Antiphospholipid antibodies and the protein C pathway

Among the mechanisms suggested for the prothrombotic activity of lupus anti coagulant and antiphospholipid antibodies is the direct inhibition of the a nticoagulant activated protein C (APC) pathway. Although some pathological antibodies may be directed towards the proteins involved, we hypothesize th at populations exist which selectively inhibit the APC complex as a result of differences in the phospholipid requirements of this complex as compared to those of the procoagulant complexes. The most prominent feature is the requirement for the presence of phosphatidylethanolamine in the membrane fo r APC anticoagulant function. This mimics the requirements for inhibitory a ctivity of at least a subset of autoantibodies associated with thrombosis. The role of oxidation of the phospholipid in APC function and antibody reac tivity is also discussed. (C) 2000 Academic Press.