Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Current Rheumatology Reports
Published in: Current Rheumatology Reports 12/2021

01-12-2021 | Direct Oral Anticoagulant | Systemic Lupus Erythematosus (G Tsokos, Section Editor)

An Update on Antiphospholipid Syndrome

Authors: Eleni Xourgia, Maria G. Tektonidou

Published in: Current Rheumatology Reports | Issue 12/2021

Login to get access

Abstract

Purpose of Review

To review the recent available evidence on epidemiology, pathogenesis, clinical phenotypes, and management of antiphospholipid syndrome (APS) and summarize potential future research perspectives.

Recent Findings

Accumulating evidence has further expanded our understanding of the disease, including new data about the incidence and prevalence of APS, novel pathways supporting the role of thrombo-inflammation in APS including platelet, monocyte and endothelial cell activation, pro-inflammatory cytokine and chemokine production, complement activation, neutrophil extracellular trap release, and type I interferon gene expression that could yield to new potential treatment targets, better identification of criteria and non-criteria clinical phenotypes, antiphospholipid antibody profiles and their associations with clinical outcomes, prognostic tools, and treatment strategies based on recent evidence-based recommendations for patients with thrombotic and obstetric APS, with or without systemic lupus erythematosus.

Summary

Ongoing research efforts and international collaborations enhance our knowledge of this rare and often devastating syndrome and help improve patient care and health outcomes.
Literature
1.
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(6):1011–8.PubMed
2.
Erkan D, Sciascia S, Bertolaccini ML, Cohen H; APS ACTION Executive Committee. Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION): 10-Year Update. Curr Rheumatol Rep. 2021;23(6):45. (This update on the APS ACTION international research network reviewed the scientific contributions of most recent years and set the stage for continuing advancement in APS research)
3.
Duarte-García A, Pham MM, Crowson CS, Amin S, Moder KG, Pruthi RK, et al. The epidemiology of antiphospholipid syndrome: a population-based study. Arthritis Rheumatol. 2019;71(9):1545–52.PubMedPubMedCentral
4.
Radin M, Sciascia S, Bazzan M, Bertero T, Carignola R, Montabone E, 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 Rheumatol 2020;72(10):1774–6.
5.
Giannakopoulos B, Krilis SA. The pathogenesis of the antiphospholipid syndrome. N Engl J Med. 2013;368(11):1033–44.PubMed
6.
Chighizola CB, Raschi E, Borghi MO, Meroni PL. Update on the pathogenesis and treatment of the antiphospholipid syndrome. Curr Opin Rheumatol. 2015;27(5):476–82.PubMed
7.
Corban MT, Ali Duarte-Garcia A, McBane RB, Matteson EL, Lerman LO, Lerman A. Antiphospholipid syndrome: role of vascular endothelial cells and implications for risk stratification and targeted therapeutics. J Am Coll Cardiol. 2017;69(18):2317–30.PubMed
8.
de Groot PG, de Laat B. Mechanisms of thrombosis in systemic lupus erythematosus and antiphospholipid syndrome. Best Pract Res Clin Rheumatol. 2017;31(3):334–41.PubMed
9.
Zhang W, Gao F, Lu D, Sun N, Yin X, Jin M, 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. Front Med. 2016;10(1):76–84.PubMed
10.
Baroni G, Banzato A, Bison E, Denas G, Zoppellaro G, Pengo V. The role of platelets in antiphospholipid syndrome. Platelets. 2017;28(8):762–6.PubMed
11.
Huang S, Ninivaggi M, Chayoua W, de Laat B. VWF, platelets and the antiphospholipid syndrome. Int J Mol Sci. 2021;22(8):4200.PubMedPubMedCentral
12.
Krilis M, Qi M, Ioannou Y, Zhang JY, Ahmadi Z, Wong JWH, et al. Clinical relevance of nitrated beta 2-glycoprotein I in antiphospholipid syndrome: Implications for thrombosis risk. J Autoimmun. 2021;122:102675.PubMed
13.
