Point-of-care testing of coagulation in patients treated with edoxaban

Abstract

Edoxaban, alongside other direct oral anticoagulants (DOAC), is increasingly used for prevention of thromboembolism, including stroke. Despite DOAC therapy, however, annual stroke rate in patients with atrial fibrillation remains 1-2%. Rapid exclusion of relevant anticoagulation is necessary to guide thrombolysis or reversal therapy but, so far, no data exists on the effect of edoxaban on available point-of-care test systems (POCT). To complete our previous investigation on global coagulation-POCT for the detection of DOAC, we evaluated whether CoaguChek®-INR (CC-INR) is capable of safely ruling out edoxaban concentrations above the current treatment thresholds of 30/50 ng/mL in a blood sample. We studied patients receiving a first dose of edoxaban; excluding subjects receiving other anticoagulants. Six blood samples were collected from each patient: before drug intake, 0.5, 1, 2 and 8 h after intake, and at trough (24 h). CC-INR and mass spectrometry for edoxaban concentrations were performed for each time-point. One hundred and twenty blood samples from 20 patients contained 0-302 ng/mL of edoxaban. CC-INR ranged from 0.9 to 2.3. Pearson's correlation coefficient showed strong correlation between CC-INR and edoxaban concentrations (r = 0.73, p < 0.001). Edoxaban concentrations > 30 and > 50 ng/mL were ruled out by CC-INR ≤ 1.0 and ≤ 1.1, respectively, with high specificity (> 95%), and a sensitivity of 44% (95%-confidence interval: 30-59%) and 86% (74-93%), respectively. Our study represents the first evaluation of coagulation-POCT in edoxaban-treated patients. CC-POCT is suitable to safely exclude clinically relevant edoxaban concentrations prior to thrombolysis, or guide reversal therapy in stroke patients.

Keywords: Anticoagulation reversal; CoaguChek; DOAC; Point-of-care; Stroke; Thrombolysis.

Conflict of interest statement

F. Härtig and M. Ebner received reimbursement for congress traveling from Bayer. I. Birschmann received speaker’s honoraria from Aspen Germany, Bristol-Myers Squibb/Pfizer, Siemens Healthcare, and CSL Behring, and reimbursement for congress traveling from aspen and Bristol-Myers Squibb, and performed contract research for Siemens Healthcare. Ingvild Birschmann is a member of the advisory board of LFB biomedicaments. U. Ziemann received grants from German Research Foundation, German Federal Ministry of Education and Research, European Research Council, Bristol-Myers Squibb, Janssen Pharmaceuticals, Servier, and Biogen Idec, and consulting honoraria from Pfizer, Bayer Vital, and CorTec (all outside of the present work). S. Poli received speaker’s/consulting honoraria from Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb/Pfizer, Daiichi Sankyo, and Werfen, reimbursement for congress traveling from Bayer, and Boehringer-Ingelheim, and research support from Bristol-Myers Squibb/Pfizer, Boehringer-Ingelheim, Daiichi Sankyo, and Helena Laboratories (all outside of the present work). The other authors (A. Peter, S. Hörber, M. Sonnleitner, C. Spencer, P. Bombach, M.-I. Stefanou, J. Kuhn, and A. Mengel) report no conflicts of interest.

Figures

Fig. 1

a Correlation of CoaguChek®-international normalized ratio (CC-INR) values and edoxaban plasma concentrations (dashed line: regression line), b changes in edoxaban plasma concentrations and CC-INR results over the course of the study period (displayed as mean ± one standard deviation), c percentage of edoxaban plasma concentrations below and above the treatment-relevant thresholds of 30 and 50 ng/mL found at different CC-INR levels, and d receiver operating characteristics curve found for CC-INR when testing for detection of samples containing edoxaban plasma concentrations ≤ 30 and ≤ 50  ng/mL

Fig. 2

a Percentage of rivaroxaban plasma concentrations below and above the treatment-relevant thresholds of 30 and 50 ng/mL found at different level of CoaguChek®-international normalized ratio (CC-INR), and b receiver operating characteristics curve found for CC-INR when testing for detection of samples containing rivaroxaban plasma concentrations ≤ 30 and ≤ 50 ng/mL

Fig. 3

Proposed algorithm for emergency coagulation assessment using the CoaguChek® point-of-care test system (POCT) for rapid decision making in edoxaban and rivaroxaban-treated patients. CC-INR CoaguChek®-international normalized ratio, DOAC direct oral anticoagulant, ICH intracranial hemorrhage