A New Generation Prothrombin Time Method for INR

The Open Medicinal Chemistry Journal 27 Feb 2008 RESEARCH ARTICLE DOI: 10.2174/1874104500802010011


Prothrombin time (PT) is the leading test for monitoring oral anticoagulation therapy (OAT). We sought to determine INR taking into account only active coagulation factors FII, FVII and FX without inhibition in patient plasmas and calibrator kits.

We measured PT using a combined thromboplastin reagent. The calculation was based on a new PT method, which measures active coagulation factors (F II, F VII, FX) and corrects the errors caused by inactive coagulation factors.

On this basis, an INR result with and without inhibition for individual patient samples was also calculated and applied to 200 plasma samples obtained from OAT patients. Conspicuous variation in inhibition between the four calibration kits was noted. The kinetics of this inhibition was closest to a noncompetitive pattern.

The need of correction for INRs of single patients increases with higher INRs. At the same level of patient INRs the coagulation inhibiton varies markedly.

It has been known that different thromboplastin reagents possess variable sensitivities, but this may depend on sensitivity in inactive coagulation factors. PT methods today measure the sum of active coagulation factors and inhibition of inactive coagulation factors. ISI calibrators contain variable amounts of inactive coagulation factors, which renders harmonisation of INR results.

Application of the Acf-PT (INRAcf) presented in this work develops the PT methodology to measure the true coagulation activity in vivo for patient warfarin therapy without inhibition. INRInh can evidently also be used for the diagnostics and follow-up of certain liver diseases.

Keywords: PT, prothrombin time, oral anticoagulant therapy, Pivka.
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