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

Hillarp, Andreas LU ; Strandberg, Karin LU ; Baghaei, Fariba; Fagerberg Blixter, Inger; Gustafsson, Kerstin M. and Lindahl, Tomas L. (2018) In Scandinavian Journal of Clinical and Laboratory Investigation 78(7-8). p.575-583
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,... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
activated partial thromboplastin time, Anticoagulants, blood coagulation analysis, edoxaban, lupus coagulation inhibitor, prothrombin time
in
Scandinavian Journal of Clinical and Laboratory Investigation
volume
78
issue
7-8
pages
575 - 583
publisher
Informa Healthcare
external identifiers
  • scopus:85054381039
ISSN
0036-5513
DOI
10.1080/00365513.2018.1522664
language
English
LU publication?
yes
id
b0aa5ba6-100b-4685-8e27-a20d14790f0f
date added to LUP
2018-11-13 14:47:05
date last changed
2019-08-14 04:27:00
@article{b0aa5ba6-100b-4685-8e27-a20d14790f0f,
  abstract     = {<p>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.</p>},
  author       = {Hillarp, Andreas and Strandberg, Karin and Baghaei, Fariba and Fagerberg Blixter, Inger and Gustafsson, Kerstin M. and Lindahl, Tomas L.},
  issn         = {0036-5513},
  keyword      = {activated partial thromboplastin time,Anticoagulants,blood coagulation analysis,edoxaban,lupus coagulation inhibitor,prothrombin time},
  language     = {eng},
  month        = {11},
  number       = {7-8},
  pages        = {575--583},
  publisher    = {Informa Healthcare},
  series       = {Scandinavian Journal of Clinical and Laboratory Investigation},
  title        = {Effects of the oral, direct factor Xa inhibitor edoxaban on routine coagulation assays, lupus anticoagulant and anti-Xa assays},
  url          = {http://dx.doi.org/10.1080/00365513.2018.1522664},
  volume       = {78},
  year         = {2018},
}