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Antiphospholipid syndrome

https://doi.org/10.1016/j.berh.2016.04.002Get rights and content

Abstract

Antiphospholipid syndrome (APS) is an autoimmune condition characterized by the occurrence of thrombosis (arterial and/or venous), often multiple, and/or pregnancy morbidity.

Thrombosis is one of the major disease mechanisms, mainly caused by activating endothelial cells, monocytes, and platelets. At present, the management of APS patients with a history of thrombosis is based on long-term antithrombotic therapy, due to the high rate of recurrent thrombosis (29% per year without treatment). Obstetrical APS includes heterogeneous pregnancy complications whose pathogenesis has been increasingly elucidated in the past years. This is due to the current management and treatment, as 80% of APS patients achieve a live birth. The standard approach of APS is not supported by extensive evidence and the best options for refractory and incomplete cases need to be clarified. New and promising molecules are under investigation.

Introduction

Antiphospholipid syndrome (APS) is an autoimmune condition characterized by the occurrence of thrombosis (arterial and/or venous), often multiple, and/or morbidity in pregnancy (recurrent miscarriages, fetal deaths (FDs), and late pregnancy complications such as preeclampsia (PreE) and intrauterine growth restriction (IUGR)), in the presence of antiphospholipid antibodies (aPLs), typically the antibodies included in the classification criteria for APS, lupus anticoagulant (LA), anticardiolipin (aCL), or anti-β2 glycoprotein-I (anti-β2GPI) antibodies (Table 1), although other “non-criteria” antibodies may also play a role. APS may be associated with other autoimmune diseases, mainly systemic lupus erythematosus (SLE), but it can also be seen in patients having no other definable rheumatologic condition (primary APS). Occasionally, it can accompany other conditions, such as infections, drugs, or malignancies [1].

In this review, we discuss recent advances in the diagnosis of APS including new insights into the pathogenesis and the implications for the identification of new biomarkers. In addition, the importance of recent longitudinal observational studies in understanding the natural history of the syndrome and for embedding research in clinical practice will be elucidated.

Section snippets

Pathogenesis

Although the full pathogenesis of APS is not yet clear, the key mechanisms have been described recently. Thrombosis is one of the major disease features, driven by multiple mechanisms including activation of endothelial cells, monocytes, platelets, coagulation, and complement pathways in addition to inhibition of fibrinolytic and anticoagulation pathways [2]. Recent evidence indicates that vasculopathy, enhanced mainly by severe intimal hyperplasia, can also play a role in arterial vascular

Pathogenesis

The pathogenic role of aPLs in obstetrical APS (OAPS) was initially demonstrated by experimental models showing that the passive transfer of IgG isotype aPLs could induce FD and IUGR in pregnant mice [56]. Three mechanisms for aPL-induced pregnancy morbidity have been postulated: intraplacental thrombosis, defective placentation, and inflammation.

Intraplacental thrombosis and the subsequent alteration of maternal–fetal blood exchanges were thought to be the main pathogenic mechanism of OAPS for

Future research agenda

Despite advances in the understanding of APS in recent years, many areas need to be investigated further. Although it seems imperative to increase the efforts in determining optimal prognostic markers and therapeutic measures to prevent APS complications, difficulties in conducting randomized control trials in the setting of a relatively rare condition still remain. Well-designed longitudinal observational multicenter studies, such as prospective registries, using agreed classification

Summary

There have been many advances in the understanding of APS in recent years, but many areas need to be further investigated in particular the association between autoantibodies and clinical manifestations, the identification of high-risk patients, the best treatment for each patient category, and the role of new therapeutic strategies. Well-designed longitudinal observational multicenter studies, such as prospective registries, using classification criteria, validated outcome measures, and

Conflict of interest

None.

Acknowledgments

None.

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