Pathophysiology of Antiphospholipid Syndrome

Abstract

The antiphospholipid syndrome is characterized by antibodies directed against phospholipid-binding proteins and phospholipids attached to cell membrane receptors, mitochondria, oxidized lipoproteins, and activated complement components. When antibodies bind to these complex antigens, cells are activated and the coagulation and complement cascades are triggered, culminating in thrombotic events and pregnancy morbidity that further define the syndrome. The phospholipid-binding proteins most often involved are annexins II and V, β2-glycoprotein I, prothrombin, and cardiolipin. A distinguishing feature of the antiphospholipid syndrome is the “lupus anticoagulant”. This is not a single entity but rather a family of antibodies directed against complex antigens consisting of β2-glycoprotein I and/or prothrombin bound to an anionic phospholipid. Although these antibodies prolong in vitro clotting times by competing with clotting factors for phospholipid binding sites, they are not associated with clinical bleeding. Rather, they are thrombogenic because they augment thrombin production in vivo by concentrating prothrombin on phospholipid surfaces. Other antiphospholipid antibodies decrease the clot-inhibitory properties of the endothelium and enhance platelet adherence and aggregation. Some are atherogenic because they increase lipid peroxidation by reducing paraoxonase activity, and others impair fetal nutrition by diminishing placental antithrombotic and fibrinolytic activity. This plethora of destructive autoantibodies is currently managed with immunomodulatory agents, but new approaches to treatment might include vaccines against specific autoantigens, blocking the antibodies generated by exposure to cytoplasmic DNA, and selective targeting of aberrant B-cells to reduce or eliminate autoantibody production.

SARS-CoV-2 infection and SLE: endothelial dysfunction, atherosclerosis, and thrombosis

“…The antibacterial plasma protein ß 2 GPI increases phagocytosis of phospholipid-exposing microparticles and apoptotic cells, inhibits platelet adhesion and aggregation mediated by vWF, and prevents protein S inactivation by the C4b-binding protein. These antithrombotic functions of ß 2 GPI are affected by antiß 2 GPI antibodies [ 64 ]. Furthermore, ß 2 GPI antibody complexes bind to cellular receptors on endothelial cells, monocytes, neutrophils, and platelets, activating these cells and enhancing their thrombogenicity [ 64 ].…”

“…These antithrombotic functions of ß 2 GPI are affected by antiß 2 GPI antibodies [ 64 ]. Furthermore, ß 2 GPI antibody complexes bind to cellular receptors on endothelial cells, monocytes, neutrophils, and platelets, activating these cells and enhancing their thrombogenicity [ 64 ].…”

Postnatal Depression in Women Over the Age of 18 Years and the Role of Social Workers in Supporting Them

“…The aPL found interfering with the natural existing anticoagulant protein including C, and S protein. Moreover, aPL also interfere with the fibrinolytic system resulting in breakage of fibrin (Green, 2021).…”

Antiphospholipid Antibodies in Pregnancy: Maternal and Neonatal Implications

“…Among these are β2-glycoprotein I 4 5 (apoH: β2GPI), prothrombin 6 (coagulation factor II: PT), and several others. 7 This led to the emergence of anti-β2GPI autoantibodies (aβ2GPI Abs) 8 with secondary refinement following epitope analysis of the antigen: anti-β2GPI-domain 1 autoantibodies (aβ2GPI-D1 Abs) 9 and anti-phosphatidylserine/PT antibodies (APS/PT Abs). 10…”

“…Among these are β2glycoprotein I 4,5 (apoH: β2GPI), prothrombin 6 (coagulation factor II: PT), and several others. 7 This led to the emergence of anti-β2GPI autoantibodies (aβ2GPI Abs) 8 with secondary refinement following epitope analysis of the antigen: anti-β2GPI-domain 1 autoantibodies (aβ2GPI-D1 Abs) 9 and anti-phosphatidylserine/PT antibodies (APS/PT Abs). 10 Based on similarities with heparin-induced thrombocytopenia, the pathophysiology of the morbidities observed in patients with positive aPL Abs was expected to be an autoantibody-mediated key cell activation syndrome.…”