title: The Role of Complement Inhibition in Thrombotic Angiopathies and Antiphospholipid Syndrome.
abstract: Antiphospholipid syndrome (APS) is characterized by thrombosis (arterial, venous, small vessel) and/or pregnancy morbidity occurring in patients with persistently positive antiphospholipid antibodies (aPL). Catastrophic APS is the most severe form of the disease, characterized by multiple organ thromboses occurring in a short period and commonly associated with thrombotic microangiopathy (TMA). Similar to patients with complement regulatory gene mutations developing TMA, increased complement activation on endothelial cells plays a role in hypercoagulability in aPL-positive patients. In mouse models of APS, activation of the complement is required and interaction of complement (C) 5a with its receptor C5aR leads to aPL-induced inflammation, placental insufficiency, and thrombosis. Anti-C5 antibody and C5aR antagonist peptides prevent aPL-mediated pregnancy loss and thrombosis in these experimental models. Clinical studies of anti-C5 monoclonal antibody in aPL-positive patients are limited to a small number of case reports. Ongoing and future clinical studies of complement inhibitors will help determine the role of complement inhibition in the management of aPL-positive patients.
authors.affiliation: Hospital for Special Surgery, Weill Cornell Medicine, New York, United States. Phone : +90 212 774 22 91 E-mail : erkand@hss.edu.
authors.forename: Doruk
authors.initials: D
authors.lastname: Erkan
authors.forename: Jane E
authors.initials: JE
authors.lastname: Salmon
mesh_terms: D000026:Abortion, Habitual / Q000209:etiology / Q000276:immunology; D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000276:immunology*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D016736:Antiphospholipid Syndrome / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D002986:Clinical Trials as Topic; D015936:Complement C5a / Q000037:antagonists & inhibitors / Q000276:immunology; D051056:Complement Inactivating Agents / Q000627:therapeutic use*; D003171:Complement Pathway, Classical / Q000187:drug effects / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D006457:Hemoglobinuria, Paroxysmal / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D008297:Male; D051379:Mice; D015337:Multicenter Studies as Topic; D064887:Observational Studies as Topic; D010927:Placental Insufficiency / Q000209:etiology / Q000276:immunology; D011247:Pregnancy; D044087:Receptor, Anaphylatoxin C5a / Q000502:physiology; D019851:Thrombophilia / Q000209:etiology / Q000276:immunology; D057049:Thrombotic Microangiopathies / Q000188:drug therapy / Q000276:immunology*
chemical_list: D017152:Antibodies, Antiphospholipid; D061067:Antibodies, Monoclonal, Humanized; D051056:Complement Inactivating Agents; D044087:Receptor, Anaphylatoxin C5a; D015936:Complement C5a; C481642:eculizumab