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/INR, the consequencesfor the assessment of the doses and which vitamin K-dependent factor causes the daily variation. Patients on self-management 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 factors VII, X and II 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 factor VII. 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