14, 498–502 (2015).
Schreiber, K. 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. 43, 562–571 (2017).
van Hoorn, M. E. et al. 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. 197, 168–173 (2016).
Rodger, M. A. et al. Antepartum dalteparin versus no antepartum dalteparin for the prevention of pregnancy complications in pregnant women with thrombophilia (TIPPS): a multinational open-label randomised trial. Lancet 384, 1673–1683 (2014).
van Korlaar, I. M. et al. The impact of venous thrombosis on quality of life. Thromb. Res. 114, 11–18 (2004).
Balitsky, A. K. et al. Thrombovascular events affect quality of life in patients with systemic lupus erythematosus. J. Rheumatol 38, 1017–1019 (2011).
Georgopoulou, S., Efraimidou, S., MacLennan, S. J., Ibrahim, F. & Cox, T. Antiphospholipid (Hughes) syndrome: description of population and health-related quality of life (HRQoL) using the SF-36. Lupus 24, 174–179 (2015).
Georgopoulou, S., Efraimidou, S., MacLennan, S. J., Ibrahim, F. & Cox, T. The relationship between social support and health-related quality of life in patients with antiphospholipid (hughes) syndrome. Mod. Rheumatol.https://doi.org/10.1080/14397595.2017.1317319 (2017).
Alarcon-Segovia, D., Perez-Vazquez, M. E., Villa, A. R., Drenkard, C. & Cabiedes, J. Preliminary classification criteria for the antiphospholipid syndrome within systemic lupus erythematosus. Semin. Arthritis Rheum. 21, 275–286 (1992).
Erkan, D. & Lockshin, M. D. Non-criteria manifestations of antiphospholipid syndrome. Lupus 19, 424–427 (2010).
Abreu, M. M. et al. The relevance of “non-criteria” clinical manifestations of antiphospholipid syndrome: 14th International Congress on Antiphospholipid Antibodies Technical Task Force Report on Antiphospholipid Syndrome Clinical Features. Autoimmun. Rev. 14, 401–414 (2015).
Sciascia, S., Bertolaccini, M. L., Roccatello, D. & Khamashta, M. A. Independent validation of the antiphospholipid score for the diagnosis of antiphospholipid syndrome. Ann. Rheum. Dis. 72, 142–143 (2013). This paper outlines the development of the GAPSS.
Sciascia, S. S. et al. The global anti-phospholipid syndrome score in primary APS. Rheumatology 54, 134–138 (2015).
Sciascia, S. et al. Thrombotic risk assessment in systemic lupus erythematosus: validation of the global antiphospholipid syndrome score in a prospective cohort. Arthritis Care Res. 66, 1915–1920 (2014).
Zuily, S. et al. Validity of the global anti-phospholipid syndrome score to predict thrombosis: a prospective multicentre cohort study. Rheumatology 54, 2071–2075 (2015).
Oku, K. et al. An independent validation of the Global Anti-Phospholipid Syndrome Score in a Japanese cohort of patients with autoimmune diseases. Lupus 24, 774–775 (2015).
Glynn, R. J. et al. A randomized trial of rosuvastatin in the prevention of venous thromboembolism. N. Engl. J. Med. 360, 1851–1861 (2009).
Erkan, D. et al. A prospective open-label pilot study of fluvastatin on proinflammatory and prothrombotic biomarkers in antiphospholipid antibody positive patients. Ann. Rheum. Dis. 73, 1176–1180 (2014).
Unlu, O. & Erkan, D. Catastrophic antiphospholipid syndrome: candidate therapies for a potentially lethal disease. Annu. Rev. Med. 68, 287–296 (2017).
Leone, A. et al. Autologous hematopoietic stem cell transplantation in Systemic Lupus Erythematosus and antiphospholipid syndrome: a systematic review. Autoimmun. Rev. 16, 469–477 (2017).
Abrahams, V. M., Chamley, L. W. & Salmon, J. E. Emerging treatment models in rheumatology: antiphospholipid syndrome and pregnancy: pathogenesis to translation. Arthritis Rheumatol. 69, 1710–1721 (2017).
