Surgical and trauma patients are at significant risk for morbidity and mortality from bleeding and/or leaking bodily fluids. With the number and complexity of surgeries rising, so is the need for better hemostatic agents to stop bleeding as quickly as possible.
The history of approaches to hemostasis goes back to when people simply used their hands or a tool to apply to a wound to stop bleeding. In fact, even today, the first solution we use when trying to stop bleeding tends to be pressure. In surgical suites, surgeons can use a hierarchy of tools to stop bleeding, including pressure, cautery, animals-derived materials (gelatin, collagen), plant-based materials (cellulose) and synthetic materials. Surgeons can also use more active products, including fibrin sealants and/or thrombin, which are based on proteins the body makes in order to stop bleeding.
Animals, including humans, have built-in mechanisms to stop bleeding. Our blood vessels constrict (narrow) to some degree. We also have platelets and something called the “coagulation cascade.” When we bleed, the coagulation cascade is set in motion. The coagulation cascade consists of a series of proteins, each of which is activated in a cascading sequence, the end product of which is a fibrin-platelet plug, better known as a clot. And bleeding stops.
Of course, the coagulation cascade must be functional in order to work—some patients have defects in their coagulation cascade or in their platelet function, and others are on medications to prevent clots (anti-thrombotics such as anti-platelet drugs and anti-coagulants). Collectively, patients know these drugs as “blood thinners.” These patients are common and many of the known tools mentioned above do not work well in them.
Unfortunately, these available solutions possess various limitations. For example, they are slow to work—most take minutes, which could cause excessive blood loss—and lack reliability, as many are patient-dependent. Some can cause immune responses and healing problems, as the body can view the solutions as foreign bodies and react to them, especially those derived from animals. Some can cause adhesions, which are frequently negative consequences of the surgery itself made worse by the materials. There’s also the drawback that many of these materials aren’t easy to make or use in most surgical cases. And some of these materials are derived from technologies that are significantly expensive to use.
These limitations have opened the door for better-performing hemostatic products. Among the contenders in this area is Arch Therapeutics of Wellesley, Mass. The company is developing the AC5 Surgical Hemostatic Device, which is being designed to achieve prompt hemostasis in laparoscopic and open surgical procedures. Arch Therapeutics spoke with surgeons, operating room managers, sales representatives for competitive products and hospital administrative decision-makers in order to incorporate what they want in an ideal product into AC5.
AC5 is a synthetic peptide comprising naturally occurring amino acids. “These amino acids are found in your body,” says Terrence W. Norchi, MD, President and CEO of Arch Therapeutics. “This is one of the reasons that patients should have a degree of comfort that they won’t face the negative consequences seen in animal-derived materials, and that the solution won’t be seen as a foreign body and elicit an immune response.”
The AC5 peptide is put in a clear liquid solution—which, from a consistency basis, is akin to Purell—and then squirted or sprayed directly onto a wound. The moment AC5 hits the wound, the transparent liquid moves into the nooks and crannies of the connective tissue where it self-assembles itself into a lattice-like gel and stops the bleeding or leaking within seconds, according to Norchi. As AC5 is transparent and neither sticky nor glue-like, its use is ideal for laparoscopic surgery.
Unlike existing hemostatic agents, AC5, says Norchi, possesses a combination of advantages to benefit surgeons, wound care specialists and patients. Based on work to date, he sees evidence that it is laparoscopic-friendly, is simple to prepare and store, is non-toxic and non-immunogenic, and is easily applied and handled. Because AC5 is transparent, Norchi says, it can promote a clear field of vision and not obstruct the surgeon’s view. In fact, he says, a surgeon can operate through it in order to prophylactically stop bleeding as it starts.
Importantly, Norchi says, that based on its mechanism of action, he expects AC5 to be indifferent to whether a patient is on “blood-thinners” or has a malfunctioning coagulation cascade, as this would open up the market significantly. Norchi looks forward to when Arch starts to do the work in subsets of these patients, as it should add great value to the company’s prospects.
And although AC5 is a development-stage product, Arch Therapeutics hopes to reach human models in the not-so-distant future. However, initial work has been done using the peptide for hemostasis in rodents and was published in 2006 by Rutledge G. Ellis-Behnke, PhD, a co-founder of Arch Therapeutics and an advisor. The company has also done work in large pigs with positive outcomes.
“We are excited about our potential to improve the landscape of the surgical and interventional medical world—it is what we think about daily,” says Norchi.
The hemostatic and sealant market in aggregate is a large market. MedMarket Diligence estimates that the market reached $4.5 billion in 2013 and should surpass $6.5 billion in 2017. The question then becomes how the market will change with many already-situated products.
“I think that many products currently on the market will remain, but most surgeons that we know seek something better,” says Norchi. “So there is opportunity and room for many new and better products to enter the market. The question then becomes, are those new products available to fill the need?”
Arch Therapeutics has developed a network of European and American collaborators in academic institutions and industry. As an example of the company’s cooperative development model, it has a fostered a successful multi-year relationship with institutions within the National Univ. of Ireland. Collaborations with Univ. College Cork, Univ. College Dublin and the Royal College of Surgeons in Ireland received support from the prestigious Science Foundation Ireland. In current and prior partnerships, Arch Therapeutics’ leadership, technology and resources have combined with Irish academic institutional scientists and assets in order to drive product development.
As the surgical field places more pressure on surgeons to operate less invasively and in an increasingly outpatient setting, there is a need for more advanced technologies to help them meet this goal.