Management of patients with antiphospholipid antibodies: what to do in laboratory scenarios that do not fit the guidelines

References

• Miyakis S, Lockshin MD, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006 Feb;4(2):295–306.
   PubMed Web of Science ®Google Scholar
• Brandt JT, Triplett DA, Alving B, et al. Criteria for the diagnosis of lupus anticoagulants: an update. On behalf of the Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the ISTH. Thromb Haemost. 1995 Oct;74(4):1185–1190.
   PubMed Web of Science ®Google Scholar
• Tektonidou MG, Andreoli L, Limper M, et al. EULAR recommendations for the management of antiphospholipid syndrome in adults. Ann Rheum Dis. 2019 Oct;78(10):1296–1304.
   PubMed Web of Science ®Google Scholar
• Sammaritano LR, Bermas BL, Chakravarty EE, et al. American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases. Arthritis Rheumatol. 2020;72(4):529–556.
   PubMed Web of Science ®Google Scholar
• Zuo Y, Shi H, Li C, et al. Antiphospholipid syndrome: a clinical perspective. Chin Med J (Engl). 2020 Apr 20;133(8):929–940.
   PubMed Web of Science ®Google Scholar
• Rodziewicz M, D’Cruz DP. An update on the management of antiphospholipid syndrome. Ther Adv Musculoskelet Dis. 2020;12:1759720X20910855.
   PubMed Web of Science ®Google Scholar
• Ghembaza A, Saadoun D. Management of Antiphospholipid Syndrome. Biomedicines. 2020 Nov 17;8(11). 10.3390/biomedicines8110508.
   PubMed Web of Science ®Google Scholar
• Radin M, Cecchi I, Rubini E, et al. Treatment of antiphospholipid syndrome. Clin Immunol. 2020 Dec;221:108597.
   PubMed Web of Science ®Google Scholar
• Rahman A. Management of antiphospholipid syndrome. Clin Rheumatol. 2020;39(7):2111–2114.
   PubMed Web of Science ®Google Scholar
• Uthman I, Noureldine MHA, Ruiz-Irastorza G, et al. Management of antiphospholipid syndrome. Ann Rheum Dis. 2019 Feb;78(2):155–161.
   PubMed Web of Science ®Google Scholar
• Espinosa G, Cervera R. Current treatment of antiphospholipid syndrome: lights and shadows. Nat Rev Rheumatol. 2015 Oct;11(10):586–596.
   PubMed Web of Science ®Google Scholar
• Garcia D, D. E, Longo DL. Diagnosis and Management of the Antiphospholipid Syndrome. N Engl J Med. 2018;378(21):2010–2021.
   PubMed Web of Science ®Google Scholar
• Xourgia E, Tektonidou MG. Management of Non-criteria Manifestations in Antiphospholipid Syndrome.Curr Rheumatol Rep. 2020 ;22(9):51.
   PubMed Web of Science ®Google Scholar
• Cervera R, Conti F, Doria A, et al. Does seronegative antiphospholipid syndrome really exist? Autoimmun Rev. 2012 Jun;11(8):581–584.
   PubMed Web of Science ®Google Scholar
• Nayfe R, Uthman I, Aoun J, et al. Seronegative antiphospholipid syndrome. Rheumatology (Oxford). 2013 Aug;52(8):1358–1367.
   PubMed Web of Science ®Google Scholar
• Conti F, Capozzi A, Truglia S, et al. The mosaic of “seronegative” antiphospholipid syndrome. J Immunol Res. 2014;2014:389601.
   PubMed Web of Science ®Google Scholar
• Sciascia S, Radin M, Bazzan M, et al. Novel diagnostic and therapeutic frontiers in thrombotic anti-phospholipid syndrome. Intern Emerg Med. 2017;12(1):1–7.
   PubMed Web of Science ®Google Scholar
• Pignatelli P, Ettorre E, Menichelli D, et al. Seronegative antiphospholipid syndrome: refining the value of non-criteria antibodies for the diagnosis and clinical management. Haematologica. haematol. 2020;2019:221945.
   Google Scholar
• Zohoury N, Bertolaccini ML, Rodriguez-Garcia JL, et al. Closing the Serological Gap in the Antiphospholipid Syndrome: the Value of “Non-criteria” Antiphospholipid Antibodies. J Rheumatol. 2017;44(11):1597–1602.
