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.
Waintraub
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Sussman
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D001779:Blood Coagulation Factors / Q000378:metabolism*; D000939:Epitopes / Q000032:analysis; D005169:Factor VIII / Q000502:physiology*; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D011486:Protein C; D012964:Sodium / Q000494:pharmacology; D014812:Vitamin K / Q000378:metabolism; D014859:Warfarin / Q000494:pharmacology; D014841:von Willebrand Factor / Q000378:metabolism
D001779:Blood Coagulation Factors; D000939:Epitopes; D006023:Glycoproteins; D011486:Protein C; D014841:von Willebrand Factor; D014812:Vitamin K; D014859:Warfarin; D005169:Factor VIII; D012964:Sodium