Inherited resistance to activated protein C is
corrected by anticoagulant cofactor activity found to be a property of factor
V. |
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| Authors: | B Dahlb?ck B Hildebrand |
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| Affiliation: | Department of Clinical Chemistry, University of Lund, Malmö General Hospital, Sweden. |
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| Abstract: | Recently, our laboratory described a defect inanticoagulant response to activated protein C (APC). This response, APCresistance, was shown to be inherited and associated with familialthrombophilia. As other possible mechanisms were excluded, APC resistance washypothesized to be due to deficiency of a previously unrecognized cofactor ofAPC. The aim of the present study was to isolate and characterize this factor.Plasma from an individual with pronounced inherited APC resistance was used astest plasma in a biological assay which monitored APC cofactor activity duringits isolation from normal plasma. A purification procedure was devised thatyielded a protein which was shown to be identical to coagulation factor V. Itproved impossible to separate the APC cofactor activity from factor V, even byaffinity chromatography using a monoclonal antibody against factor V. Theaffinity-purified factor V corrected the poor anticoagulant response to APC ofAPC-resistant plasma in a dose-dependent manner. Because the APC-resistantplasma contained normal levels of factor V procoagulant activity, the resultsindicated APC resistance to be due to a selective defect in the anticoagulantfunction of factor V. The present results show factor V not only to expressprocoagulant properties after its activation by thrombin but also to play animportant part in the anticoagulant system as cofactor to APC. |
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