Antiphospholipid antibodies and the coagulation cascade

The coagulation cascade consists of a series of surface reactions where coa gulation factors and cofactors assemble on a negatively charged phospholipi d surface. In this process, locally formed proteases activate surface-bound substrates and culminate in the formation of thrombin that transforms fibr inogen into a polymerized fibrin network. Activation of protein C, a potent anticoagulant, requires also phospholipid surfaces. It is possible that an tibodies may originate from an immunological response to neoepitopes genera ted by the formation of these short-lived protein-phospholipid complexes. T hese antibodies then may recognize some of the phospholipid-bound proteins and interfere thereby with their procoagulant or anticoagulant activities. beta (2)-glycoprotein I, prothrombin and components of the protein C pathwa y are some of the most frequent protein cofactors of these antibodies. Anti genic heterogeneity and single antibody targeting cannot explain the pathop hysiology of associated thrombotic accidents.