Using Topical Hemostatic Agents

By Ellen K. Payne, PhD, ATC, EMT, David C. Berry, PhD, AT, ATC, and S. Robert Seitz, MEd, RN, NRP

This is an extended version of the article "The Use of Topical Hemostatic Agents in Athletic Training," published in the January NATA News. The article is part two of a two-part series. Part one of the series, published in the October 2016 NATA News, reviewed the concepts of hemorrhaging, shock and controlling bleeding as they relate to athletic training and prehospital emergency care.¹ Part one focused on the use of tourniquets in the prehospital setting. Part two of the series will review hemostasis as it relates to the clotting mechanism and provide athletic trainers with evidence regarding the use of topical hemostatic agents in the athletic training setting.

Hemostasis

The body’s physiologic response (hemostasis) to blood loss from trauma involves a complex three-phase process. Coordinated activation of platelets and plasma clotting factors needed to form a platelet-fibrin plug depends on the primary (formation of soft platelet plug) and secondary (stabilization and cross linkage) hemostatic phases. Of central importance in both hemostasic phases is the activation of the clotting cascade, which is broken down into two basic pathways: the intrinsic (activated by collagen, exposed when a blood vessel is damaged) and the extrinsic (activated by tissue damage and the release of tissue factors).

The clotting cascade includes a series of dependent reactions following trauma involving plasma proteins, calcium ions and blood platelets that lead to the conversion of fibrinogen-to-fibrin and an eventual soft platelet plug.² During the initial phase, the muscular wall of a blood vessel contracts to reduce blood flow while creating a turbulent flow of blood. This turbulent flow initiates the second phase of response by attracting platelets that adhere in the presence of collagen to the vessel’s lining, surrounding tissue and each other; further reducing blood flow through the vessel. While the initial clot formed in the vessels greatly decreases blood loss, it is extremely unstable. The third phase of coagulation strengthens the clot through the incorporation of fibrin and red blood cells, resulting in clot expansion and strength.

When bleeding is uncontrollable, numerous topical hemostatic agents are available to affect the biological mechanism of action of the clotting cascade through contact activation and promotion of platelet aggregation.²

Topical Hemostatic Agents

During trauma situations when massive external bleeding can’t be controlled by direct pressure and/or with the use of a tourniquet (ie, hemorrhaging occurring in sites not amenable to tourniquet placement such as the abdomen, groin or chest), the application of topical hemostatic agents are warranted.^3-8 Topical hemostatic agents are commonly used to control severe bleeding, especially in military and, now, civilian prehospital care.^4,7 State emergency medical systems (EMS) are adding various  topical hemostatic agents to ambulance supply lists.⁸

These antihemorrhagic substances produce hemostasis when placed in bleeding wounds by adhering to damaged tissues and sealing the injured blood vessel(s) and/or by accelerating and strengthening the clotting cascade.⁵ The desired characteristics of topical hemostatic agents are presented in Table 1, but currently no “ideal” topical hemostatic agent is being marketed.^9,10 

Table 1. Characteristics of an Ideal Hemostatic Agent

Approved by the FDA

Effective in stopping hemorrhaging

Rapid onset to action (<2 min)

No patient side effects (ie, burns, toxicity, allergic reactions)

No responder side effects or risks

Simple, ready to apply and remove (with no residue) and reapply if necessary

Shelf-life (less than 2 years)

Stable in multiple environmental conditions

Inexpensive

Small, with a low carry weight and easily stored

Biodegradable and bio-absorbable

Should not wash away during rapid bleeding from high-flow vessels

Modified from Pusateri et al,¹⁵ Kheirabadi,⁵ and Stuke¹²

 

Several types of topical hemostatic agents have been developed and marketed for civilian prehospital use. Placed into three classes by mechanism of action and into two forms of delivery hemostatic products lack generic alternatives and vary in delivery method even among the same classes of product, so one company’s product can vary greatly from another(s).^4,10 Commercially available products have undergone multiple stages of development and must be approved by the U.S. Food and Drug Administration before becoming available. Due to continued research and development (ie., military setting), there are currently three generations of agents commercial available.⁸ Table 2 reviews different topical hemostatic agents.