Liu T, Han J, Zhang R, Tang Z, Yi G, Gong W, et al. Characteristics of purified Anti-β2GPI IgG N-glycosylation associate with thrombotic, obstetric, and catastrophic antiphospholipid syndrome. Rheumatol Oxf Engl. 2021;keab416.
14.
Patsouras MD, Sikara MP, Grika EP, Moutsopoulos HM, Tzioufas AG, Vlachoyiannopoulos PG. Elevated expression of platelet-derived chemokines in patients with antiphospholipid syndrome. J Autoimmun. 2015;1(65):30–7.
15.
Tektonidou MG, Kravvariti E, Vlachogiannis NI, Georgiopoulos G, Mantzou A, Sfikakis PP, et al. Clinical value of amyloid-beta1-40 as a marker of thrombo-inflammation in antiphospholipid syndrome. Rheumatol Oxf Engl. 2021;60(4):1669–75.
16.
Samudra AN, Dwyer KM, Selan C, Freddi S, Murray-Segal L, Nikpour M, et al. CD39 and CD73 activity are protective in a mouse model of antiphospholipid antibody-induced miscarriages. J Autoimmun. 2018;88:131–8.PubMed
17.
Kim MY, Guerra MM, Kaplowitz E, Laskin CA, Petri M, Branch W, et al. Complement activation predicts adverse pregnancy outcome in patients with systemic lupus erythematosus and/or antiphospholipid antibodies. Ann Rheum Dis. 2018;77(4):549–55.PubMed
18.
Chaturvedi S, Braunstein EM, Yuan X, Yu J, Alexander A, Chen H, et al. Complement activity and complement regulatory gene mutations are associated with thrombosis in APS and CAPS. Blood. 2020;135(4):239–51.PubMedPubMedCentral
19.
Geethakumari PR, Mille P, Gulati R, Nagalla S. Complement inhibition with eculizumab for thrombotic microangiopathy rescues a living-donor kidney transplant in a patient with antiphospholipid antibody syndrome. Transfus Apher Sci. 2017;56(3):400–3.PubMed
20.
Tedesco F, Borghi MO, Gerosa M, Chighizola CB, Macor P, Lonati PA, et al. Pathogenic role of complement in antiphospholipid syndrome and therapeutic implications. Front Immunol. 2018;19(9):1388.
21.
Tambralli A, Gockman K, Knight JS. NETs in APS: current knowledge and future perspectives. Curr Rheumatol Rep. 2020;22(10):67.PubMed
22.
Sule G, Kelley WJ, Gockman K, Yalavarthi S, Vreede AP, Banka AL, et al. Increased adhesive potential of antiphospholipid syndrome neutrophils mediated by β2 integrin Mac-1. Arthritis Rheumatol Hoboken NJ. 2020;72(1):114–24.
23.
Knight JS, Meng H, Coit P, Yalavarthi S, Sule G, Gandhi AA, et al. Activated signature of antiphospholipid syndrome neutrophils reveals potential therapeutic target. JCI Insight. 2017;2(18):93897.PubMed
24.
Ali RA, Gandhi AA, Meng H, Yalavarthi S, Vreede AP, Estes SK, et al. Adenosine receptor agonism protects against NETosis and thrombosis in antiphospholipid syndrome. Nat Commun. 2019;10(1):1916.PubMedPubMedCentral
25.
Zha C, Zhang W, Gao F, Xu J, Jia R, Cai J, et al. Anti-β2GPI/β2GPI induces neutrophil extracellular traps formation to promote thrombogenesis via the TLR4/MyD88/MAPKs axis activation. Neuropharmacology. 2018;138:140–50.PubMed
26.
Xourgia E, Tektonidou MG. Type I interferon gene expression in antiphospholipid syndrome: Pathogenetic, clinical and therapeutic implications. J Autoimmun. 2019;104:102311.PubMed
27.
Cecchi I, Radin M, Rodríguez-Carrio J, Tambralli A, Knight JS, Sciascia S. Utilizing type I interferon expression in the identification of antiphospholipid syndrome subsets. Expert Rev Clin Immunol. 2021;17(4):395–406.PubMed
28.
