149 - The Role of Endothelial Cells in the Antiphospholipid Syndrome

Summary

The antiphospholipid antibody syndrome (APS) is an enigmatic autoimmune disorder in which vascular thrombosis and/or recurrent spontaneous pregnancy losses occur in patients who have positive blood tests for antibodies that recognize phospholipid-binding proteins, predominantly β₂- glycoprotein I (β2GPI). The clinical tests that are currently available to detect the presence of APS antibodies are surrogate assays that were empirically derived from the biologic false-positive syphilis test and from unusual coagulation assays. The latter, paradoxically, report the inhibition of phospholipid-dependent coagulation reactions (referred to as the lupus anticoagulant [LA] phenomenon [1]). The clinical manifestations of the syndrome include venous and arterial thrombosis and embolism, disseminated large and small vessel thrombosis with accompanying multiorgan ischemia and infarction, stroke, premature coronary artery disease, and recurrent spontaneous pregnancy losses. Although the mechanism(s) of the syndrome have not yet been definitively established, a growing body of evidence supports a role for vascular endothelium in the disease process.

Formal criteria – known as the Sapporo Investigational Criteria – have been developed to define the diagnosis of APS (2). These criteria have been updated recently as the Sydney Investigational Criteria (3). These include a clinical history of one or more episodes of vascular thrombosis (involving any site) or history for pregnancy morbidity, together with laboratory evidence for a positive LA test or a medium- or high-titer anticardiolipin (aCL)immunoglobulin (Ig)G and/or IgM antibody measured by a standard assay for β2GPI-dependent aCL antibodies. The laboratory abnormalities must be persistent – that is, present on two or more occasions, at least 6 weeks apart.