Table 2. Topical Hemostatic Agents

Class	Active Agent	Product Name	Manufacture	Approximate Retail Price
Factor concentrators	Micropourus polysaccharide particles	TraumaDEX	Medafor, Inc., Minneapolis, MN (www.medafor.com)	$20 for 5 gram single application
Mucoadhesive Agents	Chitosan	HemCon Bandages PRO	HemCon Medical Technologies, Portland, OR (www.hemcon.com)	$150 for 4” x 4” dressing
	Chitosan	ChitoGauze PRO	HemCon Medical Technologies, Portland, OR (www.hemcon.com)	$45 for 3” x 4 yard roll
	Chitosan	ChitoFlex PRO	HemCon Medical Technologies, Portland, OR (www.hemcon.com)	$75 for 3” x 9” roll
	Chitosan	Celox Rapid Gauze	MedTrade Products Ltd., Crew, UK (www.medtrade.co.uk)	$40 for 3” x 5’, z-fold
Procoagulants	Kaolinite	QuickClot Combat Gauze	Z-Medica, Wallingford, CT (www.z-medica.com)	$45 for 3” x 4 yard, z-fold
Multi Category	Proprietary algae-derived polymer	Modified Rapid Deployed Hemostat (mRDH)	Marine Polymer Technologies, Inc., Danvers, MA (mrdhbandage.com/)	$500+ for 4” x 4” dressing

Source: Adapted from Granville-Chapman et al.⁴ and Bennett & Littlejohn^8; Prices as of Oct. 4, 2016

 

Hemostatic agents come in two forms: granular powder and embedded/impregnated dressings. These agents use two mechanisms to produce hemostasis: physically adhering to damaged tissues and sealing injured vessels to prevent further blood loss, and accelerating and strengthening the blood clotting present in the wound by incorporating into the developing clot and producing hemostasis. The second mechanism is achieved by two related reactions: rapid absorption of water from blood in the wound, which concentrates all clotting elements on the injured tissues, and chemical reaction(s) activating the intrinsic coagulation pathway and platelets to promote clot formation. These products depend on the intact coagulation function of patients. It should be noted that the majority of hemostatic agents, including those embedded in dressings, facilitate hemostasis through the second mechanism.

The three classes of action for topical hemostatic agents include factor concentrators, mucoadhesive agents and procoagulants. Factor concentrators rapidly absorb water content of blood and concentrate the cellular and protein components of the blood; this promotes clot formation.⁴ TraumaDEX is example of this type of hemostatic agent. It uses microporous polysaccharide hemospheres from potato starch to promote hemostasis by a gelling action to concentrate natural clotting components.¹⁰ This product doesn’t produce an exothermic reaction when used like the original QuikClot product did. While TraumaDEX is considered safe and easy to use, it has not been utilized by U.S. military forces because the product appears more effective with minor to moderate wounds, not the severe wounds seen in combat.¹⁰ This product may have more uses in civilian settings.

Mucoadhesive agents work through a strong adherence to damaged tissues and physically seal bleeding wounds.^12,13 Chitosan-based products, available from multiple manufactures, are examples of this type of agent. These include HemCon Bandage, ChitoGauze and Celox Gauze, to name a few. When the product makes contact with blood, the chitosan swells, gels and sticks together to make a gel-like clot without generating an exothermic reaction.¹⁴ These products work completely independent of body’s clotting system, which is one of the benefits of these agents.⁸ Mucoadhesive agents must have direct pressure applied to the wound after application to allow the product to work properly.    

Procoagulants are the third type of topical hemostatic agents. These function by activating the clotting cascade or delivering high concentrations of procoagulant factors to the bleeding wound.¹⁰ This type includes Combat Gauze, the current first line of treatment for the U.S. military when tourniquets are not recommended or fail.^8,10 The active ingredient in Combat Gauze is kaolin an aluminum silicate that activates the intrinsic clotting pathway and accelerates clot formation.¹⁰ Application requires the wound to be packed with Combat Gauze and then direct pressure applied for three minutes or until bleeding stops.

Clinical Evidence

Most controlled studies on topical hemostatic agents come from animal models while retrospective studies are from the military with methodologies in these studies varying greatly.^{4,7,8,12,15,16} Comprehensive reviews of the literature related to topical hemostatic agents were published in 2006 by Pusateri et al¹⁵ and then in 2011 by Granville-Chapman et al.⁴ The most recent review, from 2014, by Bennett and Littlejohn⁸ discusses many of the new third generation products. The authors recommend consideration for the use of Celox Gauze and ChitoGauze, along with the currently accepted Combat Gauze used by the military.⁸ What is lacking is a depth and breadth of research specific to the use of topical hemostatic agents in the civilian prehospital setting. 

From the literature available, one study investigated the effectiveness of the HemCon Bandage in the civilian EMS.⁶ The bandage was added to the trauma kits of a fire agency, and medical personnel trained on the use of the dressing; receiving hospital personnel were also trained on product removal. During the study, 37 uses of the HemCon Bandage were recorded, and complete data sheets were available for 34 cases. The bandage controlled hemorrhage in 79 percent of the 34 cases, 74 percent within three minutes of application. In 74 percent (n=34) of the cases, direct pressure initially failed to control bleeding while the HemCon Bandage was effective in stopping bleeding in 76 percent of 25 cases.⁶ The HemCon Bandage failed to stop bleeding within 10 minutes in seven cases. The authors attributed six of the seven failures to user error. It was concluded that the HemCon Bandage was beneficial in stopping uncontrolled bleeding in the civilian EMS setting when traditional methods, such as direct pressure, failed. Proper training on the use of the bandage was stressed because user error was a contributing factor in most of the documented failures in the study.⁶ When cases with user error are removed from the analysis, the success rate increases to 97 percent, which aligned with previous research.¹⁷