Grenn RC, Yalavarthi S, Gandhi AA, Kazzaz NM, Núñez-Álvarez C, Hernández-Ramírez D, et al. Endothelial progenitor dysfunction associates with a type I interferon signature in primary antiphospholipid syndrome. Ann Rheum Dis. 2017;76(2):450–7.PubMed
29.
van den Hoogen LL, Fritsch-Stork RDE, Versnel MA, Derksen RHW, van Roon JAG, Radstake TRD. Monocyte type I interferon signature in antiphospholipid syndrome is related to proinflammatory monocyte subsets, hydroxychloroquine and statin use. Ann Rheum Dis. 2016;75(12):e81.PubMed
30.
van den Hoogen LL, Rossato M, Lopes AP, Pandit A, Bekker CPJ, Fritsch-Stork RDE, et al. microRNA downregulation in plasmacytoid dendritic cells in interferon-positive systemic lupus erythematosus and antiphospholipid syndrome. Rheumatol Oxf Engl. 2018;57(9):1669–74.
31.
Hisada R, Kato M, Sugawara E, Kanda M, Fujieda Y, Oku K, et al. Circulating plasmablasts contribute to antiphospholipid antibody production, associated with type I interferon upregulation. J Thromb Haemost JTH. 2019;17(7):1134–43.PubMed
32.
Palli E, Kravvariti E, Tektonidou MG. Type I interferon signature in primary antiphospholipid syndrome: clinical and laboratory associations. Front Immunol. 2019;10:487.PubMedPubMedCentral
33.
Ugolini-Lopes MR, Torrezan GT, Gândara APR, Olivieri EHR, Nascimento IS, Okazaki E, et al. Enhanced type I interferon gene signature in primary antiphospholipid syndrome: Association with earlier disease onset and preeclampsia. Autoimmun Rev. 2019;18(4):393–8.PubMed
34.
Flessa CM, Vlachiotis S, Nezos A, Andreakos E, CP Mavragani CP, Tektonidou MG. Independent association of low IFNλ1 gene expression and type I IFN score/IFNλ1 ratio with obstetric manifestations and triple antiphospholipid antibody positivity in primary antiphospholipid syndrome. Clin Immunol 209, 108265
35.
van den Hoogen LL, van Roon JAG, Mertens JS, Wienke J, Lopes AP, de Jager W, et al. Galectin-9 is an easy to measure biomarker for the interferon signature in systemic lupus erythematosus and antiphospholipid syndrome. Ann Rheum Dis. 2018;77(12):1810–4.PubMed
36.
Pérez-Sánchez C, Aguirre MA, Ruiz-Limón P, Barbarroja N, Jiménez-Gómez Y, de la Rosa IA, et al. Atherothrombosis-associated microRNAs in Antiphospholipid syndrome and Systemic Lupus Erythematosus patients. Sci Rep. 2016;9(6):31375.
37.
Pérez-Sánchez C, Arias-de la Rosa I, Aguirre MÁ, Luque-Tévar M, Ruiz-Limón P, Barbarroja N, et al. Circulating microRNAs as biomarkers of disease and typification of the atherothrombotic status in antiphospholipid syndrome. Haematologica. 2018;103(5):908–18.PubMedPubMedCentral
38.
Garcia D, Erkan D. Diagnosis and management of the antiphospholipid syndrome. N Engl J Med. 2018;378(21):2010–21.PubMed
39.
Sayar Z, Moll R, Isenberg D, Cohen H. Thrombotic antiphospholipid syndrome: a practical guide to diagnosis and management. Thromb Res. 2021;198:213–21.PubMed
40.
•• Sciascia S, Radin M, Cecchi I, Levy RA, Erkan D. 16th International congress on antiphospholipid antibodies task force report on clinical manifestations of antiphospholipid syndrome. Lupus. 2021;30(8):1314–26. This task force report summarized the most recent evidence in regards to APS clinical manifestationsPubMed
41.
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 JTH. 2006;4(2):295–306.PubMed
42.
Devreese KMJ, Ortel TL, Pengo V, de Laat B, Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies. Laboratory criteria for antiphospholipid syndrome: communication from the SSC of the ISTH. J Thromb Haemost JTH. 2018;16(4):809–13.
43.
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):1296–304.PubMed
44.
