Mechanisms of antiphospholipid-induced thrombosis: Effects on the protein C system

An acquired resistance to activated protein C (APC) has been demonstrated in patients with antiphospholipid antibodies (aPL). Recent studies report interactions between β2 glycoprotein I (β2GPI) and prothrombin-binding antibodies and the protein C system. Some aPL in patients recognize one or more conformational epitopes shared by β2GPI and catalytic domains of APC. Both β2GPI and antiprothrombin antibodies are associated with APC resistance. Several clinical studies have focused on an association between aPL and APC resistance, determined by classic activated partial thromboplastin time-based tests. It has been shown in most studies that APC resistance was associated with lupus anticoagulants. APC resistance is also associated with thrombosis, especially venous thromboembolism. Several recent studies have reported a novel integrated approach of coagulation using calibrated automated thrombography. This technique allows an approach of APC sensitivity without interference with lupus anticoagulants. Clinical associations between APC resistance and thromboembolic events have been demonstrated.