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Impact of direct oral anticoagulants on ROTEM® variables; a sample size-calculated experimental study

Sunnersjö, Lotta LU ; Lindquist, Lukas ; Schött, Ulf LU ; Hillarp, Andreas LU ; Undén, Johan LU and Kander, Thomas LU orcid (2024) In Scandinavian Journal of Clinical and Laboratory Investigation 84(7-8). p.540-546
Abstract

Direct oral anticoagulants (DOAC) are increasingly common, with bleeding events associated with elevated plasma concentrations. Rotational thromboelastometry (ROTEM), a point-of-care tool for assessing secondary hemostasis, has demonstrated a correlation with increasing concentrations of DOAC. However, previous studies have only partially explored this relationship. The primary aim in the current study was to investigate the impact of increasing rivaroxaban concentrations on clotting time (CT) in the EXTEM assay. The secondary aims were to investigate the impact of increasing rivaroxaban concentrations on clot formation time (CFT) and α-angle (AA) and to investigate the impact of increasing concentrations of dabigatran and apixaban on... (More)

Direct oral anticoagulants (DOAC) are increasingly common, with bleeding events associated with elevated plasma concentrations. Rotational thromboelastometry (ROTEM), a point-of-care tool for assessing secondary hemostasis, has demonstrated a correlation with increasing concentrations of DOAC. However, previous studies have only partially explored this relationship. The primary aim in the current study was to investigate the impact of increasing rivaroxaban concentrations on clotting time (CT) in the EXTEM assay. The secondary aims were to investigate the impact of increasing rivaroxaban concentrations on clot formation time (CFT) and α-angle (AA) and to investigate the impact of increasing concentrations of dabigatran and apixaban on CT, CFT and AA. Blood from 12 healthy volunteers was spiked to anticipated concentrations of rivaroxaban, dabigatran and apixaban at 0, 50, 100, 200, 500 and 1000 µg/L each. Blood with these varying concentrations was analyzed in four different ROTEM assays and CT, CFT and AA were extracted. CT increased linearly with increasing concentrations of all three DOACs. Rivaroxaban and dabigatran spiked blood showed an increase in CT-EXTEM for the 200–1000µg/L concentrations, compared to baseline, and apixaban for the 500–1000 µg/L concentrations. CFT and AA were affected only in supratherapeutic concentrations for all tested DOACs and primarily in the INTEM assay. Among the tested DOACs, apixaban demonstrated the least impact on CT across all assays. In conclusion, ROTEM-derived CT measurements can serve as surrogate markers for DOAC concentrations.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
anticoagulants, apixaban, dabigatran, Dose–response relationship, hemostasis, rivaroxaban, thromboelastometry
in
Scandinavian Journal of Clinical and Laboratory Investigation
volume
84
issue
7-8
pages
7 pages
publisher
Informa Healthcare
external identifiers
  • pmid:39673538
  • scopus:85212074469
ISSN
1502-7686
DOI
10.1080/00365513.2024.2439398
language
English
LU publication?
yes
id
516c5e8c-0777-47f9-93e6-f114cf2a0961
date added to LUP
2024-12-16 06:27:49
date last changed
2025-07-15 00:41:17
@article{516c5e8c-0777-47f9-93e6-f114cf2a0961,
  abstract     = {{<p>Direct oral anticoagulants (DOAC) are increasingly common, with bleeding events associated with elevated plasma concentrations. Rotational thromboelastometry (ROTEM), a point-of-care tool for assessing secondary hemostasis, has demonstrated a correlation with increasing concentrations of DOAC. However, previous studies have only partially explored this relationship. The primary aim in the current study was to investigate the impact of increasing rivaroxaban concentrations on clotting time (CT) in the EXTEM assay. The secondary aims were to investigate the impact of increasing rivaroxaban concentrations on clot formation time (CFT) and α-angle (AA) and to investigate the impact of increasing concentrations of dabigatran and apixaban on CT, CFT and AA. Blood from 12 healthy volunteers was spiked to anticipated concentrations of rivaroxaban, dabigatran and apixaban at 0, 50, 100, 200, 500 and 1000 µg/L each. Blood with these varying concentrations was analyzed in four different ROTEM assays and CT, CFT and AA were extracted. CT increased linearly with increasing concentrations of all three DOACs. Rivaroxaban and dabigatran spiked blood showed an increase in CT-EXTEM for the 200–1000µg/L concentrations, compared to baseline, and apixaban for the 500–1000 µg/L concentrations. CFT and AA were affected only in supratherapeutic concentrations for all tested DOACs and primarily in the INTEM assay. Among the tested DOACs, apixaban demonstrated the least impact on CT across all assays. In conclusion, ROTEM-derived CT measurements can serve as surrogate markers for DOAC concentrations.</p>}},
  author       = {{Sunnersjö, Lotta and Lindquist, Lukas and Schött, Ulf and Hillarp, Andreas and Undén, Johan and Kander, Thomas}},
  issn         = {{1502-7686}},
  keywords     = {{anticoagulants; apixaban; dabigatran; Dose–response relationship; hemostasis; rivaroxaban; thromboelastometry}},
  language     = {{eng}},
  number       = {{7-8}},
  pages        = {{540--546}},
  publisher    = {{Informa Healthcare}},
  series       = {{Scandinavian Journal of Clinical and Laboratory Investigation}},
  title        = {{Impact of direct oral anticoagulants on ROTEM® variables; a sample size-calculated experimental study}},
  url          = {{http://dx.doi.org/10.1080/00365513.2024.2439398}},
  doi          = {{10.1080/00365513.2024.2439398}},
  volume       = {{84}},
  year         = {{2024}},
}