Complement activation in thrombotic microangiopathy

D. Karpman; R. Tati

doi:10.5482/HAMO-12-12-0025

Hämostaseologie, Table of Contents

Hamostaseologie 2013; 33(02): 96-104
DOI: 10.5482/HAMO-12-12-0025

Review

Schattauer GmbH

Complement activation in thrombotic microangiopathy

Komplementaktivierung bei thrombotischer Mikroangiopathie

D. Karpman

¹Department of Paediatrics, Clinical Sciences Lund, Lund University, Sweden

,

R. Tati^*

¹Department of Paediatrics, Clinical Sciences Lund, Lund University, Sweden

› Author Affiliations

Abstract

Summary

The endothelium lining the vascular lumen is continuously exposed to complement from the circulation. When erroneously activated on host cells, complement may generate a deleterious effect on the vascular wall leading to endothelial injury, exposure of the subendothelial matrix and platelet activation.

In this review the contribution of complement activation to formation and maintenance of the pathological lesion termed thrombotic microangiopathy (TMA) is discussed. TMA is defined by vessel wall thickening affecting mainly arterioles and capillaries, detachment of the endothelial cell from the basement membrane and intraluminal thrombosis resulting in occlusion of the vessel lumen. The TMA lesion occurs in haemolytic uraemic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). HUS is further sub-classified as associated with Shiga toxin-producing Escherichia coli (STEC-HUS) or with complement dysregulation (atypical HUS) as well as other less common forms. The contribution of dysregulated complement activation to endothelial injury and platelet aggregation is reviewed as well as specific complement involvement in the development of HUS and TTP.

Zusammenfassung

Das Endothel, die zum Lumen ausgerichtete Gefäßinnenwand, ist im ständigen Kontakt mit zirkulierenden Komplementfaktoren. Wenn Komplement irrtümlich auf Wirtszellen aktiviert wird, kann es eine zerstörerische Wirkung auf die Gefäßwand auslösen, die zu Endothelschädigung, Exposition der sub- endothelialen Matrix und Thrombozytenaktivierung führt.

In dieser Übersicht wird der Beitrag diskutiert, den die Komplementaktivierung zur Entstehung und Aufrechterhaltung der pathologischen Läsion, der so genannten thrombotischen Mikroangiopathie (TMA), leistet. Die TMA ist definiert durch eine vorwiegend arterioläre und kapilläre Gefäßwandverdickung, Ablösung der Endothelzellen von der Basalmembran und Thrombosierung des Lumens, die zum Gefäßverschluss führt. Die TMA-Läsion tritt bei urämisch-hämolytischen Syndrom (HUS) und thrombotisch-thrombozytischer Purpura (TTP) auf. HUS wird unterteilt in mit Shiga-Toxin-produzierende Escherichia coli assoziierte HUS (STEC-HUS) und mit Komplementregulationsstörung assoziierte HUS (atypische HUS) sowie andere seltene Formen. Wir betrachten den Anteil, den eine Fehlregulation der Komplementaktivierung bei der Endothelschädigung und der Thrombozytenaggregation hat, sowie die spezifische Beteiligung des Komplements bei der Entstehung von HUS und TTP.

Keywords

Complement

Schlüsselwörter

Komplement

Full Text

References

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