Effects of the oral, direct factor Xa inhibitor edoxaban on routine coagulation assays, lupus anticoagulant and anti-Xa assays

Abstract

Edoxaban is an oral direct factor Xa inhibitor for prophylaxis and treatment of thromboembolic disorders. The effects on common coagulation assays are clinically valuable information and in certain clinical situations a quick assessment of the anticoagulant is wanted. Our aim was to investigate the effect of edoxaban on routine coagulation methods and evaluate anti-Xa assays, commonly used for other direct factor Xa inhibitors, for estimation of the drug concentration. Edoxaban was spiked to plasma samples from healthy subjects in the concentration range 0–742 µg/L and analyzed using different reagents for activated partial thromboplastin time (APTT) and prothrombin time (PT). Assays for antithrombin, activated protein C resistance, lupus anticoagulant (LA) and chromogenic anti-Xa assays were also included. Edoxaban displayed similar effects in vitro to other oral direct Xa inhibitors. The concentration needed to double the coagulation time varied between assays and reagents; 539–758 µg/L for the APTT and between 329 and 2505 µg/L for the PT. Edoxaban gave false high antithrombin activities in assays based on Xa-inhibition. Two integrated assays for LA, both based on activation with dilute Russell’s viper venom, displayed different results. Chromogenic anti-Xa assays displayed linear dose-response curves with edoxaban up to approximately 500 µg/L. In conclusion, therapeutic concentrations of edoxaban variably affect different coagulation assays, and even different reagents within an assay group. In comparison with other oral Xa-inhibitors, the in vitro effects of edoxaban were more similar to rivaroxaban than apixaban. For measurement of edoxaban concentration in plasma, it is possible to use the chromogenic anti-Xa assays.

Keywords:

• Anticoagulants
• blood coagulation analysis
• edoxaban
• lupus coagulation inhibitor
• activated partial thromboplastin time
• prothrombin time

Acknowledgments

The expert technical assistance of the following biomedical scientists is gratefully acknowledged: Peter Nemeczek (Halmstad); Ewa Lönn Karlsson (Linköping); Heidi Isacson (Malmö). Daiichi-Sankyo provided the drug edoxaban. Special thanks to the QC-team at Stago for verification of the edoxaban content in our working solutions. We are also thankful for all support from Mrs Anne Frösegård, Elisabeth Eriksson Boija and Dr Gunnar Nordin at the EQUALIS office in Uppsala.

Disclosure statement

No potential conflict of interest was reported by the author.