The destabilization of factor VIII by a vitamin K dependent protein

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Abstract
Since a vitamin K-dependent protein, protein C, can inactivate factor VIII, a study was undertaken to determine if the level and stability of factor VIII in plasma are influenced by such a protein. Factor VIII lability was determined by incubating citrated plasma, diluted 1:10 and 1:20 in pH 7.2 imidizole buffer, for 6 h at 37.degree. C. Normal plasma had a mean factor VIII of 98 .+-. 61 U/100 ml. The amount of factor VIII remaining after 6 h of incubation was 68 .+-. 14% of the original factor VIII level. In warfarinized patients, factor VIII (218 .+-. 65 U/100 ml) and VWF:AGN [von Willebrands disease antigen] (331 .+-. 102 U/100 ml) were elevated (P < 0.001). Following incubation, their residual activity was 103 .+-. 20% of the original factor VIII level. In samples taken after warfarin was discontinued, normal factor VIII lability returned, while plasma levels of factor VIII and VWF:AGN remained elevated. Similarly, in the plasma of a vitamin K deficient patient, increased factor VIII stability was also evident; lability was restored following vitamin K replacement. Factor VIII stability is determined in part by a vitamin K dependent protein. In the clinical states in which this protein is functionally absent, factor VIII is elevated and more stable.