Spectrum of Complement-Mediated Thrombotic Microangiopathies: Pathogenetic Insights Identifying Novel Treatment Approaches

Magdalena Riedl; Fadi Fakhouri; Moglie Le Quintrec; Damien G. Noone; Therese C. Jungraithmayr; Veronique Fremeaux-Bacchi; Christoph Licht

doi:10.1055/s-0034-1376153

Seminars in Thrombosis and Hemostasis, Inhaltsverzeichnis

Semin Thromb Hemost 2014; 40(04): 444-464
DOI: 10.1055/s-0034-1376153

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Spectrum of Complement-Mediated Thrombotic Microangiopathies: Pathogenetic Insights Identifying Novel Treatment Approaches

Autor*innen

Magdalena Riedl

¹Department of Pediatrics, Innsbruck Medical University, Innsbruck, Austria

²Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada

³Research Institute, Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada
Fadi Fakhouri

⁴Department of Nephrology and Immunology, ITUN and INSERM UMR S-1064, CHU de Nantes, Nantes, France
Moglie Le Quintrec

⁵Service de Nephrologie et de Transplantation Rénale, Hôpital Foch, Suresnes, France

⁶INSERM U1138, Cordelier Research Center “Complement and Diseases” Paris, France
Damien G. Noone

²Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada

³Research Institute, Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada
Therese C. Jungraithmayr

¹Department of Pediatrics, Innsbruck Medical University, Innsbruck, Austria
Veronique Fremeaux-Bacchi

⁶INSERM U1138, Cordelier Research Center “Complement and Diseases” Paris, France

⁷Department of Immunology, Assistance Publique-Hôpitaux de Paris Hôpital Européen Georges Pompidou, Paris, France
Christoph Licht

²Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada

³Research Institute, Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada

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

thrombotic microangiopathy - hemolytic uremic syndrome - thrombotic thrombocytopenic purpura - complement - eculizumab - plasma therapy

Volltext

Referenzen

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