Author: Tricol Biomedical

In our final article of our first of many educational series, we are going to review the body’s natural clotting cascade and how HemCon’s hemostatic devices do not rely on this process to control bleeding.  We often talk about how our products work “outside of the clotting cascade” but what does that really mean? What is the clotting cascade and why does it matter that HemCon products work outside of it?  First, we must understand the clotting cascade. By quickly glancing at the diagram on this page, it will make perfect sense…. Well, perhaps an explanation is necessary. The human body is full of complex processes that are truly amazing, and the clotting cascade is certainly one of them.

Don’t worry about the above diagram. What you need to know is that when you cut yourself and you want the bleeding to stop, or when a physician performs surgery and needs to stop the bleeding post-procedure, there are many things within your bloodstream that need to happen for it to successfully form a clot. In fact, there are 13 “clotting factors,” and each factor has an “inactive” form that gets converted into an “active” form to enable clotting. This conversion is the clotting cascade.

Before we go further, let’s get some common definitions out of the way:

1. Clotting Factors – any of several substances in blood plasma that are involved in the clotting process, such as calcium, prothrombin, Fibrogen, and tissue. Each clotting factor is assigned a number 1 through 13.
2. Collagen – the main structural protein found in the skin and other connective tissues.
3. Prothrombin – a protein in blood plasma that gets converted into thrombin.
4. Thrombin – an enzyme in blood plasma which causes the clotting of blood by converting fibrinogen into fibrin.
5. Fibrinogen – a soluble protein in blood plasma from which fibrin is produced thanks to the action of thrombin.
6. Fibrin – an insoluble protein formed from fibrinogen during the clotting of blood. It forms a “fibrous” mesh that impedes the flow of blood… the clot!
7. Platelets – small cells in the blood that help with forming blood clots.

When there is damage to a blood vessel (from an unanticipated cut, or surgical procedure), collagen is exposed to circulating platelets in the blood. These platelets bind directly to collagen and create a platelet plug. This is the first thing that happens, triggering the clotting cascade. We mentioned above that there are 13 factors that need to convert from inactive to active inside the clotting cascade.  These 13 factors are organized in what is referred to as pathways, the intrinsic pathway and the extrinsic pathway. The intrinsic pathway is activated when there is direct damage to the blood vessel.  The extrinsic pathway is activated by direct damage to the blood vessel as well, but also by many other things such as tissue damage outside of the blood vessel, hypoxia, sepsis, malignancy, and inflammation. Think of these paths as separate roads, each with different factors with conversion processes that ultimately come together at factor 10 to form one road, starting the common pathway.  And within the common pathway, the 2 most important factors are thrombin and fibrin.

Fibrin is factor number 1, the protein that forms a mesh, trapping platelets and ultimately creating the clot. But it cannot happen without thrombin, factor number 2, which plays a big role in activating many of the other factors, both within the intrinsic and extrinsic pathways (factors 5,7,8,11 and ultimately 13). Factor 13 is the last and final clotting factor number.  When you’ve reached factor 13, your blood has formed a clot!

By now you are an expert at understanding the body’s natural clotting cascade. Maybe not, it can be confusing even for those that are somewhat familiar with it. It is truly amazing that this process takes place every day in all of us when we cut ourselves or have a planned event. And now that you know about it, we can get back to the original question of how the HemCon hemostatic devices work “outside of the clotting cascade,” and why it matters.

If you cut yourself and use a store-bought bandage or piece of gauze, and apply gentle pressure to stop the bleeding, you will need the clotting cascade to kick into gear and allow the process to run its course, ultimately creating a clot (thrombin to fibrinogen to fibrin). Think about all the factors mentioned above! This process works fast in some people, and very slow in others. For patient’s on blood thinners (anti-coagulants) their pace of clotting is slowed by impacting certain factors limiting thrombin’s ability to exercise its power in creating a clot. There are also certain diseases like hemophilia or Von Willebrand disease that hinder the ability of the clotting cascade in affected individuals. The clotting cascade does not always cooperate as it does on paper and charts.  Getting the clotting cascade to work could take a very long time in some cases.

