Comment on: EULAR recommendations for the management of antiphospholipid syndrome in adults. Tektonidou MG, et al. Ann Rheum Dis. 2019;78:1296-1304.
Commented by: Maria G. Tektonidou, MD, PhD, Associate Professor of Rheumatology. Head of Rheumatology Unit, First Department of Propaedeutic Internal Medicine, School of Medicine, University of Athens, Greece
Due to the rarity of Antiphospholipid syndrome (APS), its complex pathogenesis, heterogeneous clinical presentation  and the lack of high- quality randomized clinical trials, the formulation of guidelines for the management of APS has been both a dire necessity and a difficult task. “EULAR recommendations for the management of APS in adults” were developed to address this issue, aiming to provide evidence-based recommendations for APS stemming from a combination of expert opinion and a systematic review of the relevant literature. A task force comprised of specialists from 11 European countries tackled four pivotal questions regarding the prevention and treatment of different forms of APS: risk stratification and modification in asymptomatic individuals with positive antiphospholipid antibodies (aPL), primary and secondary prevention of thrombosis in APS, management of obstetric APS, and catastrophic APS (CAPS) treatment .
The qualitative and quantitative characterization of aPL such as their type, single-, double- or triple-positivity, titer, and persistence of positivity in repeat measurements formulate the “aPL profile”. Stratification of patients into those having low- and high-risk aPL profiles is considered as one of the main pillars on which the varying recommendations are based. Proposed risk attenuation measures are comprised of lifestyle modifications, emphasizing the importance of treatment adherence and eliminating cardiovascular and venous thrombosis risk factors .
As far as pharmacological treatment of APS is concerned, different substances including low-dose aspirin (LDA), vitamin K antagonists (VKA), heparin, hydroxychloroquine (HCQ) or immunosuppressive agents can be used variably in accordance to each different clinical scenario. Administration of LDA is recommended for asymptomatic aPL carriers, patients with SLE without history of thrombotic or obstetric APS, and non-pregnant women with prior obstetric APS, if high-risk aPL profiles are present. Patients with first unprovoked venous thrombosis should receive VKA with a target international normalized ratio (INR) of 2-3, while in those with first arterial thrombosis VKA treatment of a target INR of 2-3 or 3-4 can be considered, according to each individual bleeding/thrombosis risk.
In patients with recurrent thrombotic events despite an appropriate treatment, either adding LDA to the treatment regimen, increasing the target INR to 3-4 or using low molecular weight heparin are effective alternatives [2, 3]. Use of direct oral anticoagulants (DOACs) is not recommended in patients with a history of vascular thrombosis and triple aPL positivity. In pregnant women with prior obstetric APS, prophylactic dose of heparin should be used in conjunction with LDA. In women with recurring pregnancy complications despite a combination treatment with prophylactic dose heparin and low dose aspirin, therapeutic dose of heparin plus LDA, or add-on therapy with either HCQ or low-dose prednisone during the first trimester, are appropriate treatment options. First line treatment of CAPS includes a combination therapy with glucocorticoids, heparin and plasma exchange or intravenous immunoglobulins.
Following the formulation of the current recommendations for APS in adults, an emerging need for more high-quality studies is evident. To this end, a plan in the form of a research agenda has been drafted by the task force, underlining the main points on which future studies should be focused. These points include a better stratification by risk in order to avoid over- or under-treatment, as well as emerging treatments including HCQ use in primary and secondary thrombosis prevention and obstetric APS, statins, other platelet inhibitors, and targeted treatments (e.g. B-cell depletion, complement inhibition or mTOR inhibition).
Further clarification of the pathogenetic mechanisms of APS along with studies focusing on how the different phenotypes of the syndrome may respond to various treatment types are necessary in order to facilitate the expansion and improvement of the current recommendations so as to achieve better quality of care for individuals with APS.
- Miyakis S, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006;4:295–306
- Tektonidou MG, et al. EULAR recommendations for the management of antiphospholipid syndrome in adults. Ann Rheum Dis. May 2019:annrheumdis-2019-215213.
- 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 Apr 28;5(1):e000924.