Differences in Reactivity to Vitamin K Administration of the Vitamin K-Dependent Procoagulant Factors, Protein C and S, and Osteocalcin

ABSTRACT

Vitamin K is a trace nutrient necessary not only for the synthesis of four plasma clotting factors but also the production of two important anticlotting factors, protein C and protein S, and the synthesis of two bone proteins. If protein C and protein S are produced more quickly and/or in higher quantities than four plasma coagulation factors after vitamin K administration, then the result is unfavorable for stopping of hemorrhage. We therefore studied the difference of time dependence of prothrombin procoagulant factors, protein C and S and bone Gla protein after the administration of vitamin K in normal and vitamin K-deficient neonates. Results of our study showed that, on the whole, coagulation factors increased markedly more than anticlotting factors after vitamin K administration. Furthermore, the increase in bone Gla protein was also higher compared with protein C activity, although the detailed mechanism of the difference in reactivity of prothrombin procoagulant factors, protein C and S and bone Gla protein to vitamin K administration is not clear.

KEYWORD

Vitamin K - prothrombin - factor VII - factor IX - factor X - protein C - protein S - osteocalcin (bone Gla protein)

REFERENCES

• 1 Dam H. The antihaemorrhagic vitamin of the chick. Occurrence and chemical nature.  Nature . 1935;  135 652-653
• 2 Stenflo J, Fernlund P, Egan W. Vitamin K dependent modifications of glutamic acid residues in prothrombin.  Proc Natl Acad Sci USA . 1974;  71 2730-2733
• 3 Hauschka P V, Lian J B, Gallop P M. Direct identification of the calcium-binding amino acid, γ-carboxyglutamate, in mineralized bone.  Proc Natl Acad Sci USA . 1975;  72 3925-3929
• 4 Price P A, Urist M R, Otawara Y. Matrix Gla-protein, a new γ-carboxyglutamic acid-containing protein which is associated with the organic matrix of bone.  Biochem Biophys Res Commun . 1983;  117 765-771
• 5 Stenflo J. A new vitamin K-dependent protein. Purification from bovine plasma and preliminary characterization.  J Biol Chem . 1976;  251 355-363
• 6 DiScipio R G, Hermodson M A, Yates S G. A comparison of human prothrombin, factor IX (Christmas factor), factor X (Stuart factor) and protein S.  Biochemistry . 1977;  16 698-706
• 7 Horn J R, Danziger L H, Davis R J. Warfarin-induced skin necrosis: Report of four cases.  Am J Hosp Pharm . 1981;  38 1763-1768
• 8 Rose V L, Kwaan H C, Williamson K. Protein C antigen deficiency and warfarin necrosis.  Am J Clin Pathol . 1986;  86 653-655
• 9 Hardisty R M, Macpherson J C. A one-stage factor VIII (antihemophilic globulin) assay and its use on venous and capillary plasma.  Thromb Diath Haemorrh . 1962;  7 215-229
• 10 Martinoli J L, Stocker K. Fast functional protein C assay using Protac, a novel protein C activator.  Thromb Res . 1986;  43 253-264
• 11 Wakabayashi K, Sakata Y, Aoki N. Conformation-specific monoclonal antibodies to the calcium-induced structure of protein C.  J Biol Chem . 1986;  261 11097-11105
• 12 Suzuki K, Nishioka J. Plasma protein S activity measured using Protac, a snake venom derivered activator of protein C.  Thromb Res . 1988;  49 241-251
• 13 Takahashi H, Tatewaki W, Wada K. Plasma protein S in disseminated intravascular coagulation, liver disease, collagen disease, diabetes mellitus, and under oral anticoagulant therapy.  Clin Chim Acta . 1989;  182 195-208
• 14 Meguro T, Yamada K. A simple and rapid test of PIVKA-II in plasma.  Thromb Res . 1982;  25 109-114
• 15 Delmas P D, Stenner D, Wahner H W. Increase in serum bone γ-carboxyglutamic acid protein with aging in women.  J Clin Invest . 1983;  71 1316-1321
• 16 Shearer M J. Vitamin K.  Lancet . 1995;  345 229-234
• 17 Dowd P, Ham S-W, Naganathan S. The mechanism of action of vitamin K.  Annu Rev Nutr . 1995;  15 419-440
• 18 Matsuzaka T, Tanaka H, Fukuda M. Relationship between vitamin K dependent coagulation factors and anticoagulants (protein C and protein S) in neonatal vitamin K deficiency.  Arch Dis Child . 1993;  68 297-302