During warfarin induction, the Fiix-prothrombin time reflects the anticoagulation level better than the standard prothrombin time

J Thromb Haemost. 2017 Jan;15(1):131-139. doi: 10.1111/jth.13549. Epub 2016 Nov 30.


Essentials Fiix-prothrombin time (PT) monitoring of warfarin measuring factor (F) II and X, is effective. Plasma obtained during warfarin induction and stable phase in Fiix-trial was assayed. Fiix-PT stabilized anticoagulation earlier than monitoring with traditional PT-INR. FVII had little effect on thrombin generation that was mainly determined by FII and FX.

Summary: Background The prothrombin time (PT) is equally prolonged by reduction of each of the vitamin K-dependent (VKD) factors (F) II, VII and X. The Fiix-PT is only affected by FII and FX, the main contributors to thrombin generation (TG). Objective To test the hypothesis that variability in warfarin anticoagulation is reduced early during monitoring with the normalized PT-ratio calculated from Fiix-PT (Fiix-International Normalized Ratio [INR]) compared with traditional PT-INR monitoring. Also, that because of its insensitivity to FVII, Fiix-PT more accurately reflects TG when Fiix-INR and PT-INR are discrepant. Methods Samples from Fiix-trial participants monitored with either Fiix-PT or PT were used. VKD coagulation factors and TG were measured in samples from 40 patients during stable anticoagulation and in serial samples obtained from 26 patients during warfarin induction. TG was assessed in relation to selective reduction in single VKD factors. Results During Fiix-warfarin induction full anticoagulation measured as FII or FX activity was achieved at a similar rate to that with PT-warfarin but subsequently stabilized better. Fiix-INR but not PT-INR mirrored total TG during initiation. During induction, FII (R2 = 0.66) and FX (R2 = 0.52) correlated better with TG and with a steeper slope than did FIX (R2 = 0.37) and in particular FVII (R2 = 0.21). In vitro, FII and FX were the main determinants of TG at concentrations observed during VKA anticoagulation, whereas FVII and FIX had little influence. Conclusions Fiix-PT monitoring reduces anticoagulation variability, suggesting that monitoring FVII has a limited role during VKA management. TG is better reflected by Fiix-PT.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Anticoagulants / therapeutic use*
  • Blood Coagulation / drug effects
  • Blood Coagulation Factors / therapeutic use
  • Blood Coagulation Tests / methods
  • Double-Blind Method
  • Drug Monitoring
  • Factor X / chemistry*
  • Female
  • Hemostatics / therapeutic use
  • Humans
  • International Normalized Ratio
  • Male
  • Middle Aged
  • Prothrombin / chemistry*
  • Prothrombin Time
  • Thrombin / chemistry
  • Vitamin K / chemistry
  • Warfarin / therapeutic use*


  • Anticoagulants
  • Blood Coagulation Factors
  • Hemostatics
  • Vitamin K
  • Warfarin
  • Prothrombin
  • Factor X
  • Thrombin