The antiphospholipid syndrome as a disorder initiated by inflammation: implications for the therapy of pregnant patients

Abstract

Arterial thrombosis, venous thrombosis and morbidity during pregnancy, or a combination of these events, are clinical outcomes associated with antiphospholipid antibodies produced by patients with antiphospholipid syndrome (APS). Our understanding of the etiology and pathogenesis of the syndrome is limited, but it has generally been considered a thrombophilic disease and treatment has focused on anticoagulation. Agents such as aspirin and heparin, administered alone or in combination, are empirical treatments that are used in the management of obstetric patients with APS. Clinical features, such as heart valve abnormalities, thrombocytopenia and livedo reticularis, suggest multiple pathogenic mechanisms and provide other therapeutic targets. Findings from research in animal models of APS challenge the dogma that this syndrome is a noninflammatory, thrombotic disease and provide evidence that activation of complement is crucial for complications in pregnancy. These studies, in addition to evidence of inflammatory-mediated tissue damage in placentae of patients with APS, suggest that therapy should also be directed towards preventing inflammation. This Review describes the potential mechanisms of tissue injury by antiphospholipid antibodies, the management of pregnant patients with APS and how heparin therapy might inhibit the pathogenic mediators of disease.