A cysteine enzyme hemostat for efficient heparin-tolerant blood coagulation

It is challenging to stop bleeding effectively in patients treated with heparin which leads to enhanced risk of uncontrolled bleeding during operation. Herein, we report an easy-to-use and heparin-tolerant hemostatic agent based on a thrombin-like cysteine enzyme (papain), which catalyzes the hydrolysis of fibrinogen and cross-linking of fibrin clots. A papain-based hemostat with increased procoagulant activity is developed through immobilizing papain on the cellulose carrier, which displays short clotting time in both normal and heparinized plasmas. The excellent hemostatic performance of the papain-based hemostat is further confirmed with reduced hemostatic time and limited blood loss in a mouse tail amputation model, rabbit auricular artery injury model and rat liver injury model, in which a natural coagulation system fails to function on account of heparin. This bio-hemostat has great potential to reverse the effect of heparin and stop topical hemorrhage rapidly in surgical procedures.

Automated summary

We report an easy-to-use and heparin-tolerant hemostatic agent based on a thrombin-like cysteine enzyme (papain), which effectively stops bleeding by catalyzing the hydrolysis of fibrinogen and cross-linking of fibrin clots. The hemostatic agent, immobilized on a cellulose carrier, displays short clotting time in both normal and heparinized plasmas. It shows excellent hemostatic performance in various animal models where the natural coagulation system fails to function due to heparin, indicating its great potential as a bio-hemostat to rapidly stop bleeding in surgical procedures.