Effect of heparanase inhibitor on tissue factor overexpression in platelets and endothelial cells induced by anti-β2-GPI antibodies. Reply to comment from Mackman et al

Anti‐phospholipid syndrome (APS) is characterized by arterial and/or venous thrombosis and pregnancy morbidity associated with the presence of “anti‐phospholipid antibodies.” Thrombosis may be the result of a hypercoagulable state related to activation of endothelial cells and platelets by anti‐β2‐glycoprotein I (β2‐GPI) antibodies. Anti‐β2‐GPI antibodies induce a proinflammatory and procoagulant phenotype in these cells that, after activation, express tissue factor (TF), the major initiator of the clotting cascade, playing a role in thrombotic manifestations. Moreover, TF expression may also be induced by heparanase, an endo‐β‐D‐glucuronidase, that generates heparan sulfate fragments, regulating inflammatory responses