The influence of coagulation factors on the in-treatment biological variation of international normalized ratio for patients on warfarin

Abstract

Background. Biological variation is usually estimated in healthy individuals during steady-state conditions. The aim of this study was to estimate the in-treatment biological variation of the International normalised ratio (INR) and to investigate to what extent the different levels of coagulation factors could explain this variation. Methods. Blood samples were collected from randomly included patients on warfarin treatment. INR was determined on a laboratory instrument (STA Compact^®) and on three point-of-care instruments (Simple Simon^®PT, CoaguChek^®XS and INRatio^™). The level of fibrinogen, and the activity of coagulation factors II, V, VII and X were determined. Results. The in-treatment within- and between-subject coefficients of variation of INR were dependent on the method and varied between 18 and 24% and 13 and 19%, respectively, and were reduced to 3.9–5.1% and 2.3–5.8%, after correction for coagulation factors which could explain 91–95% of the variance of INR. Conclusions. The in-treatment biological variation of INR was higher than reported for healthy individuals as well as patients in a steady-state condition, but by correcting for appropriate coagulation factors it was reduced. The association between INR and coagulation factors was different for the different PT methods mainly due to different sensitivity towards FII and FVII.

Key Words::

• International normalised ratio (INR)
• ANOVA
• point-of-care system
• blood coagulation factor
• warfarin

Acknowledgements

The authors thank Solveig Heimark for help with the recruitment of patients, and Marianne Wettergreen, Trine Andreassen, Solveig Vannes, Kjersti Østrem, Eli Skare and Marthe Hammersland for excellent technical assistance. Thanks to all patients for their participations. Gratitude is expressed to Zafena AB, Roche Diagnostics and Bergman Diagnostika for loan of POC-instruments.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.