Links between the immune and coagulation systems: How do Antiphospholipid antibodies cause thrombosis?

Inflammation and immune activation have been associated with thrombosis in a number of settings. We have been interested in the question of how the presence of a type of autoantibody, so-called antiphospholipid antibody, leads to thrombosis. Several mechanisms have been proposed including modulation of tissue factor expression, enhancement of procoagulant binding to platelets, and interference with antithrombotic mechanisms. We developed a cell-based model of coagulation that, unlike current coagulation assays, reflects some of the in vivo activities of antiphospholipid antibodies. Antiphospholipid antibodies against the phospholipid-binding protein beta-2-glycoprotein-1 enhance thrombin generation in this model system, primarily by enhancing procoagulant reactions on tissue factor-bearing cells.