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Polymer can stop lethal bleeding in vivo


 

Rendering of fibrin forming

a blood clot, with PolySTAT

(blue) binding strands together

Image by William Walker–

University of Washington

Preclinical research suggests an injectable polymer known as PolySTAT may one day be able to halt life-threatening bleeding in soldiers and trauma patients.

Once injected, this hemostatic polymer circulates in the blood, homes to sites of vascular injury, and promotes the formation of blood clots.

In experiments with rats, 100% of animals injected with PolySTAT survived a typically lethal injury to the femoral artery. In comparison, 0% to 40% of controls survived.

“Most of the patients who die from bleeding die quickly,” said Nathan White, MD, of the University of Washington in Seattle.

“[PolySTAT] is something you could potentially put in a syringe inside a backpack and give right away to reduce blood loss and keep people alive long enough to make it to medical care.”

Dr White and his colleagues described their work with PolySTAT in Science Translational Medicine. A related Focus article addressed the promises and challenges of advancing PolySTAT and other clotting approaches from proof-of-principle to clinical development.

PolySTAT induces hemostasis by cross-linking the fibrin matrix within blood clots, just as factor XIII does. But the researchers said PolySTAT offers greater protection against natural enzymes that dissolve blood clots.

That’s because PolySTAT binds to fibrin monomers and is uniformly integrated into fibrin fibers during polymerization. This produces a fortified, hybrid polymer network that can resist enzymatic degradation.

In vitro experiments showed that PolySTAT accelerated clotting kinetics, increased the strength of blood clots, and delayed clot breakdown.

The researchers also assessed how PolySTAT affected rats following a femoral artery injury, comparing results with PolySTAT to those with volume control (0.9% saline), a nonbinding scrambled control polymer (PolySCRAM), rat albumin, and human FXIIIa.

The team found that PolySTAT conferred superior survival by reducing blood loss and fluid resuscitation requirements.

All of the rats treated with PolySTAT (5/5) survived to the end of the experiment, compared to none of the rats that received albumin, 20% that received PolySCRAM or FXIIIa, and 40% that received volume control.

The researchers said PolySTAT’s initial safety profile looks promising, but they are still planning to test the polymer on larger animals and conduct additional screening to find out if PolySTAT binds to any other unintended substances.

The team also plans to investigate PolySTAT’s potential for treating hemophilia and for integration into bandages.

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