Gerinnungsstörungen bei Sepsis

Zusammenfassung

Klinische und experimentelle Untersuchungen belegen die wichtige Rolle von Endotoxin und von verschiedenen inflammatorischen Mediatoren, die über eine Aktivierung des extrinsischen Systems eine systemische Gerinnungsaktivierung vermitteln, welche der Entwicklung der Organdysfunktion vorausgeht. Das intrinsische System scheint diese Gerinnungsaktivierung über die Induktion des Schockzustands zu verstärken und so zur vermehrten intravasalen Ablagerung von Fibrin – und wichtiger noch – zur erhöhten Aktivierung des Gefäßendothels beizutragen. Die Aktivierung des Gefäßendothels verursacht eine Verstärkung der Leukozyten-/Endothelzell-Interaktion und damit letztendlich eine Verschlechterung der kapillaren Organperfusion mit der Entwicklung der Organdysfunktion. Die Therapie der Gerinnungsaktivierung bei Sepsis beinhaltet an erster Stelle die Fokussanierung durch chirurgische Therapie und Antibiotikatherapie. Adjuvant stehen verschiedene Strategien zur spezifischen Therapie der Gerinnungsstörung bei Sepsis zur Verfügung, die meist auf der Augmentierung des natürlichen inhibitorischen Potentials des Organismus beruhen. Hierbei ist insgesamt pleiotrop angreifenden Therapieansätzen (z. B. Antithrombin, Protein C) mit dokumentierter antiinflammatorischer bzw. die Mikrozirkulation verbessernder Wirkung der Vorzug gegenüber solchen Strategien zu geben, die nur punktuell angreifen (z. B. Hirudin). Obwohl dieses Therapiekonzept pathophysiologisch gut zu begründen ist und tierexperimentell abgesichert wurde, muß der positive Einfluß dieser adjuvanten Therapiemaßnahme auf die Letalität von Patienten mit Sepsis und septischem Schock in klinischen Studien erst noch weiter abgesichert werden.

Summary

Clinical and experimental studies showed the key role of endotoxin and consecutively released inflammatory mediators during sepsis. These mediators are known to activate coagulatory pathways mainly via stimulation of the extrinsic system of coagulation. Hereby the extrinsic system mediates systemic coagulatory activation and finally promotes the development of organ dysfunction. The intrinsic system of coagulation, however, is known to amplify coagulatory activation by the induction of vasodilation and shock, thereby generating increased intravascular deposition of fibrin with increased activation of the vascular endothelium. Endothelial activation increases leukocyte/endothelial cell interaction and finally decreases organ perfusion leading to the development of multiple organ dysfunction syndrome. Sepsis is to be treated primarily by the clearance of the septic focus (surgery, antibiotic therapy). Specific measures of adjunctive sepsis therapy include coagulation inhibitor substitution. This therapeutical strategy bases on the augmentation of the natural coagulatory inhibitor potential of the organism. Pleiotropically working substances with well-documented antiinflammatory effects (antithrombin, protein C) are to be preferred in comparison to substances that modulate the coagulation cascade only in one enzyme of the coagulation cascade (e.g. hirudin). Although the concept of coagulatory inhibitor therapy during sepsis seems reasonable in view of sepsis pathophysiology and experimental findings, this concept has to prove its beneficial effects during prospective clinical trials.

Schlüsselwörter

Sepsis - disseminierte intravasale Gerinnung - Gerinnungsinhibitoren

Keywords

Sepsis - disseminated intravascular coagulation - coagulation inhibitors

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