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Significance: Approximately 35% of hemorrhagic deaths occur before hospital arrival, with the risk amplified by anticoagulant therapies. To address this, our research introduces a next-generation chitosan hemostat, rationally designed with optimized pore size and connectivity. This design allows the hemostat to quickly absorb blood and concentrate clotting components, effectively counteracting anticoagulant effects. Contrary to previous beliefs that chitosan does not participate in the physiological clotting process, we identified its direct role in activating platelets via the TLR-2 (Toll-like receptor 2), thereby initiating the coagulation cascade in the presence of currently approved anticoagulants. This study presents an approach in hemostat development for emergency care, especially valuable for patients on anticoagulants.