Thromb Haemost 2012; 107(05): 985-997
DOI: 10.1160/TH11-11-0804
New Technologies, Diagnostic Tools and Drugs
Schattauer GmbH

Impact of dabigatran on a large panel of routine or specific coagulation assays

Laboratory recommendations for monitoring of dabigatran etexilate
Jonathan Douxfils
1  Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for LIfe Sciences (NARILIS), University of Namur, Belgium
,
François Mullier
1  Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for LIfe Sciences (NARILIS), University of Namur, Belgium
2  Hematology Laboratory, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for LIfe Sciences (NARILIS), CHU Mont-Godinne, Université Catholique de Louvain, Belgium
,
Séverine Robert
1  Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for LIfe Sciences (NARILIS), University of Namur, Belgium
,
Christian Chatelain
3  Hematology Department, Namur Thrombosis and Hemostasis Center, CHU Mont-Godinne, Université Catholique de Louvain, Belgium
,
Bernard Chatelain
2  Hematology Laboratory, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for LIfe Sciences (NARILIS), CHU Mont-Godinne, Université Catholique de Louvain, Belgium
,
Jean-Michel Dogné
1  Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for LIfe Sciences (NARILIS), University of Namur, Belgium
› Author Affiliations
Further Information

Publication History

Received: 21 November 2011

Accepted after minor revision: 08 February 2012

Publication Date:
25 November 2017 (online)

Summary

Due to low bioavailability and high inter-individual variability, monitoring of dabigatran may be required in specific situations to prevent the risk of bleedings or thrombosis. The aim of the study was to determine which coagulation assay(s) could be used to assess the impact of dabig-atran on secondary haemostasis. Dabigatran was spiked at concentrations ranging from 4.7 ng/ml to 943.0 ng/ml in pooled citrated human platelet-poor plasma. The following clotting assays were performed: prothrombin time (PT); activated partial thromboplastin time (aPTT); thrombin time (TT); ecarin clotting time (ECT); ecarin chromo-genic assay (ECA); prothrombinase-induced clotting time (PiCT); activated clotting time (ACT); Hemoclot Thrombin Inhibitor (HTI) and thrombin generation assay (TGA). A concentration-dependent prolongation of PT, dPT, and aPTT was observed with aPTT being the more sensitive test. The results varied mostly due to the clotting reagent. HTI, ECT and TGA were the most sensitive tests but are not available 24 hours a day. In addition, HTI showed a linear correlation with a good reproduci-bility. Dabigatran induced a concentration-dependent delay and inhibition of tissue factor-induced TGA. Cut-offs related with higher risk of bleedings or thrombosis were defined for each reagent of aPTT and HTI. In conclusion, aPTT could be used for the monitoring of dabigatran and as screening test for the risk of overdose. However, because of its higher sensitivity, good reproducibility, excellent linear correlation at all doses, its simplicity of use, and possibilities of automation, HTI should be considered as the gold-standard.

Contributed equally to this work (as first authors and last authors, respectively).