and strong tissue adhesiveness. It shows high survival in lethal extremity arterial haemorrhage cases. However, significant endothelial and transmural damage was observed in WoundStatTM-treated vessels, which also exhibited thrombi and embedded WoundStatTM residues. Although it has been proved to be an effective haemostatic agent, use of WoundStatTM was associated with a substantial local inflammatory response and neurovascular changes up to 5 weeks post-injury [22]; consequently, the US Army halted the use of WoundStatTM powder, only months after approving it.
bleeding surfaces in various physical forms. Chitosan-based haemostatic agents that have been approved, are commercially available and applied clinically to accomplish haemostasis are detailed in Table 7.3.
Table 7.3 Commercially available chitosan-based haemostatic agents
Hemostat Mode of action
HemCon®, HemCon Medical
Technologies Freeze-dried chitosan acetate sponge Chitoflex®, HemCon Medical
Technologies
Dressings designed to reduce moderate to severe bleeding
Chitoseal™, Luna Innovations, Inc. Rapidly polymerising gel with a cellulose coating for haemorrhaging wounds
ChitoGauze®, HemCon Medical Technologies
Highly flexible, uniquely formulated, chitosan coated haemostatic gauze dressings
TraumaStat, OreMedix, Lebanon Chitosan with silica and polyethylene to produce a product, such as gauze, that is conformable Hemogrip™, Remedium Technologies Highly tissue adhesive chitosan bandage
Celox™, SAM Medical Chitosan-based granules, such as Celox™ granules and Celox™ A. Celox™ gauze is a high-density gauze impregnated with chitosan granules
Chitipack®, Eisai Co. Sponge-like chitin for traumatic wounds Vulnosorb, TeslaPharma Freeze-dried sponge composed of chitosan and
collagen SyvekExcel™, Marine Polymer
Technologies Inc.
Utilising chitin fibres in a unique lyophilised 3D form
Chitodine, Industria Chimico- Farmaceutica
Chitosan powder with adsorbed iodine 3D: Three-dimensional
7.4.1 HemCon®
Hemcon® is an FDA (2003) and Conformité Européene approved haemostatic dressing for external application and consists of a deacetylated chitosan acetate salt on a sterile foam backing pad. On contact with anionic erythrocytes, the chitosan salts rapidly ‘crosslink’, adhering strongly with the wound surface. This adhesive process is thought to be the primary mechanism of action; independent of platelets
or clotting factors [24]. HemCon® has been deployed by the US Military since 2003 and was initially issued to special operations medical staff, later as personal issue for deployed US army soldiers; it is also issued to medical personnel in the UK Armed Forces. Enhanced HemCon® bandages are now in production which are thinner and more pliable than the original product, and designed to allow better conformation to the wound surface and easier handling. HemCon® medical technologies have produced a double-sided flexible roll of chitosan, called Chitoflex®, which has been tested in some of the more recent animal studies. The literature reports a 97% success rate at controlling the bleeding of human subjects [25]. Chitoflex® is made of the same material as HemCon® and provides the same life-saving technology, but is available in a strip form and can be used to pack wounds. It is available in a variety of lengths and in rolls for easy application by medical professionals, as shown in Figure 7.3.
Figure 7.3 Chitoflex® haemostatic dressing by HemCon® Medical Technologies Inc., is manufactured from chitosan and becomes extremely adherent when in contact
with blood and this adhesive-like action seals the wound and controls bleeding
7.4.2 Celox™
Celox™, is a new product approved by the FDA in 2005 for use as a haemostatic agent.
Celox™ is a chitosan granule flake that works to promote clot formation through adsorption and dehydration, and the promotion of red blood cell bonding. The
proprietary composition has a high surface area and special purification procedure to make it more effective. When it comes in contact with blood, it swells, gels and sticks together, forming a gel-like clot which engulfs cells inside the clot. Figure 7.4 shows the flake granules of Celox™, the formation of a clot with blood and its application on a wound. It does not interfere with the body’s normal clotting cascade and can even clot blood containing anticoagulants such as heparin and coumadin. This free-flowing powder needs to be poured onto the wound area and pressure should be applied for up to 5 min to stop the bleeding. It is a potential life-saving product that can even be used at home. Celox™ is also available in pad and gauze form which are embedded with Celox™ granules. A recent trial of effectiveness demonstrated the equivalence of Celox™ with HemCon®, and QuickClot® in controlling haemorrhages [26].
Figure 7.4 Celox™ granular flakes forming a clot in the presence of blood and its application on the wound
7.4.3 HemogripTM
Hemogrip™, produced by Remedium Technologies, creates a nanoscale 3D mesh, which rapidly coagulates blood and stops bleeding instantly. It is also available as a high-pressure sprayable foam that can expand into an injured body cavity; it will adhere to tissue and stops bleeding within minutes of the expanding process. It has been reported to be superior to unmodified chitosan sponges or standard gauze for controlling bleeding from a lethal arterial injury [27]. SyvekExcel™ is a noninvasive vascular access haemostasis system which utilises chitosan and with its 3D fibrous structure achieves faster, easier and effective haemostasis. Accelerated and complete haemostatic action is achieved even in patients taking anticoagulants such as heparin, clopidogrel and aspirin. Chitosan-based haemostatic agents have become one of the most promising agents in reducing pre-operative and post-operative bleeding.
Various forms of chitins and chitosans have been used to promote haemostasis in experimental studies as well as clinically, even in battlefield environments. Although the haemostatic action of chitosan is known to be initiated by the agglutination of red blood cells and chitosan’s strong bioadhesiveness, which causes clot formation, the detailed mechanism of action and cell signalling pathways involved are not yet known. Researchers are still in the process of developing improved chitosan-based haemostatic dressings.