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Proc Natl Acad Sci U S A. 1994 February 15; 91(4): 1396–1400. | PMCID: PMC43165 |
Inherited resistance to activated protein C is
corrected by anticoagulant cofactor activity found to be a property of factor
V. B Dahlbäck and B Hildebrand Department of Clinical Chemistry, University of Lund, Malmö General Hospital, Sweden. Abstract Recently, our laboratory described a defect in
anticoagulant response to activated protein C (APC). This response, APC
resistance, was shown to be inherited and associated with familial
thrombophilia. As other possible mechanisms were excluded, APC resistance was
hypothesized to be due to deficiency of a previously unrecognized cofactor of
APC. The aim of the present study was to isolate and characterize this factor.
Plasma from an individual with pronounced inherited APC resistance was used as
test plasma in a biological assay which monitored APC cofactor activity during
its isolation from normal plasma. A purification procedure was devised that
yielded a protein which was shown to be identical to coagulation factor V. It
proved impossible to separate the APC cofactor activity from factor V, even by
affinity chromatography using a monoclonal antibody against factor V. The
affinity-purified factor V corrected the poor anticoagulant response to APC of
APC-resistant plasma in a dose-dependent manner. Because the APC-resistant
plasma contained normal levels of factor V procoagulant activity, the results
indicated APC resistance to be due to a selective defect in the anticoagulant
function of factor V. The present results show factor V not only to express
procoagulant properties after its activation by thrombin but also to play an
important part in the anticoagulant system as cofactor to APC. Full text Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.0M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References. Images in this article Click on the image to see a larger version. These references are in PubMed. This may not be the complete list of references from this article. - Furie B, Furie BC. The molecular basis of blood coagulation. Cell. 1988 May 20;53(4):505–518. [PubMed]
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