SearchPublisher and Institutes
You are here: Home :: Area NEM :: Medical science :: Human medicine
B. Dahlbäck
APC resistance: What have we learned since 1993? / APC-Resistenz: Was haben wir seit 1993 hinzugelernt?
APC resistance, defined as a poor anticoagulant response to activated protein C (APC), was described in February 1993 as a novel and important inherited risk factor of thrombosis. An avalanche of research activities was triggered that during the past eleven years has elucidated not only the molecular mechanisms of APC resistance, but also general pathogenetic mechanisms of thrombosis. In 1994, factor V (FV) was identified as the factor associated with APC resistance, and a point mutation in the FV gene (Arg506Gln or FV Leiden) was found to be the genetic cause of APC resistance. This mutation eliminates one of three APC-cleavage sites in FV, which not only results in impaired APCmediated degradation of FVa, but surprisingly also of FVIIIa. The dual effects of FV Leiden were explained by the discovery of a novel property of FV, namely that FV has the potential to express anticoagulant activity in addition to being a procoagulant protein. As an anticoagulant, FV functions as an APC cofactor in synergy with protein S in the regulation of FVIIIa in the tenase complex. Studies of APC resistance and FV Leiden performed in many laboratories world-wide have given insights into clinical, epidemiological as well as molecular details. This review focuses on what we have learned since 1993 about the molecular mechanisms of APC resistance and the involvement of FV in the regulation of blood coagulation by the anticoagulant protein C system.
LaboratoriumsMedizin, Walter de Gruyter
Print ISSN: 0025-8466
Volume: 28, 02/2004
Pages: 21 - 27