The influence of anti‐endothelial/antiphospholipid antibodies on fibrin formation and lysis on endothelial cells

Summary The prothrombotic mechanisms associated with antiphospholipid antibodies remain incompletely defined. Antibody binding to endothelial cells in vitro is a feature of antiphospholipid antibody‐positive sera. We hypothesised that impairment of endothelium‐dependent fibrinolysis by antiphospholipid/anti‐endothelial antibodies is a contributory factor in the pathogenesis of thrombosis. We also aimed to confirm the displacement of annexin‐V from endothelial cells and enhanced fibrin formation. Binding of immunoglobulin (Ig) from antiphospholipid antibody‐positive sera to endothelial cells was examined using a cell‐based enzyme‐linked immunosorbent assay. Effects on fibrin formation and lysis were examined on cultured endothelial cell monolayers. Plasminogen activator inhibitor‐1 (PAI‐1) was assayed in supernatants. We confirmed antibody binding to endothelial cells. With four of 14 antiphospholipid antibody‐positive sera there was some prolongation of fibrin clot lysis time, consistent with impairment of endothelial fibrinolytic activity. Secretion of PAI‐1 was significantly correlated with clot lysis time on endothelial cell monolayers incubated with antiphospholipid/anti‐endothelial antibody‐positive sera, but not with control sera. IgG from antiphospholipid antibody‐positive sera had little effect on endothelial cell surface annexin‐V expression. We conclude that impaired endothelial fibrinolysis is a potential prothrombotic mechanism in subjects with antiphospholipid antibodies. We were unable to confirm enhanced displacement of annexin‐V from endothelium by antiphospholipid antibodies.