Hirudin-Like Noninvasive Polyurethane Solid Anticoagulant Fabricated by One-Pot In Situ Solution Polymerization and Phase Conversion Methods

In the process of blood purification, the use of anticoagulants is necessary to prevent treatment interruptions due to blood clotting. Currently, traditional liquid anticoagulant medications, which enter the bloodstream, may lead to safety concerns, such as internal bleeding and thrombocytopenia. To address these issues, we prepared solid anticoagulant microspheres based on polyurethane (PU) through one-pot in situ solution polymerization and phase conversion methods. The microspheres prolong the activated partial thromboplastin time (APTT) and thrombin time (TT) by 30-40 s and demonstrate good blood compatibility. Interestingly, we find that polyurethane in the microspheres has the ability to selectively bind thrombin, like the anticoagulant mechanism of hirudin. The strong binding between PU and thrombin is confirmed through microscale thermography (MST) (the dissociation constant <i>K</i>_d is about 71 μM). Furthermore, the anticoagulant microspheres, in combination with other studies of anticoagulation mechanisms, are found to inhibit multiple steps in the coagulation cascade. More importantly, the noninvasive microspheres do not release PU into the bloodstream, ensuring the safety of anticoagulation therapy and suggesting significant potential for application in the field of blood purification.