Bleeding from a major injury can  be even worse than you think.

Obviously it’s dangerous that  you’re losing lots of blood, but strangely, massive blood loss can  also be dangerous because of blood clotting in the wrong place: inside blood  vessels far from the site of injury.   This is not great when doctors  are trying to save someone suffering from serious injuries, and  we’d really like to know why it happens.   Now one research group is suggesting there's hope… from an ingredient used in perfume. [♪ INTRO] Blood clotting is tightly controlled in the body. Too little is bad, because it means  you’d keep bleeding if you get cut.

But too much clotting is bad too, because  it can lead to clots forming in the bloodstream, potentially blocking blood  vessels and leading to organ damage.   Each extreme even has a  genetic disorder to go with it: hemophilia for too little clotting,  thrombophilia for too much. You really do want to be  in that Goldilocks middle. So you would think the case  of blood loss is firmly in “too little” territory,  but blood clotting is weird.

Patients with heavy bleeding,  say from traumatic injury, can sometimes also experience coagulopathy, where you can get too much clotting,  too little, or sometimes even both. Injury was the leading cause of death in  people ages one to 44 in the US in 2019. Although coagulopathy doesn’t  happen in all cases of injury, it’s still a problem in many trauma patients.   The thing is, we’re still not  sure what causes coagulopathy, but recent research points to something  called glycocalyx being involved.   The endothelial glycocalyx is a  coating made from protein and sugars that lines the inside of blood vessels.

It’s essentially an anti-blood-clotting  coat, separating blood from the so-called endothelial cells  that make up the blood vessel tubes.   If glycocalyx gets separated from the  endothelial cells it’s anchored to, those cells basically become  platforms for clot formation. This sort of makes sense: if the  body detects shed bits of glycocalyx, that could mean injury to the blood vessel; so clotting would be the appropriate response. The problem is that glycocalyx shedding can happen in places far away from the primary injury.

In trauma patients who have  suffered massive blood loss, it seems to happen when  cells are deprived of oxygen for a while and suddenly get oxygenated again. So in addition to hemorrhaging, these  patients could have glycocalyx shedding, leading to dangerous clotting  in other parts of the body. That is, coagulopathy.

But why would getting oxygen back be a bad thing? In a 2023 study published in Science Advances, a research group suggested the molecule succinate, and the enzyme succinate dehydrogenase,  may be key players here.   Basically, succinate is part of normal  energy production in the mitochondria, which use oxygen and some raw materials  in a cycle to generate energy. Without oxygen, the cycle gets stuck and  succinate builds up in endothelial cells.

When cells get oxygen again,  the succinate is rapidly moved along to the next step in the  cycle by succinate dehydrogenase. None of that has to do with coagulopathy, exactly, but the fun part is that this reaction has  byproducts called reactive oxygen species, or ROS for short, and they very much do. These are pretty much what it says  on the tin: they contain oxygen, they’ll react with whatever’s closest,  and they’re generally a nuisance.

Normally cells can deal with that,  but with a build-up of succinate, there are suddenly higher levels  of ROS than cells can handle.   There’s a lot going on, but basically,  ROS lead to a bunch of bad-news chemical reactions that  eventually lead endothelial cells to cut loose the glycocalyx from their surface. Leaving the cells exposed and liable  to become sites of clot formation.   Moreover, the shed glycocalyx pieces  can cause a different problem. Their anti-clotting properties can  prevent clotting elsewhere in the body, so you’ve got too little and  too much clotting all at once.   In that 2023 study, the  researchers used a molecule to block the succinate dehydrogenase  enzyme both in vitro and in rodent models.

They showed this could prevent glycocalyx  shedding, and ease coagulopathy. Without the molecule, more than  50% of rats in their experiments died from coagulopathy  complications following injury. But in rats treated with the molecule  following injury, there was 100% survival.

This molecule was dimethyl  malonate, or DMM, a compound widely used in perfume-making to  create jasmine-smelling fragrances.   The research also showed that  succinate and glycocalyx damage was elevated in trauma patients with coagulopathy, just like in the rodent model, so DMM may point towards a treatment in humans too. Blood clotting is complicated,  and there are many other factors that can lead to things going out of balance, so fixing glycocalyx shedding is  likely just one piece of the puzzle. Still, DMM worked well enough in  these models to be encouraging, and that could mean it has  potential as a therapeutic tool.   The authors don’t go so far as  to propose DMM for human use.

Like, it’s not a drug and  has never been tested as one. So we’d need to find out if it’s even safe  to give to people, never mind effective. Or we’d have to develop something else, say a new drug to block succinate  dehydrogenase, based on this lead.   Still, if it checks out, the scent of  jasmine flowers could signal hope for people with severe bleeding – great news  for patients and doctors everywhere.

Thanks for joining us for this episode of SciShow. We love talking about the unexpectedly  great things science can do, like potentially developing  lifesaving treatments from perfume. In order to do that, we have the help  of some amazing people: our patrons!

You guys genuinely make what we do here possible. As thanks, patrons get access to neat stuff like bloopers and behind-the-scenes peeks. If you’d like to join our incredible community, you can get started at patreon.com/scishow. [♪ OUTRO]