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Klinische Ergebnisse der Protein-C- und rhAPC-Substitution

  • C.-E. Dempfle
Conference paper

Zusammenfassung

Klinische Manifestation eines schweren Protein-C-Mangels ist die Purpura fulminans. Bei angeborenem Protein-C-Mangel tritt diese in der Neonatalperiode auf, bei weniger ausgeprägtem Protein-C-Mangel eventuell bei Einleitung einer Kumarintherapie in Form einer Kumarinnekrose. Erworbene Protein-C-Mangelzustände oder Beeinträchtigungen des Protein-C-Systems können ebenfalls mit einer Purpura fulminans einhergehen. Diese wird insbesondere bei Meningokokkensepsis, aber auch bei anderen Infektionserkrankungen beobachtet. Entwickelt sich eine Purpura fulminans nach Abklingen des akuten Infektes, finden sich häufig Autoantikörper gegen Komponenten des Protein-C-Systems. Niedrige Protein-C-Spiegel werden auch bei Patienten mit septischen Zustandsbildern ohne Purpura fulminans gemessen und besitzen einen prädiktiven Wert hinsichtlich des klinischen Resultates. Für die Therapie stehen Protein-C-Konzentrat aus Humanplasma sowie rekombinantes aktiviertes Protein C zur Verfügung. Indikation zur Substitution von Protein C ist der manifeste Protein-C-Mangel mit Purpura fulminans oder anderen thrombotischen Manifestationen, oder auch Kumarinnekrose, bei ungestörter endogener Protein-C-Aktivierung. Weitere Indikation ist die Prophylaxe thrombotischer Ereignisse bei angeborenem schwerem Protein-C-Mangel. Bei Patienten mit septischen Zustandsbildern kann die Aktivierung von Protein C durch MikroZirkulationsstörungen, Ablösung von Thrombomodulin vom Endothel sowie durch mikrovaskuläre Thrombosen beeinträchtigt sein. Hier erscheint die Gabe von ex vivo aktiviertem Protein C sinnvoll. In einer multizentrischen, plazebokontrollierten Doppelblindstudie zeigte sich eine deutliche Senkung der 28-Tage-Mortalität bei Patienten mit schwerer Sepsis durch Therapie mit rekombinantem aktiviertem Protein C.

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© Springer-Verlag Berlin Heidelberg 2002

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  • C.-E. Dempfle

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