Carboxymethyl cellulose granules (CMC-G) and kappa-carrageenan/polyethylene oxide/polyethylene glycol dressing (KPP-D) hemostatic agents, developed through radiation-induced crosslinking and sterilization, were tested in Sprague-Dawley rats using three bleeding models: (a) deep wound with the puncture of femoral artery; (b) aortic puncture; and (c) partial nephrectomy. Dressing and granules were applied in the animals without sustained compression and monitored for a period of 7 or 14 days. Comparisons were made against the commercial chitosan-based agent, Celox (CLX). Primary outcomes observed were bleeding time, the incidence of re-bleeding, animal survival, as well as gross and microscopic changes. The KPP-D group showed the shortest bleeding time for all bleeding models (a. 2.75 ± 0.64, b. 1.63 ± 0.54, c. 2.05 ± 0.62), significantly faster than all the other treatment groups. KPP-D also registered the highest survival rate of 100% with no display of gross abnormalities. CMC-G showed comparable bleeding time with CLX products but had a better survival rate at 98% compared to 96%. The incidence of re-bleeding was greater in CLX treated groups as well as more occurrence of granular adhesions that impacted mortality outcomes. Findings indicate the efficacy of KPP-D in the treatment of severe hemorrhage due to traumatic injury and intraoperative cases, while CMC-G was more suited for external trauma. Complications arising from inflammation, granules deposition, and adhesions emphasize stringent handling and removal of granular hemostat as a critical consideration in hemostat development and testing.
Keywords: Hemostatic agents; bleeding animal model; efficacy; granules; hydrogel dressing.