Comparison of a New Hemostatic Agent to Current Combat Hemostatic Agents in a Swine Model of Lethal Extremity Arterial Hemorrhage

Biomedical Engineering, Virginia Commonwealth University, Ричмонд, Virginia, United States
The Journal of trauma (Impact Factor: 2.96). 08/2007; 63(2):276-83; discussion 283-4. DOI: 10.1097/TA.0b013e3180eea8a5
Source: PubMed


Gaining hemostatic control of lethal vascular injuries sustained in combat using topical agents remains a challenge. Recent animal testing using a lethal arterial injury model has demonstrated that QuikClot zeolite granules (QCG) and the HemCon chitosan bandage (HC) are not capable of providing hemostasis and improving survival over the Army gauze field bandage (AFB). We have developed a new hemostatic agent consisting of a granular combination of a smectite mineral and a polymer (WoundStat) capable of producing hemostasis in the face of high-pressure arterial bleeding. We compared the performance of WoundStat (WS) to QCG, HC, AFB, and the new QuikClot zeolite Advance Clotting Sponge (ACS) in a lethal vascular injury model.
Hemostatic agents were tested using a lethal femoral artery vascular injury model. Twenty-five (5 per group) male swine (42 kg +/- 3 kg) were anesthetized, instrumented, and splenectomized. A lethal femoral artery injury was produced by creating a 6-mm arteriotomy in the vessel. After 45 seconds of hemorrhage, animals were randomized to be treated with AFB (control group), HC, QCG, ACS, or WS. Pressure (200 mm Hg) was applied over the product in the wound for 3 minutes. A second application and 3 additional minutes of pressure was provided if hemostasis was not achieved. Fluid resuscitation was begun at the time of application with 500 mL of Hextend, followed by lactated Ringer's solution at 100 mL/min to achieve and maintain a postapplication mean arterial blood pressure of 65 mm Hg. Animals were observed for 180 minutes or until death. Primary endpoints were survival, survival time, post-treatment blood loss, and amount of resuscitation fluid.
All animals treated with WS survived to 180 minutes and required only a single application. No animal in the AFB, QCG, or ACS group survived. One animal in the HC group survived. Survival (p < 0.05) and survival times (p < 0.0001) for WS animals were significantly greater than for all other groups. No significant difference in survival or survival time existed between the AFB, QCG, ACS, or HC groups. Post-treatment blood loss (p = 0.0099) and postresuscitation fluid volume (p = 0.006) was significantly less for animals treated with WS than for all other groups. No significant difference in these parameters existed between the AFB, QCG, ACS, and HC groups.
WS was superior to the other hemostatic agents tested in this study of lethal arterial vascular injury. Additional study is warranted on this agent to determine its potential for use in combat and civilian trauma.