Devreese KMJ. Testing for antiphospholipid antibodies: advances and best practices. Int J Lab Hematol. 2020;42(Suppl 1):49–58.PubMed
45.
Bertolaccini ML, Amengual O, Andreoli L, Atsumi T, Chighizola CB, Forastiero R, et al. 14th International Congress on Antiphospholipid Antibodies Task Force. Report on antiphospholipid syndrome laboratory diagnostics and trends. Autoimmun Rev. 2014;13(9):917–30. 64.
46.
Amengual O, Forastiero R, Sugiura-Ogasawara M, Otomo K, Oku K, Favas C, et al. Evaluation of phosphatidylserine-dependent antiprothrombin antibody testing for the diagnosis of antiphospholipid syndrome: results of an international multicentre study. Lupus. 2017;26(3):266–76.PubMed
47.
•• Cervera R, Rodríguez-Pintó I, Legault K, Erkan D. 16th International Congress on Antiphospholipid Antibodies Task Force Report on Catastrophic Antiphospholipid Syndrome. Lupus. 2020;29(12):1594–600. This task force report summarized evidence and identified gaps in the literature pertaining to CAPSPubMed
48.
de Jesús GR, Benson AE, Chighizola CB, Sciascia S, Branch DW. 16th International Congress on Antiphospholipid Antibodies Task Force Report on Obstetric Antiphospholipid Syndrome. Lupus. 2020;29(12):1601–15.PubMed
49.
Serrano R, Pons-Estel GJ, Espinosa G, Quintana RM, Reverter JC, Tassies D, et al. Long-term follow-up of antiphospholipid syndrome: real-life experience from a single center. Lupus. 2020;29(9):1050–9.PubMed
50.
Taraborelli M, Reggia R, Dall’Ara F, Fredi M, Andreoli L, Gerosa M, et al. Longterm outcome of patients with primary antiphospholipid syndrome: a retrospective multicenter study. J Rheumatol. 2017;44(8):1165–72.
51.
Pineton de Chambrun M, Larcher R, Pène F, Argaud L, Mayaux J, Jamme M, et al. In-hospital mortality-associated factors in patients with thrombotic antiphospholipid syndrome requiring ICU admission. Chest. 2020;157(5):1158–66
52.
Zuily S, Clerc-Urmès I, Bauman C, Andrade D, Sciascia S, Pengo V, et al. Cluster analysis for the identification of clinical phenotypes among antiphospholipid antibody-positive patients from the APS ACTION Registry. Lupus. 2020;23:961203320940776. This study attempted to identifyspecific disease phenotypes in order to better predict patientoutcomes.
53.
Ogata Y, Fujieda Y, Sugawara M, Sato T, Ohnishi N, Kono M, et al. Morbidity and mortality in antiphospholipid syndrome based on cluster analysis: a 10-year longitudinal cohort study. Rheumatol Oxf Engl. 2021;60(3):1331–7.
54.
55.
Unlu O, Erkan D, Barbhaiya M, Andrade D, Nascimento I, Rosa R, et al. AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking Investigators. The impact of systemic lupus erythematosus on the clinical phenotype of antiphospholipid antibody-positive patients: results from the AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Clinical Database and Repository. Arthritis Care Res (Hoboken). 2019;71(1):134–141.
56.
Sevim E, Zisa D, Andrade D, Sciascia S, Pengo V, Tektonidou MG, et al. Characteristics of antiphospholipid antibody positive patients in AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking. Arthritis Care Res. 2020;
57.
Tektonidou MG, Laskari K, Panagiotakos DP, Moutsopoulos HM. Risk factors for thrombosis and primary thrombosis prevention in patients with systemic lupus erythematosus with or without antiphospholipid antibodies. Arthritis Rheum. 2009;61(1):29–36.PubMed
58.
Gkrouzman E, Sevim E, Finik J, Andrade D, Pengo V, Sciascia S, et al. Antiphospholipid antibody profile stability over time: prospective results from the APS ACTION Clinical Database and Repository. J Rheumatol. 2020;jrheum.200513.
59.