Petri, M. Epidemiology of the antiphospholipid antibody syndrome. J. Autoimmun. 15, 145–151 (2000).
Deeb, A., Hamdoun, S. & Dababo, K. Prevalence of antiphospholipid antibodies in Syrian patients with thrombosis. Iran. J. Immunol. 6, 154–159 (2009).
Galli, M., Luciani, D., Bertolini, G. & Barbui, T. Anti-β2-glycoprotein I, antiprothrombin antibodies, and the risk of thrombosis in the antiphospholipid syndrome. Blood 102, 2717–2723 (2003).
Ginsburg, K. S. et al. Anticardiolipin antibodies and the risk for ischemic stroke and venous thrombosis. Ann. Intern. Med. 117, 997–1002 (1992).
de Groot, P. G. et al. Lupus anticoagulants and the risk of a first episode of deep venous thrombosis. J. Thromb. Haemost. 3, 1993–1997 (2005).
Meroni, P. L. et al. Anti-beta 2 glycoprotein I antibodies and the risk of myocardial infarction in young premenopausal women. J. Thromb. Haemost. 5, 2421–2428 (2007).
[No authors listed.] Anticardiolipin antibodies and the risk of recurrent thrombo-occlusive events and death. The Antiphospholipid Antibodies and Stroke Study Group (APASS). Neurology 48, 91–94 (1997).
Sciascia, S. et al. The estimated frequency of antiphospholipid antibodies in young adults with cerebrovascular events: a systematic review. Ann. Rheum. Dis. 74, 2028–2033 (2015).
Opatrny, L., David, M., Kahn, S. R., Shrier, I. & Rey, E. Association between antiphospholipid antibodies and recurrent fetal loss in women without autoimmune disease: a metaanalysis. J. Rheumatol 33, 2214–2221 (2006).
Kumar, K. S. J., A., Prakash, M. S., Rani, H. S. & Reddy, P. P. Beta2-glycoprotein I dependent anticardiolipin antibodies and lupus anticoagulant in patients with recurrent pregnancy loss. J. Postgrad. Med. 48, 5–10 (2002).
Mtiraoui, N. et al. Prevalence of antiphospholipid antibodies, factor V G1691A (Leiden) and prothrombin G20210A mutations in early and late recurrent pregnancy loss. Eur. J. Obstet. Gynecol. Reprod. Biol. 119, 164–170 (2005).
Rolnik, D. L. et al. Aspirin versus placebo in pregnancies at high risk for preterm preeclampsia. N. Engl. J. Med. 377, 613–622 (2017).
Rey, E. et al. Dalteparin for the prevention of recurrence of placental-mediated complications of pregnancy in women without thrombophilia: a pilot randomized controlled trial. J. Thromb. Haemost. 7, 58–64 (2009).
Flint, J. et al. BSR and BHPR guideline on prescribing drugs in pregnancy and breastfeeding — part I: standard and biologic disease modifying anti-rheumatic drugs and corticosteroids. Rheumatology 55, 1693–1697 (2016).
Flint, J. et al. BSR and BHPR guideline on prescribing drugs in pregnancy and breastfeeding — part II: analgesics and other drugs used in rheumatology practice. Rheumatology 55, 1698–1702 (2016).
Royal College of Obstetricians and Gynaecologists. Reducing the Risk of Venous Thromboembolism during Pregnancy and the Puerperium. Green-top Guideline No. 37a (Royal College of Obstetricians and Gynaecologists, 2015).
The authors thank the Guy's and St Thomas’ Charity for their support of K.S.
J.E.S. has received an investigator-initiated grant from UCB. The other authors declare no competing interests.
About this article
Cite this article
Schreiber, K., Sciascia, S., de Groot, P. et al. Antiphospholipid syndrome. Nat Rev Dis Primers 4, 17103 (2018). https://doi.org/10.1038/nrdp.2017.103
Modern Rheumatology (2020)
American Journal of Reproductive Immunology (2020)
Direct oral anticoagulants versus vitamin K antagonists in antiphospholipid syndrome: A meta-analysis.
European Journal of Internal Medicine (2020)
International Journal of Laboratory Hematology (2020)
Journal of Internal Medicine (2020)