Elsevier

Autoimmunity Reviews

Volume 16, Issue 11, November 2017, Pages 1109-1114
Autoimmunity Reviews

Can we withdraw anticoagulation in patients with antiphospholipid syndrome after seroconvertion?

https://doi.org/10.1016/j.autrev.2017.09.004Get rights and content

Abstract

The current mainstay of treatment in patients with thrombotic antiphospholipid syndrome (APS) is long-term anticoagulation, mainly with Vitamin K antagonist agents. Some recently available studies have created new ground for discussion about the possible discontinuation of anticoagulation therapy in patients with a history of thrombotic APS in whom antiphospholipid antibodies (aPL) are not detected any longer (i.e. aPL seroconversion).

We report the main points discussed at the last CORA Meeting regarding the issue whether or not anticoagulation can be stopped after aPL seroconversion. In particular, we systematically reviewed the available evidence investigating the clinical outcome of APS patients with aPL seroconversion in whom anticoagulation was stopped when compared to those in whom therapy was continued regardless the aPL profile. Furthermore, the molecular basis for the aPL pathogenicity, the available evidence of non-criteria aPL and their association with thrombosis are addressed.

To date, available evidence is still limited to support the indication to stop oral anticoagulation therapy in patients with a previous diagnosis of thrombotic APS who subsequently developed a negative aPL profile. The identification of the whole risk profile for cardiovascular manifestations and possibly of a second level aPL testing in selected patients with aPL might support the eventual clinical decision but further investigation is warranted.

Introduction

High morbidity and mortality due to recurrence of thrombotic events is the main concern in patients with antiphospholipid syndrome (APS) [1]. Current evidence-based guidelines recommend long-term oral anticoagulation (OAC) as prophylaxis of new thrombotic manifestations of APS. The decision on the duration and intensity of this treatment should be based on the clinical features and immunological profile. According to the guidelines, patients with definite APS and a first venous thrombotic event should receive long-term OAC to an international normalized ratio (INR) target of 2.0–3.0 (the so called conventional-intensity anticoagulation). On the other side, patients with definite APS and an arterial thrombotic event should receive high-intensity anticoagulation therapy to an INR target between 3.0 and 4.0. However, long-term OAC has also been associated to a wide broad of hemorrhagic complications [2].

Especial attention has recently been payed to a small subset of patients who fulfill APS criteria but in whom aPL become persistently negative [3].

We systematically reviewed the available evidence investigating the clinical outcome of APS patients with aPL seroconversion (negativization) in whom anticoagulation was stopped when compared to those in whom therapy was continued regardless the aPL profile. Moreover, we aim to discuss the molecular basis for the aPL pathogenicity and the available evidence of non-criteria aPL and their association with thrombosis.

Section snippets

Systematic review of the available evidence on aPL seroconversion

The aim of this systematic review is to identify the available evidence on the clinical experience of thrombotic APS patients with persistent negative aPL. We also focused on those cases where anticoagulation was stopped after patients showed persistent negativity to conventional aPL tests.

Molecular basis for the antiphospholipid antibody pathogenicity

The underlying mechanisms by which aPL can induce a thrombophilic phenotype and clinical manifestations are still under investigation. In this section, we will review the available evidence on molecular basis for aPL pathogenicity based mainly on the studies carried out by a group of the authors of the present manuscript (SS, RM, BML, LPC, CMJ). The aim to review these mechanisms is to show the profound changes that aPL induces at different levels of coagulation and inflammatory pathways.

Non-classification criteria antiphospholipid antibodies and thrombosis

Data gathered in recent years explored the relationship between three groups of antiphospholipid antibodies, not currently included in the classification criteria and the development of thrombotic events. In this section, we will summarize available data on Prothrombin/phosphatidylserine complex, antibodies directed to the Domain I of β2GPI and IgA aPL, and their association with thrombotic risk.

Conclusions

aPL seroconversion and its definition is a rising topic of interest in the field of APS. Although there are reports in the literature supporting the discontinuation of antithrombotic treatment in some patients with primary APS in whom aPL became persistently negative, we still do not have enough data to make sound recommendation whether or not and when stopping oral anticoagulation therapy in APS patients with seroconversion.

In particular, there is concern about the changes induced by aPL in

Acknowledgments

None.

Disclosure of conflicts of interest

None declared.

Funding

None declared.

References (55)

  • R. Teruel et al.

    Identification of miRNAs as potential modulators of tissue factor expression in patients with systemic lupus erythematosus and antiphospholipid syndrome

    J Thromb Haemost

    (2011)
  • M.L. Bertolaccini et al.

    14th International Congress on Antiphospholipid Antibodies Task Force. Report on antiphospholipid syndrome laboratory diagnostics and trends

    Autoimmun Rev

    (2014)
  • S.W. Reddel et al.

    Epitope studies with anti-β2-glycoprotein I antibodies from autoantibody and immunized sources

    J Autoimmun

    (2000)
  • B. De Laat et al.

    IgG antibodies that recognize epitope Gly40-Arg43 in domain I of β2-glycoprotein I cause LAC, and their presence correlates strongly with thrombosis

    Blood

    (2005)
  • B. de Laat et al.

    The association between circulating antibodies against domain I of beta2-glycoprotein I and thrombosis: an international multicenter study

    J Thromb Haemost

    (2009)
  • A. Banzato et al.

    Antibodies to domain I of β2Glycoprotein I are in close relation to patients' risk categories in antiphospholipid syndrome (APS)

    Thromb Res

    (2011)
  • H. Meijide et al.

    The clinical relevance of IgA anticardiolipin and IgA anti-β2 glycoprotein I antiphospholipid antibodies: a systematic review

    Autoimmun Rev

    (2013)
  • R. Cervera 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)
  • G. Ruiz-Irastorza 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

    (2011)
  • M. Radin et al.

    Antiphospholipid antibodies negativization: time for testing for non-criteria aPL?

    Lupus

    (2017)
  • C. Comarmond et al.

    Cessation of oral anticoagulants in antiphospholipid syndrome

    (2017)
  • E. Coloma Bazán et al.

    Discontinuation of anticoagulation or antiaggregation treatment may be safe in patients with primary antiphospholipid syndrome when antiphospholipid antibodies became persistently negative

    Immunol Res

    (2013)
  • M.J. Cuadrado et al.

    Thrombosis in primary antiphospholipid syndrome: a pivotal role for monocyte tissue factor expression

    Arthritis Rheum

    (1997)
  • C. López-Pedrera et al.

    Antiphospholipid syndrome and tissue factor: a thrombotic couple

    Lupus

    (2006)
  • S. Dunoyer-Geindre et al.

    NFkappaB is an essential intermediate in the activation of endothelial cells by anti-beta(2)-glycoprotein 1 antibodies

    Thromb Haemost

    (2002)
  • M. Vega-Ostertag et al.

    Intracellular events in platelet activation induced by antiphospholipid antibodies in the presence of low doses of thrombin

    Arthritis Rheum

    (2004)
  • M. Bohgaki et al.

    The p38 mitogen-activated protein kinase (MAPK) pathway mediates induction of the tissue factor gene in monocytes stimulated with human monoclonal anti-beta2Glycoprotein I antibodies

    Int Immunol

    (2004)
  • Cited by (0)

    1

    Sciascia S, Coloma-Bazán E contributed equally to this work.

    2

    Cervera R, Cuadrado MJ contributed equally to this work.

    View full text