Bertolaccini ML, Amengual O, Andreoli L, Atsumi T, Chighizola CB, Forastiero R, et al. 14th International Congress on Antiphospholipid Antibodies Task Force. Report on antiphospholipid syndrome laboratory diagnostics and trends. Autoimmun Rev. 2014;13(9):917–30. 64.
60.
Sciascia S, Radin M, Cecchi I, Rubini E, Scotta A, Rolla R, et al. Reliability of lupus anticoagulant and anti-phosphatidylserine/prothrombin autoantibodies in antiphospholipid syndrome: a multicenter study. Front Immunol. 2019;5(10):376.
61.
Pengo V, Ruffatti A, Tonello M, Cuffaro S, Banzato A, Bison E, et al. Antiphospholipid syndrome: antibodies to Domain 1 of β2-glycoprotein 1 correctly classify patients at risk. J Thromb Haemost JTH. 2015;13(5):782–7.PubMed
62.
63.
Volkov I, Seguro L, Leon EP, Kovács L, Roggenbuck D, Schierack P, et al. Profiles of criteria and non-criteria anti-phospholipid autoantibodies are associated with clinical phenotypes of the antiphospholipid syndrome. Auto- Immun Highlights. 2020;11(1):8.PubMedPubMedCentral
64.
Alijotas-Reig J, Esteve-Valverde E, Ferrer-Oliveras R, Sáez-Comet L, Lefkou E, Mekinian A, et al. Comparative study of obstetric antiphospholipid syndrome (OAPS) and non-criteria obstetric APS (NC-OAPS): report of 1640 cases from the EUROAPS registry. Rheumatol Oxf Engl. 2020;59(6):1306–14.
65.
Högdén A, Antovic A, Berg E, Bremme K, Chaireti R. Obstetric outcomes in patients with primary thrombotic and obstetric antiphospholipid syndrome and its relation to the antiphospholipid antibody profile. Lupus. 2019;28(7):868–77.PubMed
66.
Nalli C, Lini D, Andreoli L, Crisafulli F, Fredi M, Lazzaroni MG, et al. Low preconception complement levels are associated with adverse pregnancy outcomes in a multicenter study of 260 pregnancies in 197 women with antiphospholipid syndrome or carriers of antiphospholipid antibodies. Biomedicines. 2021;9(6):671.PubMedPubMedCentral
67.
Jiang H, Wang C-H, Jiang N, Li J, Wu C-Y, Wang Q, et al. Clinical characteristics and prognosis of patients with isolated thrombotic vs. obstetric antiphospholipid syndrome: a prospective cohort study. Arthritis Res Ther. 2021;23(1):138.PubMedPubMedCentral
68.
Yelnik CM, Porter TF, Branch DW, Laskin CA, Merrill JT, Guerra MM, et al. Brief report: Changes in antiphospholipid antibody titers during pregnancy: effects on pregnancy outcomes. Arthritis Rheumatol Hoboken NJ. 2016;68(8):1964–9.
69.
Udry S, Latino JO, Belizna C, PerésWingeyer S, Fernández Romero DS, de Larrañaga G. A high-risk laboratory profile of antiphospholipid antibodies and thrombosis is associated with a large number of extra-criteria manifestations in obstetric antiphospholipid syndrome. Immunol Res. 2019;67(6):478–85.PubMed
70.
Tektonidou MG. Antiphospholipid syndrome nephropathy: from pathogenesis to treatment. Front Immunol. 2018;31(9):1181.
71.
Pires da Rosa G, Bettencourt P, Rodríguez-Pintó I, Cervera R, Espinosa G. “Non-criteria” antiphospholipid syndrome: a nomenclature proposal. Autoimmun Rev. 2020;19(12):102689.
72.
Kampolis C, Tektonidou M, Moyssakis I, Tzelepis GE, Moutsopoulos HM, Vlachoyiannopoulos PG. Evolution of cardiac dysfunction in patients with antiphospholipid antibodies and/or antiphospholipid syndrome: a 10-year follow-up study. Semin Arthritis Rheum. 2014;43(4):558–65.PubMed
73.
Mavrogeni SI, Markousis-Mavrogenis G, Karapanagiotou O, Toutouzas K, Argyriou P, Velitsista S, et al. Silent myocardial perfusion abnormalities detected by stress cardiovascular magnetic resonance in antiphospholipid syndrome: a case-control study. J Clin Med. 2019;8(7):1084.PubMedCentral
74.