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    • "Furthermore, significant blood loss predisposes individuals to hypothermia, coagulopathy, infection , acidosis and multiple organ failure. Therefore, early control of hemorrhage is essential for initial survival and also for optimal recovery [8]. The US military's Committee on Tactical Combat Casualty Care (CTCCC) is the group responsible for developing guidelines for the management of wounded military personnel. "
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    ABSTRACT: Hemorrhage is the leading cause of death from trauma. Intravenous (IV) fluid resuscitation in these patients may cause hemodilution and secondary hemorrhage. In addition, hypothermia may interfere with coagulation. The purposes of this study were to compare the effectiveness QuikClot Combat Gauze (QCG) to a control group on hemorrhage in a hemodiluted, hypothermic model, and to determine the effects of IV volume resuscitation on rebleeding. This was a prospective, between subjects, experimental design. Yorkshire swine were randomly assigned to two groups: QCG (n = 13) or control (n = 13). The subjects were anesthetized. Hypothermia (temperature of ≤34.0 °C) was induced; 30% of their blood volume was exsanguinated. A 3:1 replacement of Lactated Ringer's was administered to dilute the remaining blood. The femoral artery and vein were transected. After 1 min of uncontrolled hemorrhage, QCG was placed into the wound followed by standard wound packing. The control group underwent the same procedures without QCG. After 5 min of manual pressure, a pressure dressing was applied. Following 30 min, the dressings were removed, and blood loss was calculated. For subjects achieving hemostasis, up to 5 L of IV fluid was administered or until bleeding occurred, which was defined as >2% total blood volume. The QCG had significantly less hemorrhage than the control (QCG = 30 ± 99 mL; control = 404 ± 406 mL) (p = .004). Further, the QCG group was able to tolerate more resuscitation fluid before hemorrhage (QCG = 4615 ± 1386 mL; control = 846 ± 1836) (p = .000).
    Annals of Medicine and Surgery 06/2014; 3(2):21–25. DOI:10.1016/j.amsu.2014.03.001
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    • "Preventing severe hemorrhage is essential for reducing mortality and improving survival in emergencies or other medical events, such as severe trauma.1,2 Hemostatic biomaterials reduce or stop bleeding by accelerating blood clot formation, and they must be biocompatible and must have low toxicity. "
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    ABSTRACT: Chitosan nanoparticles (NPs) decorated with adenosine diphosphate (ADP) (ANPs) or fibrinogen (FNPs) were used to fabricate hemostatic NPs that can shorten blood clotting time and prevent severe local hemorrhage. The structure and mechanical properties of the blood clot induced with ANP (clot/ANP) or FNP (clot/FNP) were also investigated. The NPs, ANPs, and FNPs, which had particle sizes of 245.1±14.0, 251.0±9.8, and 326.5±14.5 nm and zeta potentials of 24.1±0.5, 20.6±1.9, and 15.3±1.5 mV (n=4), respectively, were fabricated by ionic gelation and then decorated with ADP and fibrinogen. The zeta potentials and Fourier transform infrared (FTIR) spectroscopy of the NPs confirmed that their surfaces were successfully coated with ADP and fibrinogen. The scanning electron microscope (SEM) micrographs of the structure of the clot induced with "undecorated" chitosan NPs (clot/NP), clot/ANP, and clot/FNP (at 0.05 wt%) were different, after citrated bloods had been recalcified by a calcium chloride solution containing NPs, ANPs, or FNPs. This indicated that many NPs adhered on the membrane surfaces of red blood cells, that ANPs induced many platelet aggregates, and that FNPs were incorporated into the fibrin network in the clots. Measurements of the blood clotting times (Tc) of blood clot/NPs, clot/ANPs, and clot/FNPs, based on 90% of ultimate frequency shifts measured on a quartz crystal microbalance (QCM), were significantly (P<0.05) (n=4) shorter than that of a clot induced by a phosphate-buffered solution (PBS) (clot/PBS) (63.6%±3.1%, 48.3%±6.2%, and 63.2%±4.7%, respectively). The ΔF2 values in the spectra of frequency shifts associated with the propagation of fibrin networks in the clot/ANPs and clot/FNPs were significantly lower than those of clot/PBS. Interestingly, texture profile analysis of the compressional properties showed significantly lower hardness and compressibility in clot/NPs and clot/ANPs (P<0.05 or better) (n=4) compared with clot/PBS and clot/FNPs. Accordingly, among the hemostatic NPs, ANP substantially reduced blood clotting times, ΔF2 values, and compression flow properties of the clot. Hence, ANPs have potential applications for preventing severe local hemorrhage.
    International Journal of Nanomedicine 03/2014; 9(1):1655-64. DOI:10.2147/IJN.S57855 · 4.38 Impact Factor
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    • "In one study it was shown that horse collagen has positive effects in bleeding control in patients undergoing simple elective operations(11). These agents also showed various side effects in many previous studies (12). The US Army Institute for Surgical Research described the ideal qualities of hemostatic agents for pre-hospital and combat use (13) These characteristic features are: 1- Capability to stop large vessel arterial and venous bleeding within 2 minutes of application. "
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    ABSTRACT: In modern life, the incidence of traumatic injuries increases daily. In accidents which lead to trauma, massive bleeding is the main cause of death. Nowadays, many different chemical and herbal agents are available for quick control of bleeding. In this study, we compare the effectiveness of two different types of chemical agents for control of bleeding in an animal model. This research was done comparing two hemostaticagents- "Chitohem" and "Quikclot". Ten healthy IR Iranian sheep were chosen and were blindly divided into two different groups. In each of the groups, one of the aforementioned agents was to be applied. First, four main limb arteries of the sheep were dissected linearly and after measuring the volume of bleeding in the first 60 seconds, the chemical agent was applied to the site of bleeding. After that, the duration of bleeding, the volume of bleeding and the secondary blood pressure were measured and compared. There were no significant differences between the primary features of the animals in two groups (Weight, Baseline Systolic Blood Pressure and Pre-treatment Blood loss). In dependent quantities such as the volume of bleeding after the usage of chemical agents, secondary systolic blood pressure, the results were in favor of "Quick Clot" (P < 0.001 for volume of bleeding, P = 0.008 for secondary blood pressures and P < 0.001 for the necessary time for the bleeding to stop). In this study, it seems that activity of "Quikclot" in cessation of bleeding of large arterial vessels was slightly better than "Chitohem". Due to limitations which we had in this study, further studies are necessary to show the actual differences between these agents and their side effects.
    Trauma Monthly 12/2012; 16(4):188-90. DOI:10.5812/kowsar.22517464.2850
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