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Effects of the oral, direct thrombin inhibitor dabigatran on five common coagulation assays

Journal: Thrombosis and Haemostasis
ISSN: 0340-6245
DOI: https://doi.org/10.1160/TH10-06-0342
Issue: 2011: 105/2 (Feb) pp. 207-386
Pages: 371-378

Effects of the oral, direct thrombin inhibitor dabigatran on five common coagulation assays

T. L. Lindahl (1), F. Baghaei (2), I. Fagerberg Blixter (3), K. M. Gustafsson (1), L. Stigendal (2), M. Sten-Linder (4), K. Strandberg (5), A. Hillarp (5); and from the expert group on coagulation of the External Quality Assurance in Laboratory Medicine in Sweden

(1) Department of Clinical and Experimental Medicine, Clinical Chemistry, University of Linköping, Sweden; (2) Department of Medicine, Coagulation Centre, Sahlgrenska University Hospital, Gothenburg, Sweden; (3) Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine, The Sahlgrenska Academy, University of Gothenburg, Sweden; (4) Department of Molecular Medicine and Surgery, Clinical Chemistry, Karolinska Institutet, Stockholm, Sweden; (5) University and Regional Laboratories Region Scania, Clinical Chemistry, Malmö, Sweden

Keywords

thrombin inhibitor, Interference, anticoagulant, coagulation assays, dabigatran

Summary

Dabigatran is an oral, reversible thrombin inhibitor that has shown promising results in large clinical trials. Laboratory monitoring is not needed but the effects on common coagulation assays are incompletely known. Dabigatran was added to plasma from healthy subjects in the concentration range 0–1,000 μg/l and analysed using several reagents for activated thromboplastin time (APTT), prothrombin time (PT), fibrinogen, antithrombin, and activated protein C resistance. Typical trough concentrations are about 50 μg/l, peak concentrations 100–300 μg/l. At 100 μg/l all APTT-results were prolonged. The concentration required to double APTT ranged between 227 and 286 μg/l, the responses for all five reagents were similar. PT-reagents were much less affected with almost no samples above INR 1.2 at 100 μg/l. The effect was sample dilution dependent with PT Quick type more sensitive than PT Owren type methods. If a patient on dabigatran has prolonged APTT, >90 seconds, and Quick PT INR>2 or Owren PT INR>1.5 over-dosing or accumulation of dabigatran should be considered. Two of four fibrinogen reagents underestimated the fibrinogen concentration considerably at expected peak concentration. Methods based on inhibition of thrombin over-estimated the antithrombin concentration, but not Xa-based. The APC-resistance methods over-estimated the APC-ratio, which may lead to miss-classification of factor V Leiden patients as being normal. Different coagulation assays, and even different reagents within an assay group, display variable effects at therapeutic concentrations of dabigatran. Some of these assay variations are of clinical importance, thus knowledge is needed for a correct interpretation of results.

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