By Don Vaughan

Urban wildfires have plagued the western United States for several years, fueled in many areas by severe drought. Such events can be catastrophic, devastating communities and sending homeowners fleeing.

In addition to the physical and monetary damage caused by urban wildfires, a new study from researchers at the University of California, Davis Veterinary Medical Teaching Hospital has found cats injured in such events are at significant risk of developing deadly blood clots. The study, published in the journal, Frontiers in Veterinary Science, follows another which showed that cats injured in urban wildfire also had a higher incidence of heart problems.

"The first really big incident was the 2017 Tubbs Fire," says lead co-author, Ronald Li, DVM, MVetMed, PhD, DACVECC, associate professor of small animal emergency and critical care, department of Veterinary Surgical and Radiological Sciences, University of California, Davis School of Veterinary Medicine. "That's when we started treating a lot of cats with wildfire injuries and began noticing many had respiratory diseases and some of them had sudden deaths."

Dr. Li and colleagues began performing echocardiograms on the injured cats and found many of them had myocardial changes. "We could see the formation of blood clots inside their hearts," Li says. "This raised very interesting questions on why injured cats were having these myocardial changes and forming clots in their hearts."

The opportunity to look further into the relationship between urban wildfires and cardiac issues in cats came the following year, when California experienced even worse wildfires. The 2018 Camp Fire, for example, resulted in at least 85 civilian fatalities and destroyed more than 18,000 structures. It is considered the most devastating wildfire in California history.

Li collaborated with the hospital's cardiology team to look at the platelets of cats that had been burned or experienced smoke inhalation during an urban wildfire.

"We knew previously from our studies that cats with heart disease naturally have hyperactive platelets, so these cells are responsible for stopping bleeding elsewhere in the body," Li explains. "However, when they are in overdrive, they can spontaneously cause clot formation. We started looking at all cats that came through at one time, and that's how the study began."

Study patients and findings

The most recent study comprised three groups: cats injured in urban wildfires (mild injuries to significant burns), asymptomatic cats with hypertrophic cardiomyopathy, and a control group of healthy cats.

"We found cats injured in wildfires have even more hyperreactive platelets than cats with just heart disease," Li says. "This shows this is likely an independent event from heart disease, it's likely from the [wildfire] injury itself. Our study found some pretty novel stuff that was not previously seen in naturally occurring wildfire models before. We had data from animal models such as rats and mice that were treated with particulate matter, and we know from those studies platelets do somehow play a role. But this was the first time anyone has found platelet activation in naturally occurring victims."

Interestingly, the cardiac issues found in cats injured in urban wildfires do not associate with severity of burns, Li says. "Throughout our analysis of data, we created a model and included different factors such as white blood cell count, burn severity, and our platelet activation data," he says. "What we found is platelet activation in response to the activator arachidonic acid was the only independent factor that causes these heart changes and clot formation inside the heart. Personally, I believe burns likely have to combine with smoke inhalation to cause a lot of the cardiac changes we are seeing."

According to Li, previous research into how platelets interact with particulate matter released in wildfires, including rat models, also showed platelets are more activated. This laid the groundwork for the most recent studies.

"We came in with a hypothesis that in naturally occurring victims, platelets do play a role in clot formation within these cats, and this supports recent data that during wildfire season, visits by people to emergency departments are markedly increased for cardiovascular events, stroke, and respiratory signs," Li says. "We have known for a long time firefighters have an increased risk of stroke and cardiac issues, but we never really understood the underlying pathophysiology. This is the first study looking at a naturally occurring model."

Taking a toll

An intriguing sidenote of the most recent study was the discovery of a novel receptor on cat platelets called toll-like receptor 4 (TLR4), which may play a role in clotting and could be the target for future treatments.

"Toll-like receptors are usually found on immune cells, and platelets are no exception," Li says. "We have found their level of expression varies among cats, so our hypothesis is that in disease states such as wildfire injuries and smoke inhalation, these expressions are up-regulated. We are currently publishing a study on toll-like receptor 4 that showed these receptors turn on all the machinery. They don't necessarily cause platelets to clot, but they function to shut down the inhibitory pathway, so those platelets become hyperreactive. We just got a grant from The Every Cat Health Foundation to look at toll-like receptor 4 expression in cats with heart disease."

The mechanism behind the adverse health effects of urban wildfires in cats remains a mystery, though there are theories, Li says. The most prominent revolves around the role of platelets in inflammation and immunity, as well as clot formation.

"We believe that platelets probably have a lot to do with vascular changes," Li explains. "They probably interact with white blood cells to infiltrate the heart, causing ischemia and other heart changes. This certainly opens the door for future studies."

Fire types matter

It is important to note how urban wildfires differ from traditional forest fires. In the latter, only trees burn. In the former, human-made structures are also destroyed, producing noxious gases and other hazards as they burn. "Data shows urban wildfires are much more negatively impactful on cardiovascular health than wildfires alone, mainly because of noxious gases produced by burning plastics," Li says. "It has a huge impact on human and animal health."

Research into the cardiac effects of urban wildfires has almost exclusively focused on cats because they are natural survivors. "During natural disasters such as wildfires, cats hide, whereas dogs, because of their temperament and personalities, tend to stay with their owners," Li explains. "Cardiac issues could occur in other species, but cats are a bit unique in terms of how their platelets function. I know that because I study platelets of a lot of species, and cat platelets are by far the hardest to work with because of how reactive they are. I think there is a species difference, but I cannot rule out whether it happens in other species."

Cats injured in wildfires receive wound management, pain management, and supportive care. However, the recent study found that plain aspirin may play an important role in treating the formation of blood clots in the heart. "The pathway that is inhibited by aspirin is significantly elevated," Li says. "We found in cats that had a physical clot on a heart scan, that pathway was out of control. So, aspirin has its place in targeting a specific pathway. This links back to the toll-like receptor 4. We're going to work more to see if the toll-like receptor 4 can stimulate the aspirin pathway and whether they are interlinked."

Don Vaughan is an award-winning writer who frequently writes about veterinary-related topics.