This is where “working outside the clotting cascade” comes into play for the HemCon hemostatic devices. Our positively charged chitosan devices simply attract the negatively charged platelets and blood cells to create a strong clot at the wound site, meaning, you do not have to worry about all those factors in the clotting cascade running their course. Of course, they will run their course behind the scenes, but HemCon devices do not rely on them at all. Other hemostatic devices made from other sources work by affecting the extrinsic pathway, speeding up the clotting cascade process, but still must rely on part of the clotting cascade being intact.

The HemCon hemostatic devices have been stopping bleeding since 2001 when first introduced by the U.S. Army to control traumatic bleeding. Being able to “work outside of the clotting cascade” played a large role in their decision to supply HemCon products to U.S. Soldiers.

It has been over one year since the world was shut down in response to COVID-19. Since then, the general population has become more in tune with proper health and safety practices such as washing hands and wearing masks. Wearing a mask has become an important practice used to prevent respiratory droplets from reaching others. Face masks have found their place as a simple barrier to aid in the prevention of illness. Shouldn’t it be just as important that your injuries, whether through planned hospital procedures or unexpected events, are provided that same protection?  Many of HemCon’s bleeding control products provide an antibacterial barrier against 24 microorganisms.

As you learned in article 2 of this series Chitosan Performance in the Human Body, the HemCon bandage type dressings provide a technology that adheres tightly to blood and seals the injury site to stop bleeding. Equally important is that this adhesion process also provides an antibacterial barrier, blocking the ability of bacteria to penetrate the wound.

Proper application and removal of HemCon products play an important role here. When HemCon Chitosan dressings come in contact with blood, they essentially create an instant clot, adhering to the wound, creating a very tight seal that can’t be penetrated. The dressing can be left in place on the patient for up to 48 hours providing continuous protection! However, improper technique could jeopardize this important safety feature. Lifting up the dressing and peeking underneath to see if bleeding is controlled can break the strong seal and could compromise the dressing’s ability to provide the bacterial barrier. (Note: Not all HemCon dressings provide this barrier to bacteria. Check the product descriptions on our website for products that carry this claim.)

The antibacterial barrier of HemCon dressings was investigated using a standardized test method, Evaluation of Antibacterial Finishes, where the dressing was exposed to single strains of Staphylococcus aureus (MRSA), Enterococcus faecalis (VRE), and Acinetobacter baumannii. HemCon bandages exhibited a >99% reduction in organisms 24 hours after being exposed to the dressing. The most common microorganisms causing surgical site infection are Staphylococcus aureus and enterococcus faecalis. (Read the full article here.)

The unique properties of chitosan, the correct delivery matrix for the wound type, and good clinical practice produce a powerful barrier against some of the most prevalent bacteria found in hospitals.

Tricol’s chitosan is derived from shrimp shells. Yes! We learned all about this metamorphosis in Article 1 in this series – Chitosan Unleashed!  As you can imagine, there are many complex propriety steps that happen between the extraction of chitosan from shrimp, and the point of using a finished product to control bleeding wounds in a caregiver’s hands. Our various products are stopping bleeding all around the world!  You can find them in hospitals, outpatient settings, long-term care facilities, schools, places of work, and homes. They are trusted by first- responders in our communities and on the battlefields we serve. Many users want to understand the technology behind our life-saving products. This stuff works, but how?

If we get into the science just a little, chitosan is positively charged. When it comes in contact with blood, it attracts negatively charged red blood cells and platelets that are drawn to the positive charge, creating a very tight seal. Think of a magnet. This ionic interaction produces an extremely strong, mucoadhesive (sticky) seal. This supportive seal at the wound surface works quickly to stop bleeding. Chitosan technology has been proven to work even on individuals suffering from abnormal blood clotting mechanisms, or those on blood thinners. Our chitosan technology works independently of the body’s clotting system (clotting cascade). Check back later for an article on bleeding and the clotting cascade!

There are many ways in which the human body bleeds.  It could be the result of a traumatic injury, or, as a by-product of a medical procedure or intervention. Whichever way, chitosan needs to be delivered to the source of bleeding via an appropriate support matrix. In other words, for different types of bleeding, Tricol chitosan products are delivered in different forms. Although the forms are different, they have in common the need to be strong, interconnected, and porous which allows them to adhere to blood-wetted surfaces and to resist high pressures from the vascular system.