Tektonidou MG, Varsou N, Kotoulas G, Antoniou A, Moutsopoulos HM. Cognitive deficits in patients with antiphospholipid syndrome: association with clinical, laboratory, and brain magnetic resonance imaging findings. Arch Intern Med. 2006;166(20):2278–8476.PubMed
75.
Barbhaiya M, Zuily S, Ahmadzadeh Y, Amigo M-C, Avcin T, Bertolaccini ML, et al. Development of new international antiphospholipid syndrome classification criteria phase I/II report: generation and reduction of candidate criteria. Arthritis Care Res. 2020;
76.
Otomo K, Atsumi T, Amengual O, Fujieda Y, Kato M, Oku K, Horita T, Yasuda S, Koike T. Efficacy of the antiphospholipid score for the diagnosis of antiphospholipid syndrome and its predictive value for thrombotic events. Arthritis Rheum. 2012;64(2):504.PubMed
77.
Radin M, Sciascia S, Erkan D, Pengo V, Tektonidou MG, Ugarte A, et al. The adjusted global antiphospholipid syndrome score (aGAPSS) and the risk of recurrent thrombosis: Results from the APS ACTION cohort. Semin Arthritis Rheum. 2019;49(3):464–8. This analysis suggested that aGAPSS may be a useful tool in risk stratification of APS patients.PubMedPubMedCentral
78.
Pregnolato F, Gerosa M, Raimondo MG, Comerio C, Bartoli F, Lonati PA, et al. EUREKA algorithm predicts obstetric risk and response to treatment in women with different subsets of anti-phospholipid antibodies. Rheumatology (Oxford). 2021;60(3):1114–24.
79.
Amigo M-C, Goycochea-Robles MV, Espinosa-Cuervo G, Medina G, Barragán-Garfias JA, Vargas A, et al. Development and initial validation of a damage index (DIAPS) in patients with thrombotic antiphospholipid syndrome (APS). Lupus. 2015;24(9):927–34.PubMed
80.
Erkan D, Yazici Y, Peterson MG, Sammaritano L, Lockshin MD. A cross-sectional study of clinical thrombotic risk factors and preventive treatments in antiphospholipid syndrome. Rheumatol Oxf Engl. 2002;41(8):924–9.
81.
Matyja-Bednarczyk A, Swadźba J, Iwaniec T, Sanak M, Dziedzina S, Ćmiel A, et al. Risk factors for arterial thrombosis in antiphospholipid syndrome. Thromb Res. 2014;133(2):173–6.PubMed
82.
Pengo V, Testa S, Martinelli I, Ghirarduzzi A, Legnani C, Gresele P, et al. Incidence of a first thromboembolic event in carriers of isolated lupus anticoagulant. Thromb Res. 2015;135(1):46–9.PubMed
83.
Posch F, Gebhart J, Rand JH, Koder S, Quehenberger P, Pengo V, et al. Cardiovascular risk factors are major determinants of thrombotic risk in patients with the lupus anticoagulant. BMC Med. 2017;15(1):54.PubMedPubMedCentral
84.
Zuo Y, Fan J, Sarode R, Zhang S, Makris UE, Karp DR, et al. Identifying additional risk factors for thrombosis and pregnancy morbidities among antiphospholipid antibodies carriers. Clin Appl Thromb. 2018;24(6):980–5.
85.
Panopoulos S, Thomas K, Georgiopoulos G, Boumpas D, Katsiari C, Bertsias G, et al. Comparable or higher prevalence of comorbidities in antiphospholipid syndrome vs rheumatoid arthritis: a multicenter, case-control study. Rheumatol Oxf Engl. 2021;60(1):170–8.
86.
Zuo Y, Udupa A, Fan J, Makris UE, Karp DR, Shen Y-M. The role of cardiovascular disease risk assessed by ASCVD score in primary thrombosis prophylaxis strategy among antiphospholipid antibody carriers. Lupus. 2018;27(13):2177–8.PubMedPubMedCentral
87.
