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

Johanna H. H. van Geest-Daalderop; Barbara A. Hutten; Nathalie C. V. Péquériaux; Fred J. L. M. Haas; Marcel Levi; Augueste Sturk

doi:10.1160/TH06-11-0645

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2007; 98(04): 738-746
DOI: 10.1160/TH06-11-0645

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

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

Authors

Johanna H. H. van Geest-Daalderop

¹Department Thrombosis Service of Laboratory of Clinical Chemistry and Haematology, Jeroen Bosch Hospital, ‘s-Hertogenbosch, The Netherlands
Barbara A. Hutten

³Departments of Clinical Epidemiology and Biostatistics, Amsterdam, The Netherlands
Nathalie C. V. Péquériaux

¹Department Thrombosis Service of Laboratory of Clinical Chemistry and Haematology, Jeroen Bosch Hospital, ‘s-Hertogenbosch, The Netherlands
Fred J. L. M. Haas

²Department of Clinical Chemistry and Haematology, Antonius Hospital, Nieuwegein, The Netherlands
Marcel Levi

⁴Departments of Internal Medicine and Academic Medical Center, Amsterdam, The Netherlands
Augueste Sturk

⁵Departments of Clinical Chemistry, Academic Medical Center, Amsterdam, The Netherlands

Abstract

Summary

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 consequences for 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 factorsVII, 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 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.

Keywords

Acenocoumarol - phenprocoumon - INR variation in 24 h - coagulation factor variation in 24 h

Full Text

References

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