Tricol products are broadly categorized into two general “family” types that we refer to as the “bandage family” and the “gauze family”. Although they are both derived from the same shrimp shells off the pristine coast of Iceland, they treat different types of wounds.

Our bandage family is essentially freeze-dried chitosan. It is very soft in its finished form. This is not the type of bandage you would find on the shelf of your local pharmacy or grocery store. It is the kind of bandage you would find in the kits of the U.S. Army’s Special Forces Green Beret unit or in the hands of the paramedic that arrives on the scene. In fact, your cardiologist, trauma surgeon, or local dentist may be using this same battlefield-tested product on you. It is extremely safe and effective in controlling severe bleeding in minutes. It’s great for cuts and lacerations. This product family used to be available only to professionals but is now available to the civilian population as well.

Our gauze family of products are flexible, chitosan-coated gauze dressings that come in a variety of different dimensions and lengths. Whereas our bandage family of products is used to quickly control surface level cuts and/or lacerations, our gauze family of products is typically used for deep penetrating wounds, or when the source of the bleeding is below the surface and not visible. These dressing are then “stuffed” into the wound to come in contact with the source of bleeding. These gauze dressings are now also available to the civilian population just like our bandage family.

Tricol’s specific products in both the bandage and gauze families are now being produced and provided for consumer and home use as well.

Check back here soon for the next article in our Chitosan Unleashed series where we will explore the anti-microbial properties of chitosan-based bleeding products.

Chitosan is the active agent in Tricol Biomedical’s HemCon and OneStop hemostasis products and in order to understand how it works, you should first know about chitin. Chitin is the second most abundant naturally occurring biopolymer, after cellulose. In the natural world, chitin functions as scaffold material that gives structure and strength to insect exoskeletons and crustacean shells, and it is also found in mushrooms. It is often found in association with the mineral calcium carbonate. Our chitin is sourced from shrimp shells of the species Pandalus Borealis. The species naming is a reference to the Aurora Borealis found in the sky above the pristine waters of the North Atlantic Ocean. The shells that are received for processing at Primex  in the very north of Iceland are collected under carefully regulated quota systems that leave a sustainable balance to the marine environment. These quotas are based on scientific criteria for sustainable utilization of natural resources and the dedicated work of the Marine Research Institute.

Once the chitin is extracted from the shells, it undergoes a process called de-acetylation that molecularly transforms the chitin to chitosan. So now that we know where chitosan comes from, what exactly is it? Chitosan is a natural biopolymer that possesses a positive molecular charge and is the hemostatic component in HemCon bandages and coated gauzes. This positive molecular charge is the basis of chitosan’s medical uses. For bandage and gauze products like ours, the positive charge attracts negatively-charged blood cells like a magnet, rapidly creating a tight seal over an injury.

Often a first reaction to the use of chitosan in medical devices are concerns with shellfish allergies. Most allergic reactions to shellfish are caused by the protein part of the shellfish, not by the shells. Any residual proteins are eliminated during the conversion of chitin to chitosan. There have been no reported cases of an allergic reaction to our chitosan products in the 20 years we have made them. Keep an eye out for more detailed information to come on the use of chitosan by people with shellfish allergies!

Due to chitosan’s many attractive properties such as its natural origin, abundance, and positive charge reactivity, it has a multitude of real-world applications. You can find chitosan used in the medical field, agriculture, food processing, cosmetics, and water treatment. Chitosan is a prime example of how we can use technology to benefit from naturally occurring materials. And as a bonus, HemCon chitosan is made as a byproduct of the shrimp fishing industry, so our material sourcing helps prevent waste and minimizes our environmental footprint.

Now to answer the question on everyone’s mind: how do you pronounce chitosan? Is it ‘cheeto-san’ or maybe ‘chyto-san’? When you find yourself in a conversation about all the benefits of chitosan, you can confidently pronounce chitosan as ‘kai-tuh-san’.