title: Impact of dabigatran on a large panel of routine or specific coagulation assays. Laboratory recommendations for monitoring of dabigatran etexilate.
abstract: 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 dabigatran 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 chromogenic 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 reproducibility. 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.
authors.affiliation: Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for LIfe Sciences (NARILIS), University of Namur, Belgium.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Douxfils
authors.forename: François
authors.initials: F
authors.lastname: Mullier
authors.forename: Séverine
authors.initials: S
authors.lastname: Robert
authors.forename: Christian
authors.initials: C
authors.lastname: Chatelain
authors.forename: Bernard
authors.initials: B
authors.lastname: Chatelain
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Dogné
mesh_terms: D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests; D000069604:Dabigatran; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods*; D010450:Endopeptidases; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D016014:Linear Models; D010314:Partial Thromboplastin Time; D011237:Predictive Value of Tests; D011517:Prothrombin Time; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D015203:Reproducibility of Results; D018570:Risk Assessment; D012307:Risk Factors; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000378:metabolism; D013918:Thrombin Time; D014914:Whole Blood Coagulation Time
chemical_list: D000925:Anticoagulants; D001562:Benzimidazoles; D011725:Pyridines; D010450:Endopeptidases; D013917:Thrombin; C020097:ecarin; D000069604:Dabigatran