Unusual zymogen activation patterns in the protein corona of Ca-zeolites

Zymogen (prothrombin) activation is central to the process of haemostasis (blood clotting) in the body, preventing serious blood loss and death from haemorrhagic shock. Zeolites comprise a family of crystalline microporous aluminosilicates that show increasing promise for use in massive bleeding control. However, the mechanism of zeolite-initiated haemostasis has remained unclear. Here, we investigate zeolite-initiated thrombin activation at the molecular level, and show that a prothrombinase complex can assemble on the inorganic surface of calcium-ion-exchanged zeolites (Ca-zeolites). Compared to natural platelet-based physiological processes, prothrombin-to-thrombin conversion on the surface of Ca-zeolite displays a striking thrombin activation pattern, with an exceptionally high plateau thrombin activity and at least 12-fold enhanced endogenous thrombin. The results provide a mechanistic understanding of how the zeolite surface functionally contributes to thrombin activation, paving the way towards the design of improved agents for bleeding management. Zeolites are promising materials to prevent serious blood loss and death from haemorrhagic shocks, but their mode of action to initiate blood clotting remained vague. Now, this is investigated at the molecular level, revealing the formation of a prothrombinase complex on the surface of Ca-zeolites.