Coagulation time of blood is increased when vitamin K is deficient because the vitamin is required for the synthesis of prothrombin (factor II). Plasma clotting factors VII (proconvertin), IX (Christmas factor) and X (Stuart-Prower factor) also depend on vitamin K for their synthesis. These four blood-clotting proteins are synthesized in the liver in inactive precursor forms and then converted to biologically active proteins by the action of vitamin K (Suttie and Jackson, 1977). In deficiency, administration of vitamin K brings about a prompt response in four to six hours. In the absence of the liver, this response does not occur.
Bleeding disorders result from an inability of a liver microsomal enzyme, currently called the vitamin K-dependent carboxylase (Esmon et al., 1975), to carry out the normal post-translational conversion of specific glutamyl residues in the vitamin K-dependent plasma proteins to gamma-carboxyglutamyl residues (Nelsestuen et al., 1974). The result of insufficient vitamin K to serve as a cofactor for this enzyme is, therefore, a decrease in the rate of thrombin generation.
The action of converting inactive precursor proteins to biologically active forms involves the carboxylation of glutamic acid residues in the inactive molecules. Carboxylation allows prothrombin and the other procoagulant proteins to participate in a specific protein-calcium phospholipid interaction that is a necessity for their biological role (Suttie and Jackson, 1977). Four other vitamin K-dependent proteins have been more recently identified in plasma (i.e., proteins C, S, Z and M). Protein C and protein S play an anticoagulant rather than a procoagulant role in normal hemostasis (Suttie and Olson, 1990). Protein C inhibits coagulation, and, stimulated by protein S, it promotes fibrinolysis. Also, a protein C-S complex can partially hydrolyze the activated factors V and VIII and thus inactivate them. Protein S also has the potential to be involved in the regulation of bone turnover (Binkley and Suttie, 1995). Function for proteins M and Z is presently unknown.
The blood clotting mechanism can apparently be stimulated by either an intrinsic system, in which all the factors are in the plasma, or an extrinsic system. In the extrinsic system of coagulation, injury to the skin or other tissue frees tissue thromboplastin that in the present of various factors and calcium changes prothrombin in the blood to thrombin. The enzyme thrombin facilitates the conversion of the soluble fibrinogen into insoluble fibrin. Fibrin polymerizes into strands and enmeshes the formed elements of the blood, especially the red blood cells, to form the blood clot (Griminger, 1984). The final active component in both the intrinsic and extrinsic systems appears to activate the Stuart factor, which in turn leads to activation of prothrombin. The various steps involved in blood clotting are presented in Figure 1. The action of vitamin K is required at four different sites in these reactions.