   PubMed Web of Science ®Google Scholar
• Sciascia S, Radin M, Baldovino S, et al. Filling the gap in antiphospholipid syndrome diagnosis: a patient’s story. In: Graham RV Hughes (editor). Lupus.  United Kingdom: SAGE Publications2020. p. 961203320903810.
   Google Scholar
• Devreese KMJ, De Groot PG, De Laat B, et al. Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis. J Thromb Haemost. 2020;18(11):2828–2839.
   PubMed Web of Science ®Google Scholar
• Devreese KM. Antiphospholipid antibody testing and standardization. Int J Lab Hematol. 2014 Jun;36(3):352–363.
   PubMed Web of Science ®Google Scholar
• Meroni PL, Chighizola CB, Gerosa M, et al. Obstetric antiphospholipid syndrome: lobsters only? Or should we also look for selected red herrings? [Editorial]. The Journal of Rheumatology. 2015;42(2):158–160.
   PubMed Web of Science ®Google Scholar
• Galli M. Improving management of pregnancy in antiphospholipid antibody-positive women. J Rheumatol. 2006;33(11):2108–2109.
   PubMed Web of Science ®Google Scholar
• Ruffatti A, Favaro M, Calligaro A, et al. Management of pregnant women with antiphospholipid antibodies. Expert Rev Clin Immunol. 2019;15(4):347–358.
   PubMed Web of Science ®Google Scholar
• Bricker L. Types of pregnancy loss in recurrent miscarriage: implications for research and clinical practice. Hum Reprod. 2002;17(5):1345–1350.
   PubMed Web of Science ®Google Scholar
• Tan BE, Thong BYH, Shivananda S, et al. Clinical manifestations and outcomes of antithrombotic treatment of the Tan Tock Seng Hospital Singapore antiphospholipid syndrome cohort. Lupus. 2009;18(8):752–758.
   PubMed Web of Science ®Google Scholar
• Ruffatti A, Olivieri S, Tonello M, et al. Influence of different IgG anticardiolipin antibody cut-off values on antiphospholipid syndrome classification. J Thromb Haemost. 2008 Oct;6(10):1693–1696.
   PubMed Web of Science ®Google Scholar
• Ofer-Shiber S, Molad Y. Frequency of vascular and pregnancy morbidity in patients with low vs. moderate-to-high titers of antiphospholipid antibodies. Blood Coagul Fibrinolysis. 2015;26(3):261–266.
   PubMed Web of Science ®Google Scholar
• Stojanovich L, Markovic O, Marisavljevic D, et al. Influence of antiphospholipid antibody levels and type on thrombotic manifestations: results from the Serbian National Cohort Study. Lupus. 2012;21(3):338–345.
   PubMed Web of Science ®Google Scholar
• Ruiz-Irastorza G, Hunt BJ, Khamashta MA. A systematic review of secondary thromboprophylaxis in patients with antiphospholipid antibodies. Arthritis Rheum. 2007 Dec 15;57(8):1487–1495.
   PubMed Web of Science ®Google Scholar
• Laskin CA, Spitzer KA, Clark CA, et al. Low molecular weight heparin and aspirin for recurrent pregnancy loss: results from the randomized, controlled HepASA Trial. J Rheumatol. 2009 Feb;36(2):279–287.
   PubMed Web of Science ®Google Scholar
• Pattison NS, Chamley LW, Birdsall M, et al. Does aspirin have a role in improving pregnancy outcome for women with the antiphospholipid syndrome? A randomized controlled trial. Am J Obstet Gynecol. 2000 Oct;183(4):1008–1012.
   PubMed Web of Science ®Google Scholar
• Merrill JT. Appropriate management of antiphospholipid-related pregnancy in women without lupus who have low titer autoantibodies. Curr Rheumatol Rep. 2001 Aug;3(4):269–270.
   PubMedGoogle Scholar
• Del Ross T, Ruffatti A, Visentin MS, et al. Treatment of 139 pregnancies in antiphospholipid-positive women not fulfilling criteria for antiphospholipid syndrome: a retrospective study. J Rheumatol. 2013 Apr;40(4):425–429.
   PubMed Web of Science ®Google Scholar
• Mekinian A, Loire-Berson P, Nicaise-Roland P, et al. Outcomes and treatment of obstetrical antiphospholipid syndrome in women with low antiphospholipid antibody levels. J Reprod Immunol. 2012 Jun;94(2):222–226.
