The destabilization of factor VIII by a vitamin K dependent protein

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 X 2 imidizole buffer, for 6 h at 37 degrees 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 (331 +/- 102 U/100 ml) were elevated (P less than 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. We conclude that factor VIII stability is determined in part by a vitamin K dependent protein. In clinical states in which this protein is functionally absent, factor VIII is elevated and more stable.