Antithrombotic and prohemorrhagic actions of different concentrations of apixaban in patients exposed to single and dual antiplatelet regimens
Abstract We evaluated modifications in the hemostatic balance of different concentrations of apixaban (APIX) in 25 healthy donors and 53 patients treated with aspirin (ASA, n = 21), ASA and clopidogrel (ASA + CLOPI, n = 11), or ASA and ticagrelor (ASA + TICA, n = 21). Blood samples from participants...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-12-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-50347-2 |
| _version_ | 1797371136255721472 |
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| author | Julia Martinez-Sanchez Leticia Castrillo Didac Jerez Sergi Torramade-Moix Marta Palomo Guiomar Mendieta M. Urooj Zafar Ana Belén Moreno-Castaño Pablo Sanchez Juan Jose Badimon Maribel Diaz-Ricart Gines Escolar Mercè Roqué |
| author_facet | Julia Martinez-Sanchez Leticia Castrillo Didac Jerez Sergi Torramade-Moix Marta Palomo Guiomar Mendieta M. Urooj Zafar Ana Belén Moreno-Castaño Pablo Sanchez Juan Jose Badimon Maribel Diaz-Ricart Gines Escolar Mercè Roqué |
| author_sort | Julia Martinez-Sanchez |
| collection | DOAJ |
| description | Abstract We evaluated modifications in the hemostatic balance of different concentrations of apixaban (APIX) in 25 healthy donors and 53 patients treated with aspirin (ASA, n = 21), ASA and clopidogrel (ASA + CLOPI, n = 11), or ASA and ticagrelor (ASA + TICA, n = 21). Blood samples from participants were spiked ex vivo with apixaban 0 (APIX0), 40 (APIX40), and 160 ng/mL (APIX160). We assessed the effects of APIX on (1) clot formation, by ROTEM thromboelastometry; (2) thrombin generation primed by platelets; and (3) platelet and fibrin interactions with a thrombogenic surface, in a microfluidic model with circulating blood. APIX caused dose-related prolongations of clotting time with minimal impact on other ROTEM parameters. Thrombin generation was significantly inhibited by APIX160, with ASA + TICA actions showing the strongest inhibition (p < 0.01 vs APIX0). Microfluidic studies showed that APIX160 was more potent at suppressing platelet and fibrin interactions (p < 0.001 vs. APIX0). APIX40 demonstrated a consistent antithrombotic action but with a favorable protective effect on the structural quality of fibrin. APIX potentiated the antithrombotic effects of current antiplatelet regimens. APIX at 40 ng/mL, enhanced the antithrombotic action of single or dual antiplatelet regimens but was more conservative for hemostasis than the 160 ng/mL concentration. |
| first_indexed | 2024-03-08T18:15:25Z |
| format | Article |
| id | doaj.art-478cdc8469be40b48d3211ca7539f3b4 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-08T18:15:25Z |
| publishDate | 2023-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-478cdc8469be40b48d3211ca7539f3b42023-12-31T12:10:17ZengNature PortfolioScientific Reports2045-23222023-12-0113111210.1038/s41598-023-50347-2Antithrombotic and prohemorrhagic actions of different concentrations of apixaban in patients exposed to single and dual antiplatelet regimensJulia Martinez-Sanchez0Leticia Castrillo1Didac Jerez2Sergi Torramade-Moix3Marta Palomo4Guiomar Mendieta5M. Urooj Zafar6Ana Belén Moreno-Castaño7Pablo Sanchez8Juan Jose Badimon9Maribel Diaz-Ricart10Gines Escolar11Mercè Roqué12Hemostasis and Erythropathology LaboratoryHematopathologyDepartment of Pathology, Centre de Diagnostic Biomedic (CDB), Hospital Clinic de Barcelona, Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Universitat de BarcelonaDepartment of Cardiology, ICCV, Hospital Clinic de Barcelona, IDIBAPS, Universitat de BarcelonaHemostasis and Erythropathology LaboratoryHematopathologyDepartment of Pathology, Centre de Diagnostic Biomedic (CDB), Hospital Clinic de Barcelona, Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Universitat de BarcelonaHemostasis and Erythropathology LaboratoryHematopathologyDepartment of Pathology, Centre de Diagnostic Biomedic (CDB), Hospital Clinic de Barcelona, Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Universitat de BarcelonaHemostasis and Erythropathology LaboratoryHematopathologyDepartment of Pathology, Centre de Diagnostic Biomedic (CDB), Hospital Clinic de Barcelona, Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Universitat de BarcelonaDepartment of Cardiology, ICCV, Hospital Clinic de Barcelona, IDIBAPS, Universitat de BarcelonaDepartment of Medicine, AtheroThrombosis Research Unit (ATRU), Cardiovascular Institute, Icahn School of Medicine at Mount SinaiHemostasis and Erythropathology LaboratoryHematopathologyDepartment of Pathology, Centre de Diagnostic Biomedic (CDB), Hospital Clinic de Barcelona, Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Universitat de BarcelonaDepartment of Marine Biology and Oceanography, Institut de Ciències del Mar, Spanish National Research CouncilDepartment of Medicine, AtheroThrombosis Research Unit (ATRU), Cardiovascular Institute, Icahn School of Medicine at Mount SinaiHemostasis and Erythropathology LaboratoryHematopathologyDepartment of Pathology, Centre de Diagnostic Biomedic (CDB), Hospital Clinic de Barcelona, Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Universitat de BarcelonaHemostasis and Erythropathology LaboratoryHematopathologyDepartment of Pathology, Centre de Diagnostic Biomedic (CDB), Hospital Clinic de Barcelona, Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Universitat de BarcelonaDepartment of Cardiology, ICCV, Hospital Clinic de Barcelona, IDIBAPS, Universitat de BarcelonaAbstract We evaluated modifications in the hemostatic balance of different concentrations of apixaban (APIX) in 25 healthy donors and 53 patients treated with aspirin (ASA, n = 21), ASA and clopidogrel (ASA + CLOPI, n = 11), or ASA and ticagrelor (ASA + TICA, n = 21). Blood samples from participants were spiked ex vivo with apixaban 0 (APIX0), 40 (APIX40), and 160 ng/mL (APIX160). We assessed the effects of APIX on (1) clot formation, by ROTEM thromboelastometry; (2) thrombin generation primed by platelets; and (3) platelet and fibrin interactions with a thrombogenic surface, in a microfluidic model with circulating blood. APIX caused dose-related prolongations of clotting time with minimal impact on other ROTEM parameters. Thrombin generation was significantly inhibited by APIX160, with ASA + TICA actions showing the strongest inhibition (p < 0.01 vs APIX0). Microfluidic studies showed that APIX160 was more potent at suppressing platelet and fibrin interactions (p < 0.001 vs. APIX0). APIX40 demonstrated a consistent antithrombotic action but with a favorable protective effect on the structural quality of fibrin. APIX potentiated the antithrombotic effects of current antiplatelet regimens. APIX at 40 ng/mL, enhanced the antithrombotic action of single or dual antiplatelet regimens but was more conservative for hemostasis than the 160 ng/mL concentration.https://doi.org/10.1038/s41598-023-50347-2 |
| spellingShingle | Julia Martinez-Sanchez Leticia Castrillo Didac Jerez Sergi Torramade-Moix Marta Palomo Guiomar Mendieta M. Urooj Zafar Ana Belén Moreno-Castaño Pablo Sanchez Juan Jose Badimon Maribel Diaz-Ricart Gines Escolar Mercè Roqué Antithrombotic and prohemorrhagic actions of different concentrations of apixaban in patients exposed to single and dual antiplatelet regimens Scientific Reports |
| title | Antithrombotic and prohemorrhagic actions of different concentrations of apixaban in patients exposed to single and dual antiplatelet regimens |
| title_full | Antithrombotic and prohemorrhagic actions of different concentrations of apixaban in patients exposed to single and dual antiplatelet regimens |
| title_fullStr | Antithrombotic and prohemorrhagic actions of different concentrations of apixaban in patients exposed to single and dual antiplatelet regimens |
| title_full_unstemmed | Antithrombotic and prohemorrhagic actions of different concentrations of apixaban in patients exposed to single and dual antiplatelet regimens |
| title_short | Antithrombotic and prohemorrhagic actions of different concentrations of apixaban in patients exposed to single and dual antiplatelet regimens |
| title_sort | antithrombotic and prohemorrhagic actions of different concentrations of apixaban in patients exposed to single and dual antiplatelet regimens |
| url | https://doi.org/10.1038/s41598-023-50347-2 |
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