Page 156 - JSOM Summer 2020

Influence of Celox Rapid’s Mode of Action Under
Normal and Compromised Blood Conditions

Andrew Hoggarth, BSc, MSc; Matthew Grist, MChem, PhD, CChem;
Toni Murch, MCPara

here have been significant advancements in scientific un- its guidelines for control of hemorrhage as hemostatic agents
derstanding and technology with respect to bleeding and for military-wide use. Already in use by US Special Forces, the
Themostasis. Despite this, trauma remains a leading cause CoTCCC decision now makes Celox available to every mem-
of human morbidity and mortality. Assessment of the types of ber of the DoD. Celox Rapid is the latest development in the
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trauma reveals that hemorrhage is the main cause of prevent- Celox Gauze range of products.
able death in both combat and civilian trauma situations. To
2–4
complicate this scenario, approximately 25% of severely in- Celox Rapid has been formulated to have a distinct and effec-
jured patients have an established trauma-induced coagulop- tive mode of action, which is designed to work independently
athy on arrival at the emergency department, a phenomenon of the clotting cascade and not be affected by any potential
associated with an increased rate of early and late mortality. changes within the blood system.

Trauma-induced coagulopathy is caused by several factors as- The primary mode of action is a device function comprising
sociated with the trauma itself as well as certain interventions of the formation of the gel plug to stop bleeding. Within this
undertaken and results in a disposition toward a slower co- mode of action there are two key elements. The first element is
5–7
agulation process. Although trauma-induced coagulopathy is the gelling action, the second element is the adhesive proper-
multifactorial, it is definitively the most important issue for ties of the gel around the newly formed gel plug.
the management of severe trauma patients. Rapid hemor-
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rhage control is one of the key areas of support within the The first element of the primary mode of action is when the
medic’s arsenal of devices. While the tourniquet is the first line chitosan-based granules contact aqueous fluid the chitosan
of treatment in the majority of injuries, areas requiring com- chains extend due to the electrostatic repulsion between the
pressible hemorrhage control not amenable to limb tourniquet protonated amines and the solubilizing effect of the fluid. Ef-
use or as an adjunct to tourniquet removal remain strategic fectively, the chitosan chains are dissolved into the fluid. Once
management. These areas require a hemostatic product. extended, the chains form a mesh-like structure linked with
both chain entanglement and a newly formed intermolecular
A review of the extensive literature on hemorrhage control and intramolecular hydrogen bonding network that occurs
highlights that not all scenarios are the same, and the patient’s through the absorbed water molecules. The effectiveness of
condition, both externally and internally, plays a significant the hydrogen bond network is driven by the proprietary and
part of the efficacy of the treatment provided. One of the key unique chitosan formulation within Celox Rapid. This gives a
goals, therefore, is to ensure that the treatment is as effective gel structure that, once formed, does not easily dissolve in or
as possible in all situations to provide the optimal chance of absorb further fluid. This is due to the chitosan chains now
survival. being in a low energy state compared with the initial globular
form and the new hydrogen bonding network being in place.
When assessing junctional hemostatic devices, the prominent Laboratory testing demonstrates the ability of the proprietary
and most reported product types split into two categories: chitosan-based granules to absorb fluids from the body, which
those that primarily affect and promote the body’s natural includes whole blood, anticoagulant-impregnated blood, and
clotting cascade and those that primarily absorb the excess diluted anticoagulant-impregnated blood at a range of tem-
fluid and gel and create a robust gel-like plug. Both product peratures (4.3° C–55° C, including the normal condition of
categories play a significant part in aiding the survival of the 37° C and hypothermic condition of 35° C), within 60 sec-
patient following injury. onds. The gel created in all of these scenarios has very similar
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properties in terms of viscosity, density, and robustness, indi-
The purpose of this paper is to review the role a proprietary cating that the product efficacies are similar irrespective of the
chitosan-based hemostatic agent (Celox Rapid), which absorbs profile of the blood.
fluid to create a gel-like plug, potentially plays in managing
and controlling bleeding in normal and compromised condi- The second element of the mode of action is the bioadhesive
tions. The US Department of Defence’s Committee on Tactical nature of the product. This is achieved in two ways. The pri-
Combat Casualty Care (CoTCCC) has added Celox Gauze to mary method is via the bioadhesive within the formulation.
Correspondence to Nick.Tsiakas@medtrade.co.uk
All authors are employees of Medtrade Products Ltd., Cheshire, England.

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