AI Article Synopsis
- A significant need exists for anticoagulant therapies that minimize bleeding risk in thrombosis prevention, prompting research into FXIa and FXIIa inhibitors known for their lower bleeding complications.
- This study utilized the SynergyFinder tool to analyze how different proportions of the FXIa inhibitor PN2KPI and FXIIa inhibitor Infestin4 can work together to provide better anticoagulation effects.
- The combination of PN2KPI and Infestin4 in specific doses was shown to effectively prevent blood clotting in mouse models without increasing the risk of bleeding.
Article Abstract
Clinical practice shows that a critical unmet need in the field of thrombosis prevention is the availability of anticoagulant therapy without bleeding risk. Inhibitors against FXIa or FXIIa have been extensively studied because of their low bleeding risk. However, whether these compounds produce synergistic effects has not yet been explored. In this study, analyses of activated partial thromboplastin time in combination with the FXIa inhibitor PN2KPI and the FXIIa inhibitor Infestin4 at different proportions were performed using the SynergyFinder tool identifying synergistic anticoagulation effects. Both an FeCl 3 -induced carotid artery thrombosis mouse model and a transient occlusion of the middle cerebral artery mouse model showed that the combination of PN2KPI and Infestin4, which are 28.57% and 6.25% of the effective dose, respectively, significantly prevents coagulation, and furthermore, dual inhibition does not cause bleeding risk.
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| http://dx.doi.org/10.1097/FJC.0000000000001573 | DOI Listing |
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