The coagulant response in sepsis and inflammation

M. Levi

doi:10.1055/s-0037-1617143

Hämostaseologie, Table of Contents

Hamostaseologie 2010; 30(01): 10-16
DOI: 10.1055/s-0037-1617143

Review

Schattauer GmbH

The coagulant response in sepsis and inflammation

Die Gerinnungsreaktion bei Sepsis und Entzündung

Authors

M. Levi

Department of Medicine and Vascular Medicine, Academic Medical Center, University of Amsterdam, The Netherlands

Abstract

Summary

Critically ill patients often have systemic activation of both inflammation and coagulation. Increasing evidence points to an extensive cross-talk between these two systems, whereby inflammation not only leads to activation of coagulation, but coagulation also considerably affects inflammatory activity. The intricate relationship between inflammation and coagulation may have major consequences for the pathogenesis of microvascular failure and subsequent multiple organ failure, as a result of severe infection and the associated systemic inflammatory response. Molecular pathways that contribute to inflammation-induced activation of coagulation have been precisely identified. Activation of the coagulation system and ensuing thrombin generation is dependent on an inter-leukin-6-induced expression of tissue factor on activated mononuclear cells and endothelial cells and is insufficiently counteracted by tissue factor pathway inhibitor. Simultaneously, endothelial-bound anticoagulant mechanisms, in particular the protein C system and the antithrombin system, are shut-off by pro-inflammatory cytokines. Modulation of inflammatory activity by activation of coagulation also occurs by various mechanisms. Activated coagulation proteases, such as the tissue factor-factor VIIa complex, factor Xa and thrombin can bind to protease-activated receptors on various cells and the ensuing intracellular signaling leads to increased production of pro-inflammatory cytokines and chemo kines. Physiological anticoagulants can modulate inflammatory activity as well. Increasing knowledge on the various mechanisms underlying activation of inflammation and coagulation may lead to better (adjunctive) management strategies in critically ill patients.

Zusammenfassung

Bei intensivpflichtigen Patienten kommt es oft zu einer systemischen Aktivierung von Entzün-dung und Koagulation. Zunehmend finden sich Hinweise auf eine weitreichende Wechselwirkung zwischen beiden Systemen, wonach die Entzündung nicht nur zu einer Aktivierung der Koagulation führt, sondern die Koagulation auch erheblich die Entzündungsaktivität beeinflusst. Die komplexe Beziehung zwischen Entzündung und Koagulation könnte bedeutende Konsequenzen für die Pathogenese von mikrovaskulärer Störung und anschließendem Multiorganversagen haben, die als Folge einer schweren Infektion und der damit verbundenen systemischen Entzündungsantwort auftreten. Molekulare Signalwege, die zu einer entzündungsbedingten Aktivierung der Koagulation beitragen, wurden bereits exakt identifiziert. Die Aktivierung des Gerinnungs-systems und die daraus folgende Bildung von Thrombin hängt von einer durch Interleukin-6 induzierten Expression des Gewebefaktors auf aktivierten mononukleären und endothelialen Zellen ab. Der Gewebefaktorinhibitor wirkt diesem Mechanismus nur unzureichend entgegen. Gleichzeitig werden endothelial gebundene Antikoagulationsmechanismen, insbesondere das Protein-C-System und das Antithrombin-System, durch proinflammatorische Zytokine abgeschaltet. Für die Regulie-rung der Entzündungsaktivität durch Aktivie-rung der Koagulation sind ebenfalls verschiedene Mechanismen verantwortlich. Aktivierte Gerinnungsproteasen wie der GewebefaktorFaktor-VIIa-Komplex, Faktor Xa und Thrombin können an proteaseaktivierte Rezeptoren auf verschiedenen Zellen binden und die anschließende intrazelluläre Signalübertragung führt zu einer verstärkten Bildung proinflammatorischer Zytokine und Chemokine. Physiologische Antikoagulanzien können die Entzündungsaktivität ebenfalls regulieren. Ein besseres Verständnis für die verschiedenen Mechanismen, die der Aktivierung von Entzün-dung und Koagulation zugrunde liegen, könnte zur Entwicklung besserer (zusätzlicher) Behandlungsstrategien für intensivpflichtige Patienten führen.

Keywords

Coagulation - sepsis - inflammation

Schlüsselwörter

Koagulation - Sepsis - Entzündung

Full Text

References

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