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Gerinnungsfaktor XIII

Pharmakodynamische und pharmakokinetische Eigenschaften

Factor XIII

Pharmacodynamic and pharmacokinetic characteristics

  • Klinische Pharmakologie
  • Published:
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Zusammenfassung

Faktor XIII (FXIII) spielt eine wichtige Rolle für den suffizienten Ablauf der Hämostase. In den vergangenen zehn Jahren ist den angeborenen Mangelzuständen, aber vor allem auch dem erworbenen FXIII-Defizit vermehrt Aufmerksamkeit in der klinischen Forschung geschenkt worden. FXIII ist ein vielseitig wirkendes Enzym, das am Ende der Gerinnungskaskade zu einer kovalenten Verknüpfung von Fibrinfibrillen führt und die Verankerung des Blutgerinnsels unter Einbeziehung von Thrombozyten am Endotheldefekt verstärkt, sodass ein mechanisch stabiles Gerinnsel entstehen kann.

Die Symptome von FXIII-Mangelzuständen sind vielfältig und können von den pathognomonischen Nabelschnurblutungen, über kleinere Hauteinblutungen bis hin zu schwersten, teilweise lebensbedrohlichen Blutungsereignissen reichen, sodass sowohl bei angeborenem als auch erworbenem FXIII-Defizit eine prophylaktische oder therapeutische Substitutionstherapie erforderlich sein kann.

Gereinigtes, aus menschlichem Plasma gewonnenes FXIII-Konzentrat steht seit 1993 in Deutschland und weiten Teilen Europas sowie den USA und Kanada zur Verfügung. Die Applikation erfolgt intravenös und steht sofort nach Verabreichung im Plasma zur Verfügung. Die Anwendung sollte sich am aktuellen FXIII-Aktivitätsniveau orientieren und kann repetitiv, auch im Hinblick auf die Halbwertszeit von durchschnittlich 7,9 Tagen, verabreicht werden.

Die Anwendung gilt grundsätzlich als sicher und effektiv, es wurde jedoch in einzelnen Fällen, wie auch für andere Gerinnungsfaktoren, das Auftreten von inhibitorischen Antikörpern beschrieben.

Dieser Artikel soll dem Leser nach Durchsicht der aktuell verfügbaren Literatur eine Übersicht über die Details der Pharmakokinetik und Pharmakodynamik von aus menschlichem Plasma gewonnenem FXIII-Konzentrat geben. Zum detaillierten klinischen Einsatz und der Anwendung von FXIII-Konzentrat sowie einer Substitutionstherapie mittels GFP (gefrorenes Frischplasma) wird daher auf aktuelle Leitlinien und bereits publizierte aussagekräftige Arbeiten verwiesen.

Abstract

Factor XIII (FXIII) plays an important role in the field of blood coagulation. In the last decade, both congenital and acquired deficiencies have been investigated in clinical studies. FXIII is a versatile enzyme that leads to a covalent cross-linking of fibrin fibrils at the end of the clotting cascade and supports platelet adhesion to the damaged sub-endothelium with the result of a mechanically stable clot.

Symptoms of FXIII deficiencies vary within a broad spectrum from superficial skin bleeding episodes to severe, sometimes life threatening hemorrhage, requiring prophylactic or therapeutic replacement therapy.

Since 1993 purified plasma-derived FXIII concentrate has been available in Germany, large parts of Europe and in the USA and Canada. The administration is conducted intravenously, and FXIII is immediately available in the plasma. The dosage should be determined by measuring actual plasma FXIII-activity. Repetitive application is possible, especially with regard to the mean half-time of 7.9 days.

Administration is considered to be safe and effective, but there are some case reports, as with other coagulation factors, describing the appearance of inhibitory antibodies.

This summary seeks to provide an insight into the principle pharmacokinetic and pharmacodynamic characteristics of plasma-derived FXIII concentrate, reviewing the current literature. For detailed use in clinical settings, the application of FXIII concentrate or substitution therapy with fresh frozen plasma, we therefore refer to current guidelines and significant studies that have been recently published.

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Authors and Affiliations

  1. Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Frankfurt am Main, Theodor Stern Kai 7, 60590, Frankfurt am Main, Deutschland

    E. H. Adam, K. Zacharowski & C. F. Weber

  2. Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum des Saarlandes und medizinische Fakultät der Universität des Saarlandes, Homburg, Deutschland

    S. Kreuer

  3. Universitätsklinikum Würzburg, Klinik und Poliklinik für Allgemein-, Viszeral-, Gefäß- und Kinderchirurgie, Zentrum Operative Medizin, Universitätsklinikum Würzburg, Würzburg, Deutschland

    R. Wildenauer

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  4. C. F. Weber
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Correspondence to E. H. Adam.

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Interessenkonflikt

E.H. Adam, S. Kreuer, und R. Wildenauer erhielten Honorare für wissenschaftliche Vorträge von der Firma CSL Behring. C.F. Weber erhielt Honorare für wissenschaftliche Vorträge von den Firmen CSL Behring und TEM International. K. Zacharowski gibt an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

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C.F. Weber und R. Wildenauer haben gleichwertig zum Beitrag beigetragen und teilen sich die Letztautorschaft.

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Adam, E.H., Kreuer, S., Zacharowski, K. et al. Gerinnungsfaktor XIII. Anaesthesist 66, 52–59 (2017). https://doi.org/10.1007/s00101-016-0249-1

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