New blood thinner prevents clots with less risk of excess bleeding

Photo by National Cancer Institute on Unsplash

We need our blood to walk a very fine line between flowing freely and clotting, and treatments for blood clots in the body naturally come with a risk of excessive bleeding from an injury. But now, researchers at EPFL have developed a synthetic blood thinner that doesn’t have this side effect, fighting thrombosis while still allowing blood to clot normally in a wound.

Blood clots in the bloodstream (thrombosis) can be extremely dangerous, particularly if they form in or travel to the brain, lungs or heart. Drugs called anticoagulants or “blood thinners” are often prescribed to break up these lumps, targeting enzymes that cause clots to form.

But there’s a clear downside to these. Blood clots perform the vital service of preventing us from bleeding out with every minor cut and scrape, so patients on blood thinners run the risk of excessive bleeding if they’re injured.

Now, researchers at EPFL have created the first synthetic blood thinner that prevents the formation of bad clots inside the body, while still letting them form to plug up wounds. The study has its roots in research from a few years ago, when scientists discovered the key to be an enzyme called coagulation factor XII (FXII). Mice genetically engineered to be deficient in this enzyme were found to have significantly reduced risk of thrombosis, while still allowing blood clots to form following an injury.

And now, the team has been the first to develop a synthetic molecule that can inhibit FXII to induce these beneficial effects. The team identified this particular peptide from a pool of a billion, then improved it by replacing several of its amino acids with synthetic versions.

The researchers tested the new drug in an artificial lung model and found that it efficiently reduced blood clotting without inducing extra bleeding.

“The new FXII inhibitor is a promising candidate for safe thromboprotection in artificial lungs, which are used to bridge the time between lung failure and lung transplantation,” says Christian Heinis, lead author of the study. “In these devices, contact of blood proteins with artificial surfaces such as the membrane of the oxygenator or tubing can cause blood clotting.”

In its current form, however, the team acknowledges that the molecule is too small, so the kidneys would filter it out quickly. To keep the benefits up for days or weeks at a time, patients would need constant infusions, which isn’t practical.

“We’re fixing this; we’re currently engineering variants of the FXII inhibitor with a longer retention time,” says Heinis.

Of course, this work is still in the very early stages, and hasn’t even been tested on animals yet, let alone humans. But it’s a promising and intriguing start to tackling a serious problem.

The research was published in the journal Nature Communications.

Source: EPFL

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