Relationship of Edoxaban Plasma Concentration and Blood Coagulation in Healthy Volunteers Using Standard Laboratory Tests and Viscoelastic Analysis

Abstract

The capability of viscoelastic measurement parameters to screen anticoagulation activity of edoxaban in relation to its plasma concentrations was evaluated in 15 healthy male volunteers. Blood samples were drawn before the oral administration of edoxaban 60 mg and 2, 4, 6, 8, and 24 hours after administration. At each time, standard coagulation tests were performed, blood viscoelastic properties were measured with a thromboelastometry device ROTEM delta analyzer (Instrumentation Laboratory, Werfen, Barcelona, Spain), and edoxaban plasma concentrations were measured. Our primary interest was the possible correlation between edoxaban plasma concentrations and values for ROTEM ExTEM, and FibTEM. We also studied the correlation of edoxaban plasma concentrations with the results of standard coagulation tests. We saw the effect of a single dose of edoxaban most clearly in clotting time (CT) of ROTEM ExTEM and FibTEM. Changes in these parameters correlated significantly with edoxaban plasma concentrations up to 6 hours from the ingestion of the drug. Activated partial thromboplastin time, prothrombin time, and anti–factor Xa were also affected. Peak changes were observed 2 and 4 hours after administration of edoxaban. The changes were mostly reversed after 8 hours. In conclusion, ROTEM CT correlates significantly with edoxaban plasma concentrations and can be used to estimate the effect of edoxaban. ROTEM should be considered as part of the assessment of coagulation, with the big advantage of being readily available on site.

“In Less than No Time”: Feasibility of Rotational Thromboelastometry to Detect Anticoagulant Drugs Activity and to Guide Reversal Therapy

“…Several studies pointed out that thromboelastometric tests were applicable to qualitatively monitor the anticoagulant effect of DOACs [ 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 , 152 , 153 , 154 , 155 , 156 , 157 , 158 , 159 , 160 , 161 , 162 , 163 , 164 ] ( Table S3 in Supplementary Materials ) and the reversibility of their activity [ 165 , 166 , 167 , 168 , 169 , 170 , 171 , 172 , 173 , 174 , 175 , 176 , 177 ].…”

“…Data regarding the use of ROTEM for the evaluation of patients anticoagulated with edoxaban are very limited. Two studies considered the impact of whole blood spikes with edoxaban on the ROTEM assay [ 151 , 164 ]. Seyve et al [ 151 ] reported INTEM-CT to be less sensitive than EXTEM-CT; moreover, EXTEM-CT was above the normal range when the plasma concentrations of edoxaban were about 100 ng/mL.…”

“…Seyve et al [ 151 ] reported INTEM-CT to be less sensitive than EXTEM-CT; moreover, EXTEM-CT was above the normal range when the plasma concentrations of edoxaban were about 100 ng/mL. Havrdova et al, [ 164 ] in 15 healthy volunteers, analyzed the relationship between viscoelastic parameters and edoxaban plasma concentration after 60 mg of edoxaban oral administration. The authors found changes in EXTEM-CT and FIBTEM-CT.…”

The impact of direct oral anticoagulants on viscoelastic testing – A systematic review

“…Six studies ( 25 , 29 , 38 , 45 , 46 , 55 ) were identified analyzing the effects if edoxaban on viscoelastic testing ( Supplementary Tables 2.1–2.3 ). The CT and R in relation to the edoxaban plasma concentration are shown in Figure 4 .…”

“…By the time literature review was concluded there were only two studies assessing the effects of edoxaban on ROTEM showing significant prolongations of EXTEM clotting time (CT) even in therapeutic doses ( 45 , 55 ) ( Table 2.1 ).…”