TraumaDEX has also been investigated outside of military and animal models, and positive results have led to the support of this topical hemostatic agent in civilian settings.¹⁸ In this study, 29 healthy subjects had two incisions placed on their forearms. One incision was treated with TraumaDEX, and the other incision (control) was not. Both incisions were treated with 30 seconds of gentle pressure after the application of the TraumDEX to the test site, and bleeding times were recorded. TraumaDEX was found to have an 84 second average time to hemostasis compared with 381 seconds for a nontreated control site. Bleeding time was decreased by five minutes with the use of TraumaDEX compared to the control site.¹⁸

Additionally, 79 percent of subjects had immediate cessation of bleeding on the treated site. Seven days post treatment, no difference in the scar between groups was noted. The authors concluded that TraumaDEX’s improved bleeding times, and was beneficial because it is low cost and low risk.¹⁸

Clinical Use in Athletic Training           

There is no one-size-fits-all approach when considering topical hemostatic agents.¹⁵ Each situation varies, as does the wound’s location and structures involved (arteries, veins or both). Different topical hemostatic agents have different indications and contraindications for use. Athletic trainers need to review product information before purchasing any type of hemostatic agent and may want to consider purchasing more than one type of agent to meet the potential needs of the organization.¹⁹ Proper training must be provided for all staff members who might consider using topical hemostatic agents during an emergency.^6,7,10,16 The cost of various hemostatic agents is another consideration when selecting products. The price of different agents varies greatly between products and distributors (Table 2).

Application

The application of a tourniquet should also be considered prior to the use of any hemostatic agent. As discussed in Part One of this series, there is considerable evidence to support the use of tourniquets to control bleeding in the prehospital setting.¹ Topical hemostatic agents can be applied in addition to the tourniquet if bleeding is still not controlled.³ Table 3 addresses general steps for the application of a topical hemostatic agent.

Table 3. Steps for Using a Topical Hemostatic Agent in the Prehospital Setting

Step	Procedure
1.	Initiate body substance isolation procedures and activate the emergency action plan.
2.	Identify severe bleeding.
3a.	Attempt the application of direct pressure to control bleeding.
3b.	Proceed to tourniquet application when the inability to quickly control bleeding is identified.
3c.	Proceed to hemostatic agents when a tourniquet is contraindicated or the tourniquet is unable to control bleeding.
4.	Tear open the topical hemostatic device.*
5.	If using roll gauze impregnated with the hemostatic agent, tightly pack the unraveled gauze directly into the bleeding site. Pack as much of the dressing into the wound as possible.
6.	Pack the remaining wound cavity with standard gauze.
7.	Apply firm pressure directly to the wound for 3–5 minutes.
8.	Frequently reevaluate the injury site for active bleeding, increasing direct pressure as needed.
9.	Contact medical resources and advise of the application of a hemostatic agent; save the packaging to present to the receiving facility.
10.	Expedite transport to an appropriate medical receiving facility.

*Always defer to the manufacture’s recommendations for proper usage.

 

Indications, Contraindications and Precautions Indications

Topical hemostatic agents are recommended for use during vascular injuries that can’t be controlled by direct manual pressure alone.^3,4,7 Their use is especially key when hemorrhaging occurs in areas not amenable to tourniquet placement, such as the inguinal and axilla regions, thorax and abdomen, and over junctional hemorrhage.^3-5,7,20 Topical hemostatic agents should also be considered when a tourniquet is not available or fails to control bleeding.³

Contraindications vary based on the topical hemostatic agent and its main active ingredients; thus it is impossible to address all possible issues. In general, these products are not intended for internal (surgical) use, should not be used in the eyes, and are not indicated for use in the mouth according to the manufacturers of many of these products. For agents containing chitosan (from shellfish), patients may need to be questioned about shellfish allergies.^4,5 Always refer to manufacturer directions for a list of contraindications and precautions.⁵

Most topical hemostatic agents when applied still require two to five minutes of direct pressure to be effective, which was seen as a disadvantage in the military setting, but should be a nonissue working with  the physically active population in the civilian setting. Other precautions vary based on the topical hemostatic agents and their main active ingredients.

Conclusion

The use of topical hemostatic agents by athletic trainers was not always within our foundational education for a variety of reasons. Having the requisite training on a fundamental lifesaving skill is paramount given the likelihood of an athletic trainer being first on the scene of an emergency situation. In the presence of severe uncontrollable external hemorrhaging, when direct pressure and tourniquets fail and for areas where tourniquets are not amendable, consideration for the use of topical hemostatic agents is warranted.