Behaviour of Factors II, VII, IX, and X during Long-Term Treatment with Coumarin

Abstract

SummaryDuring long-term treatment with the long-acting coumarin derivative phenprocoumarol (marcoumar) no statistically significant difference in the depression of the activity of coagulation factors II, VII, IX, and X was found. The shorter-acting anticoagulants acenocoumarol (sintrom), warfarin sodium (coumadin), and dicoumarol, possibly lower factor IX somewhat less and factor X somewhat more than they do factors II and VII.A 2.5-fold prolongation of the “prothrombin” time (using Owren 5 s human brain thromboplastin) and the same prolongation of the thrombotest time appear to correspond with a depression of all four factors from 100% down to approximately 20’%, the normal standard being a mixed population with a mean age of 29 years.Separate determination of one of the four coagulation factors concerned is pointless; “prothrombin” time estimation, and more specifically thrombotest, still remain the most reliable methods for controlling the anti-vitamin K action of anticoagulants during long-term treatment.

Inter‐relationship among individual vitamin K‐dependent clotting factors at different levels of anticoagulation.

“…This observation confirms the earlier findings at a therapeutic level of anticoagulation (e.g. Loeliger et al, 1963) and the postulate that warfarin acts to depress synthesis of the vitamin K-dependent clotting factors through a common mechanism involving vitamin K (Suttie, 1980). These findings suggest, at steady state, that the activity of any one clotting factor can serve to reflect the activities of the others.…”

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

“…The second most re duced coagulation factors in warfarin-treated patients were IX and X while II was least reduced. These results agree with those of Owren [ 14] and Kazmier et al [8]; others have found equal reduction of all vitamin Inde pendent factors [4,7], greatest reduction of II and X [6] or II [5]. The vitamin K-dependent factors may be more alike at extreme antico agulation [4], but cases beyond therapeutic levels (TT < 0.05 equal to INR > 4.3) [3] were not included in the present study.…”

“…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],…”

Mechanism of the anticoagulant effect of warfarin as evaluated in rabbits by selective depression of individual procoagulant vitamin K-dependent clotting factors.

“…3). We infer from this experimental result that the fall in plasma factor VII activity in patients treated with warfarin, e.g., to the 20% level observed in a group of patients stably anticoagulated with a vitamin K antagonist (26), contributes little if any to warfarin's antithrombotic efficacy.…”