Di Minno MND, Scalera A, Tufano A, Ambrosino P, Bettiol A, Silvestri E, et al. The association of adjusted Global AntiphosPholipid Syndrome Score (aGAPSS) with cardiovascular disease in subjects with antiphospholipid antibodies. Atherosclerosis. 2018;278:60–5.PubMed
88.
Tektonidou MG, Papassotiriou I, Sfikakis PP. Growth Differentiation Factor 15 (GDF-15) as potential cardiovascular risk biomarker in Antiphospholipid Syndrome. Rheumatol Oxf Engl. 2021;keab277.
89.
Tektonidou MG, Ward MM. Validity of clinical associations of biomarkers in translational research studies: the case of systemic autoimmune diseases. Arthritis Res Ther. 2010;12(5):R179.PubMedPubMedCentral
90.
Cohen H, Cuadrado MJ, Erkan D, Duarte-Garcia A, Isenberg DA, Knight JS, et al. 16th International Congress on Antiphospholipid Antibodies Task Force Report on Antiphospholipid Syndrome Treatment Trends. Lupus. 2020;29(12):1571–93. This task force report summarizes the novel treatment trends on antiphospholipid syndrome and identifies gaps in the literature to guide future researchPubMedPubMedCentral
91.
Pengo V, Denas G, Zoppellaro G, Jose SP, Hoxha A, Ruffatti A, et al. Rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome. Blood. 2018;132(13):1365–71.PubMed
92.
93.
Fazili M, Stevens SM, Woller SC. Direct oral anticoagulants in antiphospholipid syndrome with venous thromboembolism: Impact of the European Medicines Agency guidance. Res Pract Thromb Haemost. 2019;4(1):9–12.PubMedPubMedCentral
94.
Zuily S, Cohen H, Isenberg D, Woller SC, Crowther M, Dufrost V, et al. Use of direct oral anticoagulants in patients with thrombotic antiphospholipid syndrome: Guidance from the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. J Thromb Haemost JTH. 2020;18(9):2126–37. Guidelines about the use of direct oral anticoagulants in APS.PubMed
95.
Keeling D, Mackie I, Moore GW, Greer IA, Greaves M. British Committee for Standards in Haematology. Guidelines on the investigation and management of antiphospholipid syndrome. Br J Haematol. 2012;157(1):47–58.PubMed
96.
Arachchillage DRJ, Gomez K, Alikhan R, Anderson JAM, Lester W, Laffan M, et al. Addendum to British Society for Haematology Guidelines on Investigation and Management of Antiphospholipid syndrome, 2012 (Br. J. Haematol. 2012; 157: 47–58): use of direct acting oral anticoagulants. Br J Haematol. 2020;189(2):212–5.
97.
Kearon C, Parpia S, Spencer FA, Baglin T, Stevens SM, Bauer KA, et al. Antiphospholipid antibodies and recurrent thrombosis after a first unprovoked venous thromboembolism. Blood. 2018;131(19):2151–60.PubMedPubMedCentral
98.
Miranda S, Park J, Le Gal G, Piran S, Kherani S, Rodger MA, et al. Prevalence of confirmed antiphospholipid syndrome in 18–50 years unselected patients with first unprovoked venous thromboembolism. J Thromb Haemost JTH. 2020;18(4):926–30.PubMed
99.
Cohen H, Hunt BJ, Efthymiou M, Arachchillage DRJ, Mackie IJ, Clawson S, 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. 2016;3(9):e426-436.PubMedPubMedCentral
100.
Ordi-Ros J, Sáez-Comet L, Pérez-Conesa M, Vidal X, Riera-Mestre A, Castro-Salomó A, et al. Rivaroxaban versus vitamin K antagonist in antiphospholipid syndrome: a randomized noninferiority trial. Ann Intern Med. 2019;171(10):685–94.PubMed
101.
Legault K, Blostein M, Carrier M, Kahn S, Schulman S, Shivakumar S, et al. A single-arm feasibility cohort study of rivaroxaban in antiphospholipid syndrome. Pilot Feasibility Stud. 2020;6(1):52.PubMedPubMedCentral
102.
