Surface-attached amphipathic peptides reduce hemorrhage in vivo

Abstract

The leading causes of death for trauma patients in civilian and combat settings are traumatic brain injury and uncontrolled hemorrhage, respectively. This study examines the hemostatic activity of an ideal amphipathic peptide (IAP) attached to a biocompatible surface. Procoagulant properties of IAP attached to a surface were first tested, in vitro, using factor Xa and thrombin generation assays and thromboelastography. Rabbits and swine were used for in vivo studies. Injuries were performed using scalpel blade 11, and free bleeding was allowed for five seconds. While bleeding, IAP coupled to a hydrogel or QuikClot were applied to the wound and the time was recorded until bleeding stopped. Results show that when IAP is attached to a surface, both factor IXa and factor Xa activities are promoted. Thromboelastography shows that surface-attached IAP results in earlier onset and stronger clot formation. In rabbits, the incorporation of IAP onto a biocompatible hydrogel reduces bleeding times by 40% (p < 0.03). In pigs, bleeding times are reduced 30% to 50% (p < 0.02) by surface-coupled IAP. Finally, using a rabbit liver laceration model, the properties of surface-coupled IAP are less damaging when compared with QuikClot, a currently used material in external hemorrhagic injuries. This study provides a relevant proof of concept for the development of IAP coupled to a biocompatible surface as a hemostatic agent, that is potentially safer than the commercially available QuikClot.