Sökning: WFRF:(Nylander K)
> (2015-2019) >
Hemostatic effects ...
Hemostatic effects of the ticagrelor antidote MEDI2452 in pigs treated with ticagrelor on a background of aspirin
-
- Pehrsson, S. (författare)
- AstraZeneca AB
-
- Johansson, K. J. (författare)
- AstraZeneca AB
-
- Janefeldt, A. (författare)
- AstraZeneca AB
-
visa fler...
-
- Sandinge, A. S. (författare)
- AstraZeneca AB
-
Maqbool, S. (författare)
-
Goodman, J. (författare)
-
- Sanchez, J. (författare)
- AstraZeneca AB
-
- Almqvist, Joachim E, 1980 (författare)
- Chalmers tekniska högskola,Chalmers University of Technology
-
- Gennemark, Peter, 1974 (författare)
- AstraZeneca AB
-
- Nylander, S. (författare)
- AstraZeneca AB
-
visa färre...
-
(creator_code:org_t)
- Elsevier BV, 2017
- 2017
- Engelska.
-
Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7836 .- 1538-7933. ; 15:6, s. 1213-1222
- Relaterad länk:
-
http://dx.doi.org/10...
-
visa fler...
-
https://onlinelibrar...
-
https://research.cha...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- Background: Ticagrelor, a P2Y12 antagonist, is approved for the prevention of thromboembolic events. However, antiplatelet therapies carry a risk of bleeding. Objective: To explore the hemostatic effects of MEDI2452, an antidote for ticagrelor. Methods: Pigs, pretreated with aspirin, were given an intravenous infusion of ticagrelor or vehicle. At the end of the infusion, a piece of a liver lobe was cut off and a bolus of MEDI2452 or vehicle was administered intravenously. Blood was collected to monitor blood loss, mean arterial blood pressure (MAP) was recorded and survival time was observed over 4 h. Blood samples for drug plasma exposures and platelet aggregation were collected. Results: MEDI2452 eliminated the free concentrations of ticagrelor and its active metabolite AR-C124910XX within 5 min. ADP-induced platelet aggregation was close to normal at 60 min, which was not significantly different from aspirin alone. MEDI2452 numerically reduced ticagrelor-mediated effects: bodyweight- adjusted blood loss in the 15-to 90-min interval, 12 (confidence interval [ CI] 95% 7-28] vs. 17 (CI 95% 5-31) (ticagrelor and aspirin) vs. 5 (CI 95% 3-9) mL kg(-1) (aspirin alone), survival 70% (CI 95% 47-100) vs. 45% (CI 95% 21-92) (ticagrelor and aspirin) vs. 100% (CI 95% 100-100) (aspirin alone), and median survival time, 240 (CI 95% 180-240) vs. 169 (CI 95% 64-240) (ticagrelor and aspirin) vs. 240 (CI 95% 240-240) min (aspirin alone). Finally, MEDI2452 significantly attenuated the decline in MAP, 0.08 (CI 95% 0.07-0.09) vs. 0.141 (CI 95% 0.1350.148) (ticagrelor and aspirin) vs. 0.04 (CI 95% 0.030.05) mmHg per min (aspirin alone) and maintained MAP at a significantly higher level, 73 (CI 95% 51-95) vs. 48 (CI 95% 25-70) (ticagrelor and aspirin) vs. 115 (CI 95% 94136) mmHg (aspirin alone). Conclusion: MEDI2452 eliminated free ticagrelor and AR-C124910XX within 5 min. This translated into a gradual normalization of ADPinduced platelet aggregation and significant improvement in blood pressure and numerical but non-significant improvements in blood-loss and survival.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Anestesi och intensivvård (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Anesthesiology and Intensive Care (hsv//eng)
Nyckelord
- swine
- antidote
- hemorrhage
- ticagrelor
- blood platelets
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
-
Pehrsson, S.
-
Johansson, K. J.
-
Janefeldt, A.
-
Sandinge, A. S.
-
Maqbool, S.
-
Goodman, J.
-
visa fler...
-
Sanchez, J.
-
Almqvist, Joachi ...
-
Gennemark, Peter ...
-
Nylander, S.
-
visa färre...
- Om ämnet
-
- MEDICIN OCH HÄLSOVETENSKAP
-
MEDICIN OCH HÄLS ...
-
och Klinisk medicin
-
och Anestesi och int ...
- Artiklar i publikationen
-
Journal of Throm ...
- Av lärosätet
-
Chalmers tekniska högskola