The influence on INRs and coagulation factors of the time span between blood sample collection and intake of phenprocoumon or acenocoumarol:: Consequences for the assessment of the dose

Managing treatment with vitamin K antagonists, the prothrombin time (PT),expressed as international normalized ratio (INR), may not represent the INR during the entire 24 hour (h) period, and this variation may be different between long-acting phenprocoumon and short-acting acenocoumarol. For both drugs we investigated the variation in 24 h of the PT/lNR, the consequences for the assessment of the doses and which vitamin K-dependent factor causes the daily variation. Patients on selfmanagement took their medication at 6 p.m. and determined their INRs for eight weeks, once a week and three times daily (8.30 a.m.,6 p.m. and 11 p.m.,thus 14.5 h,24 h and 29 h after taking the medication, respectively). Acenocoumarol showed a significant variation in INRs over the 24 h period,with 22 out of 80 INRs >20% lower at 11 p.m. versus 8.30 a.m. Phenprocoumon showed only few variations. Patients managed by the anticoagulation clinic took their medication at 6 p.m. for four weeks and then at 8 a.m. for four weeks, 15 h and 25 h, respectively, before the weekly blood collection. PT/INR and coagulation factorsVII, X and 11 were determined. With acenocoumarol, taken 25 h before blood collection, the INRs were significantly different compared to 15 h, especially attributed to plasma levels of factorVII. Those on phenprocoumon were equal. These variations of INRs during 24 h may have major effects on the prescribed dose of short-acting vitamin K antagonists, such as acenocoumarol, especially for INRs at the limits of the therapeutic ranges.