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Effects of the oral, direct factor Xa inhibitor rivaroxaban on commonly used coagulation assays.

Hillarp, Andreas LU ; Baghaei, F; Blixter, I F; Gustafsson, K M; Stigendal, L; Sten-Linder, M; Strandberg, Karin LU and Lindahl, T L (2011) In Journal of Thrombosis and Haemostasis 9. p.133-139
Abstract
Introduction: Rivaroxaban is an oral direct factor Xa inhibitor developed for prophylaxis and treatment of thromboembolic disorders. Laboratory monitoring is not necessary but the dose dependent effects on common reagents and assay procedures are largely unknown. Objectives: To investigate the effect of rivaroxaban on commonly used coagulation assays. Material and Methods: Rivaroxaban was added to plasma from healthy subjects in the concentration range 0 -1000 μg/L and analyzed using different reagents for activated partial thromboplastin time (APTT), prothrombin time (PT), antithrombin, fibrinogen and activated protein C (APC) resistance assays. Results: At an expected peak concentration of rivaroxaban in clinical use, the APTTs were... (More)
Introduction: Rivaroxaban is an oral direct factor Xa inhibitor developed for prophylaxis and treatment of thromboembolic disorders. Laboratory monitoring is not necessary but the dose dependent effects on common reagents and assay procedures are largely unknown. Objectives: To investigate the effect of rivaroxaban on commonly used coagulation assays. Material and Methods: Rivaroxaban was added to plasma from healthy subjects in the concentration range 0 -1000 μg/L and analyzed using different reagents for activated partial thromboplastin time (APTT), prothrombin time (PT), antithrombin, fibrinogen and activated protein C (APC) resistance assays. Results: At an expected peak concentration of rivaroxaban in clinical use, the APTTs were almost invariably prolonged but at lower concentrations the effect was weak. The concentration needed to double the APTT varied between 389 ±106 μg/L to 617 ±149 μg/L for different reagents. The PT assays showed a marked degree of difference. In general, the Quick PT type assays were more sensitive compared to the Owren type PT assays. The results from antithrombin assays were dependent on the type of reagent with the Xa-based assay being sensitive for rivaroxaban with an estimated increase of 0.09 IU/mL per 100 μg/L rivaroxaban. There were only minor effects on fibrinogen assays based on thrombin reagents. The APTT-based assay for APC resistance is affected in a dose dependent manner whereas an assay based on the activation of coagulation at the prothrombinase level was unaffected. Conclusions: Different assays, and even different reagents within an assay group, display variable effects by therapeutic concentrations of rivaroxaban. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
Journal of Thrombosis and Haemostasis
volume
9
pages
133 - 139
publisher
Federation of European Neuroscience Societies and Blackwell Publishing Ltd
external identifiers
  • wos:000286055500019
  • pmid:20946166
  • scopus:78650965540
ISSN
1538-7933
DOI
10.1111/j.1538-7836.2010.04098.x
language
English
LU publication?
yes
id
ab33c679-a9c2-4fbd-ab60-70932275be36 (old id 1711172)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20946166?dopt=Abstract
date added to LUP
2010-11-05 15:57:21
date last changed
2017-10-22 04:51:32
@article{ab33c679-a9c2-4fbd-ab60-70932275be36,
  abstract     = {Introduction: Rivaroxaban is an oral direct factor Xa inhibitor developed for prophylaxis and treatment of thromboembolic disorders. Laboratory monitoring is not necessary but the dose dependent effects on common reagents and assay procedures are largely unknown. Objectives: To investigate the effect of rivaroxaban on commonly used coagulation assays. Material and Methods: Rivaroxaban was added to plasma from healthy subjects in the concentration range 0 -1000 μg/L and analyzed using different reagents for activated partial thromboplastin time (APTT), prothrombin time (PT), antithrombin, fibrinogen and activated protein C (APC) resistance assays. Results: At an expected peak concentration of rivaroxaban in clinical use, the APTTs were almost invariably prolonged but at lower concentrations the effect was weak. The concentration needed to double the APTT varied between 389 ±106 μg/L to 617 ±149 μg/L for different reagents. The PT assays showed a marked degree of difference. In general, the Quick PT type assays were more sensitive compared to the Owren type PT assays. The results from antithrombin assays were dependent on the type of reagent with the Xa-based assay being sensitive for rivaroxaban with an estimated increase of 0.09 IU/mL per 100 μg/L rivaroxaban. There were only minor effects on fibrinogen assays based on thrombin reagents. The APTT-based assay for APC resistance is affected in a dose dependent manner whereas an assay based on the activation of coagulation at the prothrombinase level was unaffected. Conclusions: Different assays, and even different reagents within an assay group, display variable effects by therapeutic concentrations of rivaroxaban.},
  author       = {Hillarp, Andreas and Baghaei, F and Blixter, I F and Gustafsson, K M and Stigendal, L and Sten-Linder, M and Strandberg, Karin and Lindahl, T L},
  issn         = {1538-7933},
  language     = {eng},
  pages        = {133--139},
  publisher    = {Federation of European Neuroscience Societies and Blackwell Publishing Ltd},
  series       = {Journal of Thrombosis and Haemostasis},
  title        = {Effects of the oral, direct factor Xa inhibitor rivaroxaban on commonly used coagulation assays.},
  url          = {http://dx.doi.org/10.1111/j.1538-7836.2010.04098.x},
  volume       = {9},
  year         = {2011},
}