The Pathogenesis of the Antiphospholipid Syndrome

Renal involvement in antiphospholipid syndrome

“…Secondly, aPL might interact with specific cell-surface receptors (proteins, lipids or both) and induce signals downstream that will ultimately result in upregulation of cell-surface proteins. 10 We and others have suggested that expression of tissue factor, the major coagulation initiator in vivo, by endothelial cells and monocytes is a leading mechanism contributing to thrombosis in APS.11 Several other processes have been related to aPLinduced thrombosis, such as conformational and post-translational redox modifications of B2GPI, decreased activity of endothelial nitric oxide synthase and complement activation. aPL can also cause direct or indirect cellular effects on endothelial cells, monocytes and platelets, mainly through binding to B2GPI expressed on cell membranes.10 Additionally, interaction of aPL with proteins implicated in clotting regulation-such as prothrombin, factor X, protein C and plasmin-might interfere with the inactivation of pro-coagulant factors and fibrinolysis.…”

“…Rather, the theory that aPL creates a prothrombotic state that increases the risk of thrombotic events in the presence of another prothrombotic factor has been purported.9 The aPL-related prothrombotic state could be induced by many different pathophysiological mechanisms, such as cellular effects (on platelet membranes, endothelial cells and monocytes), increases in expression of plasma coagulation regulatory proteins (clotting components, such as antithrombin, protein C and protein S) and fibrinolysis. 10 The proposed pathophysiological mechanisms can be categorized into two types. Firstly, aPL might act in vivo by disrupting pro-coagulant and anticoagulant reactions occurring on cell membranes.…”

The Laboratory Diagnosis of the Antiphospholipid Syndrome

“…These autoantibodies (lupus anticoagulant or LAC) have the ability to prolong clotting times in vitro and the commonly called antiphospholipid antibodies (aPL) [6]. Other antigenic targets include procoagulant proteins (high molecular weight kininogen, FV, FVII); anticoagulant proteins (protein C and S); annexin A2 and A5; plasmin and vimentin [2].…”

“…The activation of platelets, endothelium, monocytes, coagulation proteins and inflammatory cascade together with inhibition of fibrinolytic pathway and natural anticoagulation pathways (e.g. : protein C) leads to thrombosis [6]. Though, according to the widely accepted pathogenic model, it is believed that the autoantibodies directed against phospholipids are not pathogenic [9], current research reveals evidence for the pathogenic role of cofactor independent aPL and that the clinical studies do not support a dominant pathogenic role for antib 2 GPI antibodies [10].…”

The spectrum between antiphospholipid syndrome and systemic lupus erythematosus

“…However, in the last decades, the presence of antinuclear antibodies, hypocomplementemia, non-thrombotic kidney disease, and renal failure were all documented in patients diagnosed with primary APS and the activation of complement was found to be related with APS in experimental models [2]. Last but not the least, the antiphospholipid antibodies serve as criteria for both syndromes and are present in 100 % of APS patients and in up to 40 % of SLE patients, of which many will eventually develop overt APS [2][3][4]. Hence, the great heterogeneity and overlap between these autoimmune diseases raised the debate: Are they a single condition with varied phenotypes, or different diseases with diverse pathogenic mechanisms sharing phenotypes?…”