The antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by recurrent thrombosis and/or obstetrical morbidity in the presence of persistently positive antiphospholipid antibodies. Recent insights into the pathogenesis of APS have begun to elucidate pathophysiology and led to the identification of potential therapeutic interventions. The objective of this review is to examine the advances in this field and highlight the areas of further investigation.
Several mechanisms of thrombosis and pregnancy loss in APS have been proposed. These include activation of endothelial cells, monocytes, and platelets, and/or inhibition of natural anticoagulant and fibrinolytic systems by antiphospholipid antibodies. However, in many cases the underlying molecular mechanisms and their relevance to the human disorder remain uncertain. New therapeutic agents such as statins, hydroxychloroquine, rituximab, complement inhibitors, and interventions aimed at disruption of intracellular signaling pathways have shown promise in preclinical and clinical studies.
Indefinite anticoagulation remains the mainstay of treatment for thrombotic APS. Despite advances in diagnostic techniques, it remains difficult to predict thrombotic risk in asymptomatic patients with antiphospholipid antibodies. Further mechanistic and clinical studies are needed to predict thrombotic risk and develop improved therapies for this devastating illness.
aDepartment of Internal Medicine
bTaussig Cancer Institute
cDepartment of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, Ohio, USA
Correspondence to Keith R. McCrae, MD, Taussig Cancer Institute, R4-018, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA. Tel: +1 216 445 7809; fax: +1 216 445 7809; e-mail: firstname.lastname@example.org