   PubMed Web of Science ®Google Scholar
• Alijotas-Reig J, Esteve-Valverde E, Ferrer-Oliveras R, et al. Comparative study of obstetric antiphospholipid syndrome (OAPS) and non-criteria obstetric APS (NC-OAPS): report of 1640 cases from the EUROAPS registry. Rheumatology (Oxford). 2020 Jun 1;59(6):1306–1314.
   PubMed Web of Science ®Google Scholar
• Alijotas-Reig J, Esteve-Valverde E, Ferrer-Oliveras R, et al. Comparative study between obstetric antiphospholipid syndrome and obstetric morbidity related with antiphospholipid antibodies. Med Clin (Barc). 2018 Sep 21;151(6):215–222.
   PubMed Web of Science ®Google Scholar
• Alijotas-Reig J, Esteve-Valverde E, Ferrer-Oliveras R, et al. Comparative study of obstetric antiphospholipid syndrome (OAPS) and non-criteria obstetric APS (NC-OAPS): report of 1640 cases from the EUROAPS registry. Rheumatology (Oxford). 2019 Oct 3.
   Google Scholar
• Li X, Deng X, Duan H, et al. Clinical features associated with pregnancy outcomes in women with positive antiphospholipid antibodies and previous adverse pregnancy outcomes: a real-world prospective study. Clin Rheumatol. 2021;40(1):193-204.
   Web of Science ®Google Scholar
• Sugiura-Ogasawara M, Ozaki Y, Nakanishi T, et al. Occasional antiphospholipid antibody positive patients with recurrent pregnancy loss also merit aspirin therapy: a retrospective cohort-control study. Am J Reprod Immunol. 2008 Mar;59(3):235–241.
   PubMed Web of Science ®Google Scholar
• Lo HW, Chen CJ, Tsai EM. Pregnancy outcomes for women with non-criteria antiphospholipid syndrome after anticoagulant therapy. Eur J Obstet Gynecol Reprod Biol. 2020 Jan;244:205–207.
   PubMed Web of Science ®Google Scholar
• Pregnolato F, Gerosa M, Raimondo MG, et al., EUREKA algorithm predicts obstetric risk and response to treatment in women with different subsets of anti-phospholipid antibodies. United Kingdom: Rheumatology (Oxford). 2020 May. p. 22.
   Google Scholar
• Funke A, Staub HL, Monticielo OA, et al. Non-criteria Antiphospholipid Antibodies: a narrative review. Revista Da Associação Médica Brasileira. 2020;66(11):1595–1601.
   PubMed Web of Science ®Google Scholar
• Sciascia S, Sanna G, Murru V, 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. 2014;111(2):354–364.
   PubMed Web of Science ®Google Scholar
• Sciascia S, Sanna G, Murru V, et al. GAPSS: the Global Anti-Phospholipid Syndrome Score. Rheumatology. 2013;52(8):1397–1403.
   PubMed Web of Science ®Google Scholar
• Volkov I, Seguro L, Leon EP, 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.
   PubMed Web of Science ®Google Scholar
• Mekinian A, Bourrienne MC, Carbillon L, et al. Non-conventional antiphospholipid antibodies in patients with clinical obstetrical APS: prevalence and treatment efficacy in pregnancies. Semin Arthritis Rheum. 2016;46(2):232–237. Oct.
   PubMed Web of Science ®Google Scholar
• Abisror N, Nguyen Y, Marozio L, et al. Obstetrical outcome and treatments in seronegative primary APS: data from European retrospective study. RMD Open. 2020;6(2):e001340.
   Web of Science ®Google Scholar
• Pengo V, Ruffatti A, Del Ross T, et al. Confirmation of initial antiphospholipid antibody positivity depends on the antiphospholipid antibody profile. J Thromb Haemost. 2013;11(8):1527–1531.
   PubMed Web of Science ®Google Scholar
• Erkan D, Derksen W, Kaplan V, et al. Real world experience with antiphospholipid antibody tests: how stable are results over time? Annals of the Rheumatic Diseases. 2005;64(9):1321–1325.
   PubMed Web of Science ®Google Scholar
• Martinez-Berriotxoa A, Ruiz-Irastorza G, Egurbide MV, et al. Transiently positive anticardiolipin antibodies and risk of thrombosis in patients with systemic lupus erythematosus. Lupus. 2007;16(10):810–816.
