Hemostatic Properties of Topically Applied Q8009 a Snake Venom Protease

Abstract

Previous in vitro work characterized the protease Q8009 from the venom of the Australian brown snake Pseudonaja textilis textilis with hemostatic properties and Factor Xa-like activity. In vivo studies reported herein indicate that Q8009 mixed with collagen matrix and applied to surgical injury sites is superior to thrombin in blood loss reduction and a shorter time-to-hemostasis. The dermal injury model involved a dermal incision (1 mm deep x 5 mm in length) on each hind limb manus between digits 2 and 3. The tail-tip model utilized transection of the last 2 mm of the tail-tip. Blood was collected for 12 one-minute intervals or until hemostasis, and blood loss was measured by quantifying hematin concentration. In the dermal injury model, Q8009 at concentrations of 100 [mu]g/mL, 250 [mu]g/mL and 1,000 [mu]g/mL significantly reduced (p<0.001) blood loss, compared to thrombin and reduced the time-to-hemostasis to ~ 2.0 minutes compared to 4.77 minutes with thrombin. In the tail-tip transection model, Q8009 and collagen matrix did not significantly reduce blood loss relative to thrombin. However, Q8009 (1,000 [mu]g/mL) without collagen matrix, significantly reduced (p<0.001) blood loss from the tail wound. When the Tail-Tip and Dermal models were averaged together, thrombin reduced overall blood loss by 72%, Q8009 at 100 [mu]g/mL, 250 [mu]g/mL and 1,000 [mu]g/mL reduced blood loss by 75%, 90% and 83%, respectively. Therefore, topical application of Q8009 significantly reduced total blood loss and shortened the time-to-hemostasis, when compared to thrombin. This work was supported by QRxPharma.