title: Antiphospholipid antibodies and the coagulation cascade.
abstract: Hemostasis is a highly controlled system of associated biophysical and biochemical events requiring a number of molecular and cellular interactions, among which molecular assembly at surfaces is an obligatory mechanism. The exposure of flowing blood to subendothelial components results in platelet adhesion, activation, and aggregation with simultaneous exposure of negatively charged phospholipids, which serves as a template for the formation of enzyme-cofactor-substrate complexes. The locally formed proteases activate surface-bound zymogens in a sequence culminating in the formation of thrombin. Fibrinogen is transformed into fibrin by thrombin, which may also activate protein C on phospholipid membranes when bound to TM. Activated protein C is a potent anticoagulant that inactivates coagulation-activated cofactors Va and VIIIa. During this process, proteins bound to the phospholipid surfaces may adopt new configurations and expose neoepitopes, which may elicit an immunologic response giving rise to the generation of antiphospholipid antibodies. These antibodies may then interfere with the procoagulant or anticoagulant activities of the target protein-phospholipid complexes. The apolipoprotein beta 2GPI and prothrombin are the most frequently found cofactors for antiphospholipid antibodies. Components of the protein C pathway have also been identified as cofactors. The pathophysiologic effects of antiphospholipid antibodies on the thrombotic accidents observed in patients with the antiphospholipid syndrome have not been established yet.
authors.affiliation: INSERM U.460, Remodelage Cardiovasculaire Faculté de Médecine Xavier-Bichat, Paris, France. angles@infobiogen.fr
authors.forename: E
authors.initials: E
authors.lastname: Anglés-Cano
authors.forename: M C
authors.initials: MC
authors.lastname: Guillin
mesh_terms: D017152:Antibodies, Antiphospholipid / Q000276:immunology* / Q000502:physiology; D016736:Antiphospholipid Syndrome / Q000276:immunology* / Q000503:physiopathology; D001777:Blood Coagulation / Q000276:immunology*; D002462:Cell Membrane / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D010743:Phospholipids; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000276:immunology / Q000494:pharmacology; D011486:Protein C / Q000494:pharmacology; D012307:Risk Factors; D013927:Thrombosis / Q000276:immunology* / Q000473:pathology
chemical_list: D017152:Antibodies, Antiphospholipid; D010743:Phospholipids; D019038:Platelet Glycoprotein GPIb-IX Complex; D011486:Protein C