Effect of Apixaban Pretreatment on Alteplase-Induced Thrombolysis: An In Vitro Study

0546625 - BFÚ 2022 RIV CH eng J - Journal Article
Thalerova, S. - Pešková, Michaela - Kittová, Patrícia - Gulati, S. - Víteček, Jan - Kubala, Lukáš - Mikulik, R.
Effect of Apixaban Pretreatment on Alteplase-Induced Thrombolysis: An In Vitro Study.
Frontiers in Pharmacology. Roč. 12, SEP 15 2021 (2021), č. článku 740930. ISSN 1663-9812. E-ISSN 1663-9812
Institutional support: RVO:68081707
Keywords : antagonist oral anticoagulants * acute ischemic-stroke * plasminogen-activator * intravenous thrombolysis * warfarin * clot
OECD category: Pharmacology and pharmacy
Impact factor: 5.988, year: 2021
Method of publishing: Open access
https://www.frontiersin.org/articles/10.3389/fphar.2021.740930/full

Benefit of thrombolytic therapy in patients with acute stroke, who are on anticoagulant treatment, is not well addressed. The aim of this study was to investigate whether apixaban can modify the thrombolytic efficacy of alteplase in vitro. Static and flow models and two variants of red blood cell (RBC) dominant clots, with and without apixaban, were used. Clots were prepared from the blood of healthy human donors and subsequently exposed to alteplase treatment. Apixaban and alteplase were used in clinically relevant concentrations. Clot lysis in the static model was determined both by clot weight and spectrophotometric determination of RBC release. Clot lysis in the flow model was determined by measuring recanalization time, clot length and spectrophotometric determination of RBC release. In the static model, clots without apixaban, compared to those with apixaban had alteplase-induced mass loss 54 +/- 8% vs. 53 +/- 8%, p = 1.00, RBC release 0.14 +/- 0.04 vs. 0.12 +/- 0.04, p = 0.14, respectively. Very similar results were obtained if plasma was used instead of physiological buffered saline as the incubation medium. In the flow model, clot lysis without apixaban, compared to those with apixaban was as follows: recanalization time 107 +/- 46 min vs. 127 +/- 31 min, p = 1.00, recanalization frequency 90 +/- 22% vs. 90 +/- 22%, p = 1.00, clot volume reduction 32 +/- 15% vs. 34 +/- 10%, p = 1.00, RBC release 0.029 +/- 0.007 vs. 0.022 +/- 0.007, p = 0.16, respectively. Apixaban had no positive effect on alteplase-induced thrombolysis in both the in vitro static and flow models. Our data support current clinical practice, such that thrombolysis is contraindicated in stroke treatment for patients who have been treated with anticoagulants./p
Permanent Link: http://hdl.handle.net/11104/0323070