Thrombin production and human neutrophil elastase sequestration by modified cellulose dressings and their electrokinetic analysis

Authors: Edwards, Judson - Vince; Prevost, Nicolette

Submitted to: Biomedical Materials Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/7/2011
Publication Date: 12/15/2011
Citation: Edwards, J.V., Prevost, N.T. 2011. Thrombin production and human neutrophil elastase sequestration by modified cellulose dressings and their electrokinetic analysis. Journal of Functional Biomaterials. 2(4):391-413.

Interpretive Summary: The development of improved battlefield dressings has become a priority. Half of all deaths on the battlefield are caused by uncontrolled hemorrhage. In addition, high blood loss can lead to hypothermia, multiple organ failure and infection. Thus, rapid hemostasis is essential for survival and recovery. The development of improved hemostatic agents for use in lethal extremity arterial hemorrhages has increased over recent years. The U.S. Army Institute for Surgical Research (USISR) and the Uniformed Services University of the Health Sciences has outlined ideal properties needed in a battlefield dressing. These include the following: 1) being able to rapidly stop large vessel arterial and venous bleeding 2 minutes after application when applied to an actively bleeding wound through a pool of blood. 2) no requirement for mixing or pre-application preparation; 3) simplicity of application by wounded victim, buddy, or medic; 4) light weight and durable; 5) long shelf life in extreme environments; 6) safe to use with no risk of injury to tissues or transmission of infection; and 7) inexpensive. With this list of ideal properties the question arises: Is there any deployed product capable of stopping or reducing groin arterial bleeding and preventing exsanguinations that otherwise could not be controlled by the standard gauze dressing? This paper outlines an approach to the use of cotton and bentonite as a hemorrhage control dressing, and it studies the clotting properties of both substances as is related to thrombin production in whole blood clotting. Aminized cotton was found to boost thrombin production and accelerate clotting. The findings of the study suggest a synergistic effect between aminized cotton and bentonite to rapidly seal arterial hemorrhages and promote clotting. The benefits of this type of product to the consumer have potential life saving implications when applied to battlefield use and civilian trauma.

Technical Abstract: Hemostatic control of lethal extremity arterial hemorrhage has been addressed with a variety of dressing motifs which have included the use of widely divergent materials i.e. clay minerals, fibrin sealant, and chitosan. The rapid deployment of some of these products as combat dressings reflects the improvement in hemostatic control performance over the standard army cotton gauze field dressing. Recently, Ward et al. (J Trauma, 2007; 63;276-284) reported a granular combination of a smectite mineral and a polymer (WoundStat) which was superior to other hemorrhage control agents when tested in a swine model study of lethal arterial vascular injury. We report here a structural composite which contains a combination of WoundStat and aminized cotton prepared as a prototype (BAC), which after a single application to the lethal femoral arteriotomy resulted in animal survival. The coagulation properties of BAC were assessed by monitoring the rate of thrombin production with a fluorogenic substrate using plasma and whole blood analysis. The rate of thrombin production in the presence of the hemostatic materials that comprised the dressing was monitored with a fluorogenic peptide substrate. The effect of the materials activation of thrombin generation was also monitored by measuring actual thrombin produced in plasma with known activation agents including micelles, tissure factor and calcium chloride. Streaming zeta potential measurements performed on the materials used in BAC demonstrated an increase in zeta potential which correlates with increased hemostatic performance, and the relative swelling and moisture content properties. The presence of aminized cotton was shown to potentiate increased thrombin production and accelerated coagulation.