The laboratory's 2015 perspective on direct oral anticoagulant testing

Abstract

Summary. The introduction of direct oral anticoagulant (DOAC) therapy into clinical use in the past 5 years has had significant impact on the clinical laboratory. Clinicians' desire to determine plasma drug presence or measure drug concentration, and more recent observations regarding the limitations and utility of coagulation testing in the setting of DOAC treatment, suggest that early published recommendations regarding laboratory testing should be reassessed. These initial recommendations, furthermore, were often based on drug-spiked plasma studies, rather than samples from patients receiving DOAC therapy. We have demonstrated that reagent sensitivity varies significantly whether drug-spiked samples or samples from DOAC-treated patients are tested. Data from drug-enriched samples must therefore be interpreted with caution or be used as a guide only. We present laboratory assays that can be used to determine drug presence and to measure drug concentration, and provide recommended testing algorithms. As DOAC therapy may significantly impact on specialty coagulation assays, we review those tests with the potential to give false-positive and false-negative results.

Dissociation between the pharmacokinetics and pharmacodynamics of once‐daily rivaroxaban and twice‐daily apixaban: a randomized crossover study

“…During the time period 0-12 h after the last dose of rivaroxaban and the morning dose of apixaban, the inhibitory effects of rivaroxaban on ETP relative to baseline were significantly greater than those of apixaban (AUC 0-12 , 6.36 h for rivaroxaban and 8.69 h for apixaban; Table S1). In the time period 12-24 h after the last dose of rivaroxaban and 0-12 h after the last (evening) dose of apixaban (AUC [12][13][14][15][16][17][18][19][20][21][22][23][24] ), the effects of rivaroxaban and apixaban on inhibition of ETP were similar (Table S1). Rivaroxaban also showed significantly greater suppression of the peak of thrombin generation during the 0-24-h dosing interval (AUC 0-24 , 6.59 h for rivaroxaban and 7.84 h for apixaban; Fig.…”

“…3B; Table S1). Furthermore, the effects of rivaroxaban on prolongation of thrombin generation lag time and prolongation of the time to the peak of thrombin generation were significantly greater than those of apixaban for all measured parameters (E max , AUC 0-12 , AUC [12][13][14][15][16][17][18][19][20][21][22][23][24] , and AUC 0-24 ; Figs 4 and 5; Table S1). At time points 36 h and 48 h after the last dose of rivaroxaban (equivalent to 24 h and 36 h after the last dose of apixaban), the inhibitory effects of rivaroxaban on the peak and time to peak of thrombin generation were significantly greater than those of apixaban (Table S2).…”

“…AUC 0-12 represents the time period 0-12 h after the last dose of rivaroxaban and the morning dose of apixaban, AUC [12][13][14][15][16][17][18][19][20][21][22][23][24] represents the time periods 12-24 h after the last dose of rivaroxaban and 0-12 h after the evening dose of apixaban and AUC 0-24 represents the 24-h time period after the last dose of rivaroxaban and the morning dose of apixaban. Relative changes from baseline were investigated for all PD parameters, except anti-FXa activity, for which absolute values were evaluated.…”

Thrombophilia Work-up in Females with Venous Thromboembolism in Association with Oral Contraceptive Use: Results, Strategy and Clinical Application of Testing

“…However, we recommend these tests after cessation of DOAC therapy, because of potential underlying deficiencies can be masked [15]. Clinical data are shown in following tables but the analysis is largely discussed elsewhere [16].…”

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].…”