title: Impaired fibrinolysis in the antiphospholipid syndrome.
abstract: The antiphospholipid syndrome (APS) is characterized by venous and/or arterial thrombosis, or recurrent fetal loss, in the presence of antiphospholipid antibodies (APL). The pathogenesis of APS is multifaceted and involves numerous mechanisms including activation of endothelial cells, monocytes, and/or platelets; inhibition of natural anticoagulant pathways such as protein C, tissue factor inhibitor, and annexin A5; activation of the complement system; and impairment of the fibrinolytic system. Fibrinolysis--the process by which fibrin thrombi are remodeled and degraded--involves the conversion of plasminogen to plasmin by tissue plasminogen activator (tPA) or urokinase-type plasminogen activator, and is tightly regulated. Although the role of altered fibrinolysis in patients with APS is relatively understudied, several reports suggest that deficient fibrinolytic activity may contribute to the pathogenesis of disease in these patients. This article discusses the function of the fibrinolytic system and reviews studies that have reported alterations in fibrinolytic pathways that may contribute to thrombosis in patients with APL. Some of these mechanisms include elevations in plasminogen activator inhibitor-1 levels, inhibitory antibodies against tPA or other components of the fibrinolytic system, antibodies against annexin A2, and finally, antibodies to beta(2)-glycoprotein-I (beta(2)GPI) that block the ability of beta(2)GPI to stimulate tPA-mediated plasminogen activation.
authors.affiliation: Cleveland Clinic Lerner College of Medicine, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
authors.forename: Katie A
authors.initials: KA
authors.lastname: Krone
authors.forename: Kristi L
authors.initials: KL
authors.lastname: Allen
authors.forename: Keith R
authors.initials: KR
authors.lastname: McCrae
mesh_terms: D016736:Antiphospholipid Syndrome / Q000503:physiopathology*; D005342:Fibrinolysis / Q000502:physiology*; D006801:Humans; D053482:beta 2-Glycoprotein I / Q000502:physiology*
chemical_list: D053482:beta 2-Glycoprotein I