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.
Arthritis Research & Therapy 09/2012; 14(3). DOI:10.1186/ar3967 · 4.12 Impact Factor
Arthritis Research & Therapy 09/2012; 14(3). DOI:10.1186/ar3968 · 4.12 Impact Factor
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ABSTRACT: Miscarriage and thrombosis are important causes of morbidity and mortality in patients with the antiphospholipid (Hughes) syndrome. However, the precise mechanism responsible for these complications remains unclear. Among the different immunity-related components that could be implicated in the pathogenesis of this systemic autoimmune disease, immunophenotypic abnormalities in peripheral blood lymphocytes have rarely been sought. We review studies that have been designed to assess functionally distinct T, B, and natural killer lymphocyte subsets in patients with antiphospholipid syndrome.