title: Antiphospholipid-mediated thrombosis: interplay between anticardiolipin antibodies and vascular cells.
abstract: The antiphospholipid syndrome (APS) is characterized by thrombosis or pregnancy morbidity in the presence of antiphospholipid autoantibodies (aPL). aPL are a heterogeneous family of autoantibodies with diverse cross-reactivities whose origin and role have not been fully elucidated. Many of the autoantibodies associated with APS are directed against phospholipid-binding plasma proteins, such as beta2-GPI and prothrombin, or phospholipid-protein complexes. The mechanisms by which aPL cause thrombosis are not completely understood. There is no unique mechanism able to explain all symptoms associated with the presence of aPL. Different theories have been proposed, including the effect of aPL on endothelial cells, monocytes, and platelets. aPL are able to recognize, injure, or activate cultured vascular endothelial cells. Cultured endothelial cells incubated with aPL express increased levels of cell adhesion molecules and tissue factor (TF), an effect mediated by beta2-GPI, and may promote inflammation and thrombosis. Overexpression of TF has been also shown in monocytes in vitro and ex vivo. TF is the major initiator of coagulation in vivo; thus, its dysregulation may be one of the most important contributors to thrombosis. Effects of aPL upon platelets are not completely elucidated. aPL bind anionic phospholipid but they are normally in the inner side of cell membranes. When platelets are activated by different agonists, anionic phospholipids are exposed. There is some evidence showing that activated platelets are present in aPL-positive patients. Increased levels of beta-thrombomodulin, and microvesicle formation seem to support this hypothesis. Activated platelets may contribute to thrombosis by persistent exposure of a procoagulant surface.
authors.affiliation: Research Unit and Hematology Department, Reina Sofía University Hospital, Cordoba, Spain. rosario.lopez.exts@juntadeandalucia.es
authors.forename: Chary
authors.initials: C
authors.lastname: López-Pedrera
authors.forename: Paula
authors.initials: P
authors.lastname: Buendía
authors.forename: Nuria
authors.initials: N
authors.lastname: Barbarroja
authors.forename: Emilio
authors.initials: E
authors.lastname: Siendones
authors.forename: Francisco
authors.initials: F
authors.lastname: Velasco
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Cuadrado
mesh_terms: D017153:Antibodies, Anticardiolipin; D017152:Antibodies, Antiphospholipid; D001792:Blood Platelets / Q000473:pathology; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D006801:Humans; D009000:Monocytes / Q000473:pathology; D011247:Pregnancy; D013927:Thrombosis / Q000209:etiology* / Q000473:pathology
chemical_list: D017153:Antibodies, Anticardiolipin; D017152:Antibodies, Antiphospholipid