Variations in warfarin concentration in blood and coagulant factors after artificial valve replacement

A proper dosage of warfarin after artificial cardiac valve replacements has been determined as an indication of coagulation activity. In some cases, the coagulation activity cannot be maintained within the therapeutic range because Prothrombin time (PT) values deviated from Thrombotest (TT) values. Here we studied each relationship between warfarin concentrations in blood, coagulation activity, vitamin Ks and other coagulation-related agents which were measured in patients administered warfarin after artificial cardiac valve replacements and whose coagulation activity was maintained within a therapeutic range, and in patients whose PT values deviated from TT values. The obtained results were interpreted as follows. 1) There was a high correlation between values from Thromborel S (a clot method) and values from Chromoquick (a method using a synthesized substrate). Since TT values had little variations compared to PT values, the former was an excellent indication of coagulation activity. 2) There was no correlation between warfarin concentrations in blood and coagulation activity in the group in which warfarin concentrations in blood vary within a day (Group B); but there was highly reverse correlation in the group in which warfarin concentrations in blood vary with days (Group A). 3) There was good correlation between warfarin concentrations and PIVKA-II concentrations in blood in Group A. Further, the concentration of Gla-Protein C was one microgram/ml or less on the fourth day from the initiation of warfarin administration. 4) For example, a patient whose PT value of 67% deviated from TT value of 19% on the eleventh day from the initiation of warfarin administration had vitamin K1-epoxide concentration of 2.68 ng/ml and MK-7 concentration of 1.26 ng/ml on the same day, respectively, which were higher levels than those in Group A.