Making Sense of the Preclinical Literature on Advanced Hemostatic Products

Abstract

A number of new hemostatic products have been developed recently for use in trauma settings of severe uncontrolled bleeding. Currently, the literature on these products is controversial, with efficacy demonstrated under some circumstances but not others. In this review, we analyze the current literature pertaining to four of the most promising products (dry fibrin sealant dressing, Rapid Deployment Hemostat, HemCon chitosan dressing, and QuikClot) that have been suggested for use in combat casualty care applications. In particular, this analysis takes into account the characteristics of the animal models used for efficacy testing of these products, the desired characteristics of hemostatic dressings, and specific safety considerations. Animal models ranged from those featuring low-pressure/low-flow bleeding to those featuring high-pressure/high-flow bleeding. When data are viewed in the context of the specific characteristics of the differing animal models used, seemingly disparate experimental results related to efficacy and safety become quite complementary and lead to recommendations for the use of different products in different injury scenarios. Mission and training requirements will dictate the use of these products by military and civilian prehospital care providers.

The Effects of BleedArrest, Celox, and TraumaDex on Hemorrhage Control in a Porcine Model

“…Pusateri outlined the ideal qualities of hemostatic agents for civilian and military use. These include (1) being able to rapidly stop large vessel arterial and venous bleeding within 2 min of 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 [36]. This study compared BleedArrest, Celox, and TraumaDex against a standard pressure dressing, the control, in a porcine model of lethal femoral vascular injury.…”

Safety of the long-term application of QuikClot Combat Gauze, ChitoGauze PRO and Celox Gauze in a femoral artery injury model in swine – a preliminary study

“…In response to antifibrinolytic therapy using tranexamic acid, they observed microvascular thrombosis and thromboemboli formation in the portal vein and lung vessels. Microemboli formation was also observed in studies on the effectiveness of zeolite dressings; however, studies on newer generation agents treated with kaolin or chitosan have not revealed their serious side effects (Pusateri et al 2006, Clay et al 2010, Gerlach et al 2010, Kheirabadi et al 2010, Littlejohn et al 2011. In the present study, the coagulopathy and circulatory distress resulted in damage to the lungs, liver, kidneys and heart, which is a sign of the prolonged progressive stage of shock.…”

Hemostatic Efficacy of Local “Chitosan Linear Polymer” Granule in an Experimental Sheep Model with Severe Bleeding of Arteria and Vena Femoralis

“…[1,10,15] The design implemented was unblinded and randomized, with an accepted swine groin injury model (though juvenile sheep were used). The efficacy of 2 treatments for surgically created, lethal, groin arterial and venous bleeding injury were tested.…”

“…[1,6,7] The need for hemostatic agents is greater in the event of large-scale disaster such as terrorist attack, bombing, or devastating earthquake, though in such austere conditions, proper hemostasis of all those wounded is often impossible to achieve. [1][2][3][4][5][8][9][10][11][14][15][16]18,20] The aim of the present study was to test the hemostatic effect of chitosan linear polymer and compression, compared with standard gauze dressing and compression in an experimental young sheep model with severe bleeding of femoral artery and vein. The hypothesis was that chitosan linear polymer would stop the bleeding more quickly and effectively than the standard treatment.…”

“…Rapid hemostasis is essential as a strategy, not only for initial survival, but also for optimal recovery. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] A recent review of autopsies of 982 combat deaths from Iraq and Afghanistan revealed that nearly 24% could have been prevented with effective treatment. Of those potentially preventable deaths, 85% occurred as a result of hemorrhage, 1/3 of which were compressible, 2/3 of which were not, em-…”