Complement and the prothrombotic state.
Blood
; 139(13): 1954-1972, 2022 03 31.
Article
em En
| MEDLINE
| ID: mdl-34415298
ABSTRACT
In 2007 and 2009, the regulatory approval of the first-in-class complement inhibitor eculizumab revolutionized the clinical management of 2 rare, life-threatening clinical conditions paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS). Although being completely distinct diseases affecting blood cells and the glomerulus, PNH and aHUS remarkably share several features in their etiology and clinical presentation. An imbalance between complement activation and regulation at host surfaces underlies both diseases precipitating in severe thrombotic events that are largely resistant to anticoagulant and/or antiplatelet therapies. Inhibition of the common terminal complement pathway by eculizumab prevents the frequently occurring thrombotic events responsible for the high mortality and morbidity observed in patients not treated with anticomplement therapy. Although many in vitro and ex vivo studies elaborate numerous different molecular interactions between complement activation products and hemostasis, this review focuses on the clinical evidence that links these 2 fields in humans. Several noninfectious conditions with known complement involvement are scrutinized for common patterns concerning a prothrombotic statues and the occurrence of certain complement activation levels. Next to PNH and aHUS, germline-encoded CD59 or CD55 deficiency (the latter causing the disease complement hyperactivation, angiopathic thrombosis, and protein-losing enteropathy), autoimmune hemolytic anemia, (catastrophic) antiphospholipid syndrome, and C3 glomerulopathy are considered. Parallels and distinct features among these conditions are discussed against the background of thrombosis, complement activation, and potential complement diagnostic and therapeutic avenues.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Síndrome Hemolítico-Urêmica Atípica
/
Hemoglobinúria Paroxística
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article