Recently, recommendations for the management of antiphospholipid syndrome (APS) in adults were published by the European League Against Rheumatism based on evidence from a systematic literature review and expert opinion.1 The antiphospholipid antibody (aPL) type, the presence of multiple (double or triple) versus single aPL type, their titre (moderate-high titre versus low titre) and the persistence of aPL positivity in repeated measurements are defined as the ‘ aPL profile’. The aPL profile is an important factor determining the risk of thrombotic and obstetric events, and consequently the intensity of treatment. The presence of aPL in asymptomatic individuals or patients with systemic lupus erythematosus (SLE) does not confirm the diagnosis of APS but can be associated with increased risk of thrombosis or pregnancy morbidity, depending on aPL characteristics and coexistence of other risk factors.2 Low dose aspirin (LDA) is recommended for asymptomatic aPL carriers, patients with SLE without prior thrombotic or obstetric APS, and non-pregnant women with a history of obstetric APS only, all with high- risk aPL profile. Immunosuppressive drugs plus steroids do not protect against recurrent thrombosis in APS. Patients with APS and first unprovoked venous thrombosis should receive long-term treatment with vitamin k antagonists (VKA) with a target international normalized ratio (INR) of 2.0–3.0. In patients with APS, with first arterial thrombosis, treatment with VKA with INR 2.0–3.0 or 3.0–4.0 is recommended, considering the individual’s bleeding/thrombosis risk. In all cases treatment should be continued even if the patient becomes aPL negative. Direct oral anticoagulants (DOACs) could be considered in APS patients with venous thrombosis who are not able to achieve a target INR despite good adherence to VKA or those in whom VKA is contraindicated (e.g. allergy or intolerance to VKA).3 Rivaroxaban should not be used in patients with APS with triple aPL positivity.4 Based on the current evidence, the use of DOACs in patients with APS and arterial events is not recommended due to the high risk of recurrent thrombosis. For patients with recurrent arterial or venous thrombosis despite adequate treatment, addition of LDA, increase of INR target to 3.0–4.0 or switch to low molecular weight heparin may be considered. Other potential strategies for refractory APS cases include rituximab and hematopoietic stem cell transplantation. Thrombocytopenia is not rare in APS and is mostly mild, not requiring intervention. Bleeding is uncommon in these patients and it is important not to stop VKA therapy because low platelet counts do not protect against thrombosis. Careful monitoring is advocated for mild-moderate thrombocytopenia, and corticosteroids are recommended for severe cases. In women with prior obstetric APS, combination treatment with LDA and prophylactic dosage heparin during pregnancy is recommended. In patients with recurrent pregnancy complications, increased heparin to therapeutic dose, addition of hydroxychloroquine or addition of low dose prednisolone in the first trimester may be considered. Use of intravenous immunoglobulin might be considered in highly selected cases. Patients with APS still develop significant morbidity and mortality despite current treatment. It is imperative to increase the efforts in determining optimal prognostic markers and therapeutic measures to prevent these complications.5
Discuss data that support treatment decisions for APS
Tektonidou MG, Andreoli L, Limper M, et al. EULAR recommendations for the management of antiphospholipid syndrome in adults. Annals of the Rheumatic Diseases 2019:annrheumdis-2019–215213.
Uthman I, Noureldine MHA, Ruiz-Irastorza G, et al. Management of antiphospholipid syndrome. Ann Rheum Dis 2019;78(2):155–61.
Cohen H, Hunt BJ, Efthymiou M, 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. The Lancet Haematology 2016;3(9):e426–36.
Pengo V, Denas G, Zoppellaro G, et al. Rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome. Blood 2018;132(13):1365–71.
Cervera R, Serrano R, Pons-Estel GJ, 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.
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.