Effect of warfarin on plasma concentrations of vitamin K dependent coagulation factors in patients with stable control and monitored compliance

Abstract

There is a discrepancy in the results of reported studies of levels of vitamin K dependent coagulation factors in patients on warfarin therapy. This may have arisen partly because of the problem of assuring compliance with therapy in outpatients. The plasma concentrations of the vitamin K dependent clotting factors II, VII, IX and X were studied in 23 outpatients whose adherence to prescribed warfarin therapy was determined using a pharmacological indicator of compliance. In these patients, who were shown to have consistently good compliance and stable anticoagulant control over a period of 3-6 months, the activities in plasma of the four coagulation factors were not equally suppressed. Factor IX levels were significantly greater than those of factor VII (P less than 0.0001) which in turn were significantly greater than the levels of factor II (P less than 0.0001) or factor X (P less than 0.0001). There was no significant difference between the levels of factors II and X which were depressed to a similar extent. The proportion of variability of the International Normalized Ratio (INR) explained by linear regression was 51-77% and a model was derived to predict the INR from the mean of the levels of the four clotting factors. The concentrations of the coagulation factors II, VII, IX and X are likely to be highly dependent on the degree of compliance with warfarin therapy which should be taken into account when investigating the behaviour of these factors.

Poor correlation of supratherapeutic international normalised ratio and vitamin K‐dependent procoagulant factor levels during warfarin therapy

“…Similar findings were also reported in 50 patients (Lind et al, 1997). In another study of 23 patients on long-term therapy, the levels of FII and FX were depressed to a significantly lower level than those of FVII and FIX (Kumar et al, 1990). The evidence from several studies suggests that the depletion of FII, and to a lesser extent FX, is crucial for the success of clinically effective oral anticoagulation, as well as its bleeding complications.…”

“…A decrease in vitamin K-dependent factor levels in patients on long-term coumadin therapy has been found to be quite variable in several studies (Paul et al, 1987;Kumar et al, 1990;Lind et al, 1997). In a study of 37 patients, Paul et al (1987) found that FX levels were the lowest, FII levels intermediate and FVII and FIX levels the highest.…”

Missense mutations at ALA‐10 in the factor IX propeptide: an insignificant variant in normal life but a decisive cause of bleeding during oral anticoagulant therapy

“…Coagulation studies revealed an disproportionate prolongation of the admissions APTTs, which was found to be caused by a strong and excessive decrease of FIX:C to 1-3% (Table I, plasma sample 1). Usually, during oral anticoagulant therapy FIX:C is decreased to a similar degree or remains even higher than the activity of the other vitamin K dependent factors (Kumar et al, 1990;Weiss et al, 1987). Therefore our patients were believed to have mild haemophilia B, which was exacerbated due to phenprocoumon administration.…”

“…Both coumarins function as vitamin K antagonists, decreasing the activities of the vitamin K dependent procoagulant components prothrombin, factor VII, IX, X and also of the coagulation inhibitors protein C and protein S. The kinetics of decrease of the vitamin K dependent factors depends on their specific half-lives and on the dose of the oral anticoagulant drug (Weiss et al, 1987;Kumar et al, 1990). The decrease is induced by a competitive interference of coumarins with enzymes of the vitamin K cycle (Hirsh, 1991).…”

Which Coagulation Factors Interfere with the One-Stage Prothrombin Time?

“…The PT assays differ in types of throm boplastin and dilution which also greatly in fluence their sensitivity and the influence of the protein induced by vitamin K absence inhibitor [2], however, identical results can be obtained by standardization [3], It is believed, at present, that PT reflects all vitamin In dependent coagulation factors [4][5][6][7] except factor IX [8,9],…”