   PubMed Web of Science ®Google Scholar
• Levine SR, Brey RL, Tilley BC, et al. Antiphospholipid antibodies and subsequent thrombo-occlusive events in patients with ischemic stroke. Jama. 2004;291(5):576–584.
   PubMed Web of Science ®Google Scholar
• Amory CF, Levine SR, Brey RL, et al. Antiphospholipid Antibodies and Recurrent Thrombotic Events: persistence and Portfolio. Cerebrovascular Dis. 2015;40(5–6):293–300.
   PubMed Web of Science ®Google Scholar
• Khawaja M, Magder L, Goldman D, et al. Loss of antiphospholipid antibody positivity post-thrombosis in SLE. Lupus Sci Med. 2020;7(1):1.
   Web of Science ®Google Scholar
• Medina G, Briones-García E, Cruz-Domínguez MP, et al. Antiphospholipid antibodies disappearance in primary antiphospholipid syndrome: thrombosis recurrence. Autoimmun Rev. 2017;16(4):352–354.
   PubMed Web of Science ®Google Scholar
• Riancho-Zarrabeitia L, Daroca G, Muñoz P, et al. Serological evolution in women with positive antiphospholipid antibodies. Semin Arthritis Rheum. 2017;47(3):397–402.
   PubMed Web of Science ®Google Scholar
• Radin M, Schreiber K, Sciascia S, et al. Prevalence of Antiphospholipid Antibodies Negativisation in Patients with Antiphospholipid Syndrome: a Long-Term Follow-Up Multicentre Study. Thrombosis and Haemostasis. 2019;119(12):1920–1926.
   PubMed Web of Science ®Google Scholar
• Girón-González JA, García Del Río E, Rodríguez C, et al. Antiphospholipid syndrome and asymptomatic carriers of antiphospholipid antibody: prospective analysis of 404 individuals. J Rheumatol. 2004;31(8):1560–1567.
   PubMed Web of Science ®Google Scholar
• Gkrouzman E, Sevim E, Finik J, et al. Antiphospholipid Antibody Profile Stability Over Time: prospective Results from APS ACTION Clinical Database and Repository. J Rheumatol. 2020:200513.
   Web of Science ®Google Scholar
• Criado-García J, Fernández-Puebla RA, Jiménez LL, et al. [Anticoagulation treatment withdrawal in primary antiphospholipid syndrome when anticardiolipin antibodies become negative]. Revista Clínica Española. 2008;208(3):135–137.
   PubMed Web of Science ®Google Scholar
• Coloma Bazán E, Donate López C, Moreno Lozano P, et al. Discontinuation of anticoagulation or antiaggregation treatment may be safe in patients with primary antiphospholipid syndrome when antiphospholipid antibodies became persistently negative. Immunologic Research. 2013;56(2–3):358–361.
   PubMed Web of Science ®Google Scholar
• Comarmond C, Jego P, Veyssier-Belot C, et al. Cessation of oral anticoagulants in antiphospholipid syndrome. Lupus. 2017;26(12):1291–1296.
   PubMedGoogle Scholar
• Hindilerden F, Yonal-Hindilerden I, Could D-KR. Anticoagulation or Antiaggregation Treatment Be Ceased in Patients With Primary Antiphospholipid Syndrome When Antiphospholipid Antibodies Become Persistently Negative? JCR: J Clinic Rheumatol. 2017;23:6.
   PubMed Web of Science ®Google Scholar
• Yelnik CM, Urbanski G, Drumez E, et al. Anticoagulation withdrawal in antiphospholipid syndrome: a retrospective matched-control study. Lupus. 2018;27(3):357–364.
   PubMed Web of Science ®Google Scholar
• Zen M, Loredo Martinez M, Benvenuti F, et al. Prevalence, outcome and management of patients with SLE and secondary antiphospholipid antibody syndrome after aPL seroconversion. Rheumatology 2021;60(3):1313-1320.
   Web of Science ®Google Scholar
• Skeith L, Bates SM, Bates V, et al. The challenges and lessons learned in conducting clinical trials in pregnant women with antiphospholipid syndrome. Thrombosis Research. 2020;194(194):54–56.
