Synergistic effects of rivaroxaban and hypothermia or acidosis on coagulation initiation measured with ROTEM ® : a prospective observational study.
Sunnersjö, Lotta LU ; Ymén, Isak ; Schött, Ulf LU ; Hillarp, Andreas LU ; Undén, Johan LU and Kander, Thomas LU
(2024)
In Thrombosis Journal
22.
p.1-10
- Abstract
BACKGROUND: Hypothermia and acidosis individually inhibit haemostasis. We designed this study with the aim to investigate whether rivaroxaban combined with hypothermia or acidosis exhibit synergistic inhibitory effects on haemostasis using ROTEM ®.
METHODS: Patients with a clinical indication to start rivaroxaban treatment were prospectively included. Blood samples were collected before initiation of treatment and the day after. All blood samples were in vitro modified with respect to temperature (incubated and analysed at 28, 33, 37 and 40 degrees Celsius (°C)) and pH (6.8, 7.0, 7.2 and 7.4). The temperature and acidosis effects on the ROTEM EXTEM variables clotting time (CT), clot formation time (CFT) and alpha-angle (AA) were... (More)
BACKGROUND: Hypothermia and acidosis individually inhibit haemostasis. We designed this study with the aim to investigate whether rivaroxaban combined with hypothermia or acidosis exhibit synergistic inhibitory effects on haemostasis using ROTEM ®.
METHODS: Patients with a clinical indication to start rivaroxaban treatment were prospectively included. Blood samples were collected before initiation of treatment and the day after. All blood samples were in vitro modified with respect to temperature (incubated and analysed at 28, 33, 37 and 40 degrees Celsius (°C)) and pH (6.8, 7.0, 7.2 and 7.4). The temperature and acidosis effects on the ROTEM EXTEM variables clotting time (CT), clot formation time (CFT) and alpha-angle (AA) were measured along with the individual effect of rivaroxaban on the same variables. The additive effect was calculated. The observed (potential synergistic) effects for the temperature and pH modified rivaroxaban samples on the same ROTEM variables, were registered. Differences between the additive and observed (potential synergistic) effects were analysed using matched non-parametric hypothesis testing.
RESULTS: In total, 13 patients were included. Hypothermia and rivaroxaban exhibited a synergistic effect on CT at 28 °C (p = 0.0002) and at 33 °C (p = 0.0007). The same applied for acidosis at pH 6.8 (p = 0.003) and pH 7.0 (p = 0.003). There were no signs of synergistic effects of rivaroxaban and temperature or acidosis on CFT. In AA there were signs of synergism at 28 °C (p = 0,001), but not at other tested temperatures or pH levels.
CONCLUSIONS: The combination rivaroxaban together with hypothermia or acidosis demonstrated inhibitory synergistic effects on haemostasis.
TRIAL REGISTRATION: The study was retrospectively registered 2023-03-01 at ClinTrials.gov with NCT05669313.
(Less)
- author
- Sunnersjö, Lotta
LU
; Ymén, Isak
; Schött, Ulf
LU
; Hillarp, Andreas
LU
; Undén, Johan
LU
and Kander, Thomas
LU
- organization
- publishing date
- 2024-10-18
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Thrombosis Journal
- volume
- 22
- article number
- 91
- pages
- 1 - 10
- publisher
- BioMed Central (BMC)
- external identifiers
-
- pmid:39425155
- ISSN
- 1477-9560
- DOI
- 10.1186/s12959-024-00661-0
- language
- English
- LU publication?
- yes
- additional info
- © 2024. The Author(s).
- id
- 7a960399-d45f-4739-b199-b18fb3af61ce
- date added to LUP
- 2024-10-21 06:30:55
- date last changed
- 2024-10-21 09:52:30
@article{7a960399-d45f-4739-b199-b18fb3af61ce,
abstract = {{<p>BACKGROUND: Hypothermia and acidosis individually inhibit haemostasis. We designed this study with the aim to investigate whether rivaroxaban combined with hypothermia or acidosis exhibit synergistic inhibitory effects on haemostasis using ROTEM ®. </p><p>METHODS: Patients with a clinical indication to start rivaroxaban treatment were prospectively included. Blood samples were collected before initiation of treatment and the day after. All blood samples were in vitro modified with respect to temperature (incubated and analysed at 28, 33, 37 and 40 degrees Celsius (°C)) and pH (6.8, 7.0, 7.2 and 7.4). The temperature and acidosis effects on the ROTEM EXTEM variables clotting time (CT), clot formation time (CFT) and alpha-angle (AA) were measured along with the individual effect of rivaroxaban on the same variables. The additive effect was calculated. The observed (potential synergistic) effects for the temperature and pH modified rivaroxaban samples on the same ROTEM variables, were registered. Differences between the additive and observed (potential synergistic) effects were analysed using matched non-parametric hypothesis testing.</p><p>RESULTS: In total, 13 patients were included. Hypothermia and rivaroxaban exhibited a synergistic effect on CT at 28 °C (p = 0.0002) and at 33 °C (p = 0.0007). The same applied for acidosis at pH 6.8 (p = 0.003) and pH 7.0 (p = 0.003). There were no signs of synergistic effects of rivaroxaban and temperature or acidosis on CFT. In AA there were signs of synergism at 28 °C (p = 0,001), but not at other tested temperatures or pH levels.</p><p>CONCLUSIONS: The combination rivaroxaban together with hypothermia or acidosis demonstrated inhibitory synergistic effects on haemostasis.</p><p>TRIAL REGISTRATION: The study was retrospectively registered 2023-03-01 at ClinTrials.gov with NCT05669313.</p>}},
author = {{Sunnersjö, Lotta and Ymén, Isak and Schött, Ulf and Hillarp, Andreas and Undén, Johan and Kander, Thomas}},
issn = {{1477-9560}},
language = {{eng}},
month = {{10}},
pages = {{1--10}},
publisher = {{BioMed Central (BMC)}},
series = {{Thrombosis Journal}},
title = {{Synergistic effects of rivaroxaban and hypothermia or acidosis on coagulation initiation measured with ROTEM
® : a prospective observational study.}},
url = {{http://dx.doi.org/10.1186/s12959-024-00661-0}},
doi = {{10.1186/s12959-024-00661-0}},
volume = {{22}},
year = {{2024}},
}