Common Blood Thinners Could Combat Snakebites, Preventing Tissue Damage and Amputations, Study Finds
An estimated 400,000 people per year are permanently disabled because of snake venom, which can cause lesions and necrosis at the bite site
When cobras attack, they use their fangs to inject a powerful venom into their victims. A snakebite patient then faces a race against time to reach a hospital, where doctors can administer antibody-based antivenoms.
But these antivenoms are expensive, and though they often save the victim’s life, they’re largely powerless against tissue death, or necrosis, around the snakebite wound. As a result, an estimated 400,000 people per year develop a permanent disability from a snakebite. In some cases, the affected limb must be amputated.
Now, researchers have discovered a possible solution to this problem: common blood thinners. In a new paper published last week in the journal Science Translational Medicine, an international team describes using heparin—a frequently prescribed and affordable blood thinner—and its related compounds to prevent cobra venom from killing tissue and cells.
“Cobra venoms cause profound local tissue damage … it’s like you’ve injected the person with acid,” says Bryan Fry, a biologist and biochemist at the University of Queensland in Australia who was not involved with the research, to the Guardian’s Sharlotte Thou. He adds that the new findings are “really exciting.”
Snakebites are a major issue in some parts of the world, killing between 81,000 and 138,000 people every year, especially in sub-Saharan Africa and South and Southeast Asia. The World Health Organization describes snakebite envenoming as a “neglected tropical disease” and has set a goal of halving the number of deaths and cases of permanent disability from snakebites by 2030.
But snake venom itself has long been mysterious. Since it’s made up of many different compounds, scientists have not been able to pinpoint exactly which component is responsible for causing necrosis in bite victims, writes Science’s Humberto Basilio. To try to solve this puzzle, the researchers turned to the gene-editing tool CRISPR—which also aided in the discovery of an antidote for box jellyfish venom five years ago.
The team studied how human cells react after being injected with venom from two African snake species: the red spitting cobra (Naja pallida) and the black-necked spitting cobra (Naja nigricollis). They noticed that toxins in the venom seemed to be binding with heparan sulfate and heparin, molecules produced by human cells that have a similar structure.
So, using CRISPR, they removed the genes responsible for producing heparan and heparin. Sure enough, when researchers injected the gene-edited cells with venom, the cells were more resilient against its effects.
The scientists wondered if injecting human cells with the blood thinner heparin and related heparinoids would essentially trick the toxins into binding with the medicine, rather than harming the cells. Testing this idea supported their hypothesis.
To verify these findings, they ran experiments involving mice. Injecting the rodents with heparinoids at the same time as the venom helped reduce the size of the animals’ resulting lesions. One drug, called tinzaparin, shrunk their wounds by 94 percent.
This method could also thwart the effects of venom from other cobras, including three species from Asia. However, the treatment did not work for all snake venoms—for example, it was ineffective against vipers. That’s because the primary compounds responsible for causing necrosis, known as three-finger toxins, are not present in all types of snake venom, per Science.
One unanswered question is whether antivenom would be just as effective at preventing necrosis if it could be administered immediately, rather than after an ambulance ride to a hospital, for instance. It’s also unclear how effective the blood thinners would be when more time has elapsed since the bite.
“Will it work after 1 hour, 4 hours or [the] 24 hours that it takes to get from a remote location in Tanzania to a person bitten by a cobra?” says Geoff Isbister, a clinical toxicologist at the University of Newcastle in Australia who was not involved with the research, to New Scientist’s James Woodford.
But the researchers say heparinoids are not intended to replace antivenom—rather, the treatments are meant to be complementary. Antivenoms still need to be injected to ensure the victim survives. But heparinoids—which are stable at room temperature and could be administered by an auto-injector, similar to an EpiPen—could be a stopgap for slowing down the venom until the patient can reach a hospital.
From here, heparinoids still need to go through clinical trials and be approved for human use against snakebites. But since these drugs are already approved and sold in pharmacies for other uses, the researchers expect the process to be relatively quick and easy.
“Heparin is inexpensive, ubiquitous and a World Health Organization-listed essential medicine,” says study co-author Tian Du, a neuroscientist and geneticist at the University of Sydney in Australia, in a statement. “After successful human trials, it could be rolled out relatively quickly to become a cheap, safe and effective drug for treating cobra bites.”
