2. INTRODUCTION AND RATIONALE 2.1 Background Vitamin K antagonists (VKA, coumarins) are orally active anticoagulants that prevent normal gamma carboxylation of the vitamin K dependent coagulation factors (FII, FVII, FIX, FX). The consequence is a reduction in the clotability of the blood, ie an anticoagulant effect that can be used therapeutically for the purpose of preventing thromboembolism. In order to assure efficacy and safety, the dose of VKA needs to be adjusted to maintain the normalized prothrombin time ratio (international normalized ratio, INR) within a safe therapeutic range (most often with INR target 2.5, range 2.0-3.0). The clotting times obtained with PT based tests have in practice for over 50 years been presumed to directly reflect the antithrombotic effect of VKA in patients (Loeliger 1984). The PT (or P&P-test) are used all over the world for the purpose of monitoring anticoagulation and to make dose-adjustments in patients taking VKA. Their results have been standardized by calculating the International Normalized Ratio (INR) which takes into account the sensitivity (strength) of the thromboplastin used by different reagents.