Performance of coagulation tests in patients on therapeutic doses of dabigatran: a cross‐sectional pharmacodynamic study based on peak and trough plasma levels

Abstract

S. Performance of coagulation tests in patients on therapeutic doses of dabigatran: a cross-sectional pharmacodynamic study based on peak and trough plasma levels. J Thromb Haemost 2013; 11: 1493-1502.Summary. 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 À1. 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).

Determination of dabigatran in plasma, serum, and urine samples: comparison of six methods

“…This is in agreement with other studies reporting on the lower suitability of the APTT for the determination of dabigatran [17,19,35]. APTT and PiCT are global coagulation assays that may be influenced by many biological factors and assay-specific components [36].…”

Plasma levels of direct oral anticoagulants in real life patients with atrial fibrillation: Results observed in four anticoagulation clinics

“…DOAC inter-individual variability has been inconsistently evaluated in published reports and guidelines, and differently commented as being either low or high [5][6][7][8][9][10][11][12][13][14]. Furthermore, few studies investigated all the DOAC currently licensed for treatment of patients with atrial fibrillation.…”

“…With this in mind it was assumed the anticoagulant effect was prevalently controlled by these conditions. DOAC intra-and inter-individual variability has been previously reported [5][6][7][8][9][10][11][12][13][14], but its magnitude is still considered negligible for management. Furthermore, DOAC showed inter-individual variability of plasma concentration at steady state regardless of type of drug and patient characteristic such as renal function and body weight [9].…”

Direct Oral Anticoagulants in Patients with Thrombophilia: Challenges in Diagnostic Evaluation and Treatment

“…A normal standard TT can exclude the presence of dabigatran in a sample [67]. Dabigatran can be quantified using a chromogenic ecarin assay, ecarin clotting time or a modified (dilute) TT, where excessive sensitivity is overcome by lower concentrations of heparin or sample dilution [60,68]. Since FXa is not involved in fibrinogen conversion into fibrin, the TT is not affected by direct FXa inhibitors [48,64].…”