Early days of APC resistance and FV Leiden

B. Dahlbäck

doi:10.1055/s-0037-1617167

Hämostaseologie, Inhaltsverzeichnis

Hamostaseologie 2008; 28(03): 103-109
DOI: 10.1055/s-0037-1617167

Original Article

Schattauer GmbH

Early days of APC resistance and FV Leiden

Erste Erkenntnisse zu APC-Resistenz und Faktor-V-Leiden

B. Dahlbäck

¹Department of Laboratory Medicine, Section of Clinical Chemistry, Lund University, The Wallenberg laboratory, University Hospital Malmö, Sweden

› Institutsangaben

Abstract

Summary

Venous thrombosis is a major medical problem annually affecting millions of individuals worldwide. It is a typical multifactorial disease, the pathogenesis involving both environmental and genetic risk factors. A single point mutation in the gene of coagulation factor V (FV), which results in the replacement of Arg506 with a Gln (FV Leiden) is the most common genetic risk factor known to date. The anti - coagulant activated protein C (APC) regulates the activity of FVa by cleaving several sites in FVa, and the Arg506 is one of them. APC resistance, which is the consequence of the FV Arg506Gln mutation, results a lifelong hypercoagulable state that increases the risk of thrombosis. APC resistance was discovered in my laboratory and the first paper was published in 1993. This was the starting point for an avalanche of research in many laboratories and several thousands of articles have been published since on this topic. The medical community amazingly quickly accepted the concept of APC resistance/FV Leiden as a major risk factor for thrombosis and millions of individuals are today tested for this condition. This review is a personal historical annotation about the early days of APC resistance.

Zusammenfassung

Die Venenthrombose ist ein bedeutendes medizinisches Problem. Jährlich sind weltweit Millionen Menschen davon betroffen. An der Pathogenese der multifaktoriellen Erkrankung sind sowohl erworbene als auch genetische Risikofaktoren beteiligt. Eine Punktmutation im Faktor-V-Gen, die zum Austausch von Arg506 durch ein Gln (Faktor-V-Leiden) führt, ist der häufigste bekannte genetische Risikofaktor. Das Antikoagulanz aktiviertes Protein C (APC) reguliert die Aktivität von Faktor Va durch Spaltung an mehreren Stellen u. a. an Arg506. Die APC-Resistenz, die eine Folge der Faktor-V-Arg506Gln-Mutation ist, führt lebenslang zu erhöhter Gerinnbarkeit, was auch das Thromboserisiko steigert. Die APC-Resistenz wurde in meinem Labor entdeckt, die erste Arbeit wurde 1993 publiziert. Es war der Ausgangspunkt für eine Flut wissenschaftlicher Untersuchungen in zahlreichen Labors. Inzwischen sind mehrere Tausend Artikel zu diesem Thema publiziert. Die Ärzteschaft erkannte das Konzept der APC-Resistenz/FV Leiden als wichtigen Risikofaktor für Thrombose erstaunlich schnell an. Millionen Menschen werden untersucht. Dieser Überblick ist eine persönliche historische Abhandlung zu den Anfangs - tagen der APC-Resistenz.

Keywords

Protein C - factor V - factor V Leiden - FV Leiden - thrombophilia - thrombosis - APC resistance

Schlüsselwörter

Protein C - Faktor V - Faktor-V-Leiden - FV-Leiden - Thrombophilie - Thrombose - APC-Resistenz

Volltext

Referenzen

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