   PubMedGoogle Scholar
• Ramires De Jesús G, Levy RA, Porter TF, et al. Limited evidence for diagnosing and treating “non-criteria obstetric antiphospholipid syndrome”. Thromb Haemost. 2015 Aug 31;114(3):651–652.
   PubMed Web of Science ®Google Scholar
• De Jesús GR, Benson AE, Chighizola CB, et al. 16th International Congress on Antiphospholipid Antibodies Task Force Report on Obstetric Antiphospholipid Syndrome. Lupus. 2020;29(12):1601–1615.
   PubMedGoogle Scholar
• Abdel-Wahab N, Lopez-Olivo MA, Pinto-Patarroyo GP, et al. Systematic review of case reports of antiphospholipid syndrome following infection. Lupus. 2016;25(14):1520–1531.
   PubMed Web of Science ®Google Scholar
• Dlott JS, Roubey RA. Drug-induced lupus anticoagulants and antiphospholipid antibodies. Current Rheumatology Reports. 2012;14(1):71–78.
   PubMed Web of Science ®Google Scholar
• Vassalo J, Spector N, De Meis E, et al. Antiphospholipid antibodies in critically ill patients with cancer: a prospective cohort study. Journal of Critical Care. 2014;29(4):533–538.
   PubMed Web of Science ®Google Scholar
• Alijotas-Reig J. Does incomplete obstetric antiphospholipid syndrome really exist? Med Clin (Barc). 2021(Feb):22.
   PubMedGoogle Scholar
• Bouvier S, Cochery-Nouvellon E, Lavigne-Lissalde G, et al. Comparative incidence of pregnancy outcomes in treated obstetric antiphospholipid syndrome: the NOH-APS observational study. Blood. 2014 Jan 16;123(3):404–413.
   PubMed Web of Science ®Google Scholar
• Ruffatti A, Tonello M, Visentin MS, et al. Risk factors for pregnancy failure in patients with anti-phospholipid syndrome treated with conventional therapies: a multicentre, case-control study. Rheumatology (Oxford). 2011;50(9):1684–1689.
   PubMed Web of Science ®Google Scholar
• Lockshin MD, Kim M, Laskin CA, et al. Prediction of adverse pregnancy outcome by the presence of lupus anticoagulant, but not anticardiolipin antibody, in patients with antiphospholipid antibodies. Arthritis & Rheumatism. 2012;64(7):2311–2318.
   PubMed Web of Science ®Google Scholar
• Misasi R, Longo A, Recalchi S, et al. Molecular Mechanisms of “Antiphospholipid Antibodies” and Their Paradoxical Role in the Pathogenesis of “Seronegative APS”. International Journal of Molecular Sciences. 2020 Nov 9;21(21):21.
   Web of Science ®Google Scholar
• Diz-Kucukkaya R, Hancer VS, Artim-Esen B, et al. The prevalence and clinical significance of inherited thrombophilic risk factors in patients with antiphospholipid syndrome. Journal of Thrombosis and Thrombolysis. 2010;29(3):303–309.
   PubMed Web of Science ®Google Scholar
• Espinosa G, Cervera R. Thromboprophylaxis and obstetric management of the antiphospholipid syndrome. Expert Opin Pharmacother. 2009;10(4):601–614.
   PubMed Web of Science ®Google Scholar
• Alijotas-Reig J, Ferrer-Oliveras R, Esteve-Valverde E, et al. Inherited thrombophilia in women with poor aPL-related obstetric history: prevalence and outcomes. Survey of 208 cases from the European Registry on Obstetric Antiphospholipid Syndrome cohort. American Journal of Reproductive Immunology. 2016;76(2):164–171.
   PubMed Web of Science ®Google Scholar
• De Carolis S, Tabacco S, Rizzo F, et al. Antiphospholipid syndrome: an update on risk factors for pregnancy outcome. Autoimmun Rev. 2018;17(10):956–966.
   PubMed Web of Science ®Google Scholar
• Da Silva FF, Levy RA, De Carvalho JF. Cardiovascular Risk Factors in the Antiphospholipid Syndrome. J Immunol Res. 2014;2014:621270.
   PubMed Web of Science ®Google Scholar
• Sciascia S, Radin M, Sanna G, et al. Clinical utility of the global anti-phospholipid syndrome score for risk stratification: a pooled analysis. Rheumatology. 2018;57(4):661–665.
   PubMed Web of Science ®Google Scholar