Effect of coumadin-induced coagulopoietin plasma on vitamin K-dependent carboxylation of liver microsomes.

Coumadin-treated rabbits have a humoral substance(s) (coagulopoietin) which is capable of elevating vitamin K-dependent coagulation factors when injected into recipient rabbits (Karpatkin & Karpatkin, 1973). Biologic levels of coagulation factors II, V, VII and X; immunologic levels of factors II and X; and vitamin K-dependent liver microsomal carboxylase activity were measured in recipient rabbits receiving coumadin-induced coagulopoietin plasma. Factor II biologic activity increased 3.5-fold compared to the increase in immunologic activity. Factor X biologic activity increased 1.7-fold compared to the increase in immunologic activity. This indicates an increase in specific activity of factors II and X. Coumadin-induced coagulopoietin plasma had no effect on vitamin K-dependent liver microsomal carboxylase activity in vitro. However, livers obtained from recipient animals treated with coumadin-induced coagulopoietin plasma enhanced their carboxylase activity (compared to control animals) 2.4-fold employing endogenous microsomal precursor for carboxylation, and 6.2-fold employing synthetic substrate, phe-leu-glu-glu-val. Thus, coumadin-induced coagulopoietin plasma enhances the biologic activity of vitamin K-dependent coagulation factors II, VII, and X as well as the ex vivo vitamin K-dependent carboxylase activity of liver microsomes.