Pengo V, Hoxha A, Andreoli L, Tincani A, Silvestri E, Prisco D, et al. Trial of Rivaroxaban in AntiPhospholipid Syndrome (TRAPS): two-year outcomes after the study closure. J Thromb Haemost JTH. 2021;19(2):531–5. This 2-year follow-up to the TRAPS trial reported a higher rate of thrombotic events in the rivaroxaban study arm.PubMed
103.
Kravvariti E, Koutsogianni A, Evangelia Samoli E, Sfikakis PP, Tektonidou MG. The effect of hydroxychloroquine on thrombosis prevention and antiphospholipid antibody levels in primary antiphospholipid syndrome: A pilot open label randomized prospective study. Autoimmun Rev. 2020;19:102491. This is the first RCT examining the role of HCQ as adjunctive treatment in APS.
104.
Cohen H, Isenberg DA. How I treat anticoagulant-refractory thrombotic antiphospholipid syndrome. Blood. 2021;137(3):299–309.PubMed
105.
Tektonidou MG, Andreoli L, Limper M, Tincani A, Ward MM. Management of thrombotic and obstetric antiphospholipid syndrome: a systematic literature review informing the EULAR recommendations for the management of antiphospholipid syndrome in adults. RMD Open. 2019;5(1):e000924. This systematic review of the literature updated the knowledge on APS treatment and identified the heterogeneity of patient populations in available studies
106.
Xourgia E, Tektonidou MG. Management of non-criteria manifestations in antiphospholipid syndrome. Curr Rheumatol Rep. 2020;22(9):51.PubMed
107.
Erkan D, Vega J, Ramón G, Kozora E, Lockshin MD. A pilot open-label phase II trial of rituximab for non-criteria manifestations of antiphospholipid syndrome. Arthritis Rheum. 2013;65(2):464–71.PubMed
108.
Chatzidionysiou K, Samoli E, Sfikakis PP, Tektonidou MG. Effect of belimumab treatment on antiphospholipid antibody levels: post-hoc analysis based on two randomised placebo-controlled trials in systemic lupus erythematosus. Ann Rheum Dis. 2020;79(2):304–7.PubMed
109.
Bettiol A, Pregnolato F, Sciascia S, et al. Association of subcutaneous belimumab and long- term antimalarial treatment reduces antiphospholipid antibodies levels in systemic lupus erythematosus: post- hoc analysis of a randomised placebo- controlled trial—comment on: ’Effect of belimumab treatment on antiphospholipid antibody levels: post- hoc analysis based on two randomised placebo controlled trials in systemic lupus erythematosus’ by Chatzidionysiou et al. Ann Rheum Dis 2020.
110.
Sciascia S, Radin M, Ramirez C, Seaman A, Bentow C, Casas S, et al. Evaluation of novel assays for the detection of autoantibodies in antiphospholipid syndrome. Autoimmun Rev. 2020;19(10):102641.PubMed
111.
Ortel TL, Meleth S, Catellier D, Crowther M, Erkan D, Fortin PR, et al. Recurrent thrombosis in patients with antiphospholipid antibodies and an initial venous or arterial thromboembolic event: a systematic review and meta-analysis. J Thromb Haemost JTH. 2020;18(9):2274–86.PubMed
112.
Rodriguez-Pintó I, Espinosa G, Cervera R. Precision medicine and the antiphospholipid syndrome: what is the future? Clin Rheumatol. 2020;39(4):1015–7.PubMed
113.
Dobrowolski C, Erkan D. Treatment of antiphospholipid syndrome beyond anticoagulation. Clin Immunol Orlando Fla. 2019;206:53–62.
114.
Andrade D, Tektonidou M. Emerging therapies in antiphospholipid syndrome. Curr Rheumatol Rep. 2016;18(4):22.PubMed
Metadata
Title
An Update on Antiphospholipid Syndrome
Authors
Eleni Xourgia
Maria G. Tektonidou
Publication date
01-12-2021
Publisher
Springer US
Published in
Current Rheumatology Reports / Issue 12/2021
Print ISSN: 1523-3774
Electronic ISSN: 1534-6307
DOI
https://doi.org/10.1007/s11926-021-01051-5

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits