Spectrum of complement-mediated thrombotic microangiopathies: pathogenetic insights identifying novel treatment approaches

Details

Serval ID
serval:BIB_E8592A26C04A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Spectrum of complement-mediated thrombotic microangiopathies: pathogenetic insights identifying novel treatment approaches
Journal
Semin Thromb Hemost
Author(s)
Riedl M., Fakhouri F., Le Quintrec M., Noone D. G., Jungraithmayr T. C., Fremeaux-Bacchi V., Licht C.
ISSN
1098-9064 (Electronic)
ISSN-L
0094-6176
Publication state
Published
Issued date
06/2014
Volume
40
Number
4
Pages
444-64
Language
english
Notes
Riedl, Magdalena
Fakhouri, Fadi
Le Quintrec, Moglie
Noone, Damien G
Jungraithmayr, Therese C
Fremeaux-Bacchi, Veronique
Licht, Christoph
eng
Research Support, Non-U.S. Gov't
Review
Semin Thromb Hemost. 2014 Jun;40(4):444-64. doi: 10.1055/s-0034-1376153. Epub 2014 Jun 9.
Abstract
Thrombotic microangiopathy (TMA) is a rare but severe disorder characterized by endothelial cell activation and thrombus formation. It manifests with the triad of hemolytic anemia, thrombocytopenia, and organ failure. Prompt diagnosis and treatment initiation are crucial for long-term outcome. TMA often manifests subsequent to infectious events, of which (enterohemorrhagic) Escherichia coli is the most frequently reported. TMA also occurs on the background of genetic/autoimmune defects in the complement system (atypical hemolytic uremic syndrome [aHUS]) and underlying conditions, such as pregnancy, transplantation, drugs, other glomerulopathies, vasculitides, or metabolic defects. Complement activation or defects in its regulation have now been described in an increasing number of acquired diseases with TMA. Coinciding with this expanding spectrum of complement-mediated diseases, the question arises which patients might benefit from a complement-targeted therapy. Success of therapy depends on the individual contribution of complement activation in disease pathogenesis. The advent of eculizumab, a monoclonal antibody that blocks terminal complement activation, has markedly improved outcome and quality of life in patients with aHUS. This review discusses the contribution of complement and highlights its complex interaction with inflammation, coagulation, and the endothelium. Treatment experiences focusing on eculizumab therapy are discussed in detail across the emerging spectrum of complement-mediated thrombotic microangiopathies.
Keywords
Antibodies, Monoclonal, Humanized/therapeutic use, Antiphospholipid Syndrome, Atypical Hemolytic Uremic Syndrome/immunology, Autoimmune Diseases, Bone Marrow Transplantation, Complement Activation, Complement System Proteins/*immunology, Diacylglycerol Kinase/immunology, Enterohemorrhagic Escherichia coli, Escherichia coli Infections/complications, Female, Homeostasis, Humans, Inflammation, Kidney Transplantation, Male, Pregnancy, Pregnancy Complications, Quality of Life, Recurrence, Stem Cell Transplantation, Thrombotic Microangiopathies/*immunology/microbiology/*therapy, Treatment Outcome
Pubmed
Create date
01/03/2022 10:18
Last modification date
02/03/2022 6:36
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