Antiphospholipid antibodies: proposed mechanisms of action.
Antiphospholipid antibodies (APA) are a family of immunoglobulins that react with anionic phospholipids, or anionic phospholipids-protein complexes. Recent evidence would support the latter definition. Lupus anticoagulants (LA) inhibit in vitro phospholipid dependent coagulation tests [e.g., activated partial thromboplastin time (APTT), prothrombin time (PT), and dilute Russell viper venom time (dRVVT)]. This inhibition appears to be specific for reagent phospholipids. The addition of freeze-thawed platelets or activated platelets will result in correction of the LA-induced abnormality. Anticardiolipin antibodies (ACA) are related to LA but appear to be distinct. ACA are detected by solid phase assays (ELISA, RIA) and require a plasma cofactor: beta 2 Glycoprotein-I (beta 2 GPI). ACA and LA activities can be separated in individual patient plasmas by affinity chromatography. In some instances they are of differing isotypes. Preliminary evaluation of beta 2 GPI in coagulation assays suggests it may function as a cofactor for LA activity. Recent work also suggests human prothrombin may represent a necessary cofactor for in vitro LA activity. Paradoxically, patients with LA/ACA may sustain thromboembolic events involving both venous and arterial sites. The prothrombotic properties of LA/ACA have not been satisfactorily characterized. A number of proposals have been reported, including inhibition of prostacyclin (PGI2) generation by endothelial cells, decreased activity of the protein C system, impaired fibrinolysis, and inhibition of beta 2GPI. Among these various hypotheses, down regulation of the protein C system appears most plausible. Also, LA/ACA may interfere with the phospholipase A2-phospholipid substrate complex involved in the generation of arachidonic acid from membrane phospholipids.
Triplett
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Indiana University School of Medicine, Department of Pathology, Muncie.
D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000032:analysis / Q000502:physiology*; D016736:Antiphospholipid Syndrome / Q000209:etiology* / Q000503:physiopathology; D000990:Antithrombin III / Q000378:metabolism; D001327:Autoimmune Diseases / Q000453:epidemiology* / Q000503:physiopathology; D001778:Blood Coagulation Disorders / Q000209:etiology; D001792:Blood Platelets; D004195:Disease Models, Animal; D004730:Endothelium, Vascular; D005260:Female; D006801:Humans; D051379:Mice; D011247:Pregnancy; D011248:Pregnancy Complications / Q000209:etiology / Q000503:physiopathology
D017152:Antibodies, Antiphospholipid; D000990:Antithrombin III