title: Performance of coagulation tests in patients on therapeutic doses of dabigatran: a cross-sectional pharmacodynamic study based on peak and trough plasma levels.
abstract: BACKGROUND
  Knowledge of anticoagulation status during dabigatran therapy may be desirable in certain clinical situations.
  
  
  OBJECTIVE
  To determine the coagulation tests that are most useful for assessing dabigatran's anticoagulant effect.
  
  
  METHODS
  Peak and trough blood samples from 35 patients taking dabigatran 150 mg twice daily, and one sample each from 30 non-anticoagulated individuals, were collected. Mass spectrometry and various coagulation assays were performed. 'Therapeutic range' was defined as the range of plasma dabigatran concentrations determined by mass spectrometry between the 2.5th and 97.5th percentiles of all values.
  
  
  RESULTS
  The therapeutic range was 27-411 ng mL(-1) . The prothrombin time (PT) and activated partial thromboplastin time (APTT), determined with multiple reagents, and activated clotting time (ACT) were insensitive to therapeutic dabigatran: 29%, 18% and 40% of samples had a normal PT, APTT, and ACT, respectively. However, normal PT, ACT and APTT ruled out dabigatran levels above the 75th percentile. The thrombin clotting time (TCT) correlated well and linearly with dabigatran levels below the 50th percentile, but was unmeasurable above it. The dilute thrombin time, ecarin clotting time and ecarin chromogenic assay showed linear correlations with dabigatran levels over a broad range, and identified therapeutic and supratherapeutic levels.
  
  
  CONCLUSIONS
  The prothrombin time, APTT and ACT are often normal in spite of therapeutic dabigatran plasma levels. The TCT is useful for detecting minimal dabigatran levels. The dilute thrombin time and chromogenic and clotting ecarin assays accurately identify therapeutic and supratherapeutic dabigatran levels. This trial is registered at www.clinicaltrials.gov (#NCT01588327).
authors.affiliation: Department of Pharmacy, School of Medicine, Department of Family Medicine, University of North Carolina, Chapel Hill, NC 27599, USA. ehawes@unch.unc.edu
authors.forename: E M
authors.initials: EM
authors.lastname: Hawes
authors.forename: A M
authors.initials: AM
authors.lastname: Deal
authors.forename: D
authors.initials: D
authors.lastname: Funk-Adcock
authors.forename: R
authors.initials: R
authors.lastname: Gosselin
authors.forename: C
authors.initials: C
authors.lastname: Jeanneret
authors.forename: A M
authors.initials: AM
authors.lastname: Cook
authors.forename: J M
authors.initials: JM
authors.lastname: Taylor
authors.forename: H C
authors.initials: HC
authors.lastname: Whinna
authors.forename: A M
authors.initials: AM
authors.lastname: Winkler
authors.forename: S
authors.initials: S
authors.lastname: Moll
mesh_terms: D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000494:pharmacology*; D000991:Antithrombins / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D000069604:Dabigatran; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D011446:Prospective Studies; D011517:Prothrombin Time; D013918:Thrombin Time; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D001562:Benzimidazoles; D015091:beta-Alanine; D000069604:Dabigatran
keywords: anticoagulants; blood coagulation; blood coagulation tests; coagulation; dabigatran; drug monitoring