Research ArticleBlood clotting

Intravenous Hemostat: Nanotechnology to Halt Bleeding

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Science Translational Medicine  16 Dec 2009:
Vol. 1, Issue 11, pp. 11ra22
DOI: 10.1126/scitranslmed.3000397

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Editor's Summary

Basic first aid teaches us to put immediate pressure on a bleeding wound to stop the blood flow and allow natural clotting to occur. But what about when the wound is inside the body or difficult to compress? By coating polymer particles with peptides that promote platelet aggregation, Bertram et al. have made a synthetic “platelet” that accelerates natural platelet clotting and can be administered directly into the blood system to get access to internal organs. These tiny spheres can markedly decrease bleeding time in a rodent model with a serious injury to the femoral artery.

Because blood clotting is well understood, the authors knew to choose the peptide arginine-glycine-aspartic acid (RGD) to attach to ~600 ends of the polyethylene glycol arms that extended from their 170-nm polylysine spheres. RGD binds to receptors on the surface of activated platelets, so the particles with multiple RGDs specifically adhered to multiple platelets, facilitating their aggregation. The authors optimized other features of the nanoparticles to guarantee that they would be useful in the emergency room or on the battlefield. The materials used to make the particles have all been used in devices previously approved by the U.S. Food and Drug Administration. The small RGD peptide can be inexpensively synthesized, and its size makes it unlikely to cause immunological problems. When stored dry, the platelet-like nanoparticles are stable and remain effective for at least 2 weeks, far surpassing the 5- to 7-day shelf life of donated platelets. They are cleared from the system (in rats) within 24 hours.

To test how well these particles augmented blood clotting, the authors injected them into rats with a wound in the femoral artery. Whether the particles were injected before or, more realistically, after the wound was created, they reduced the bleeding time by 25% to 50%. Even the current standard of care for traumatic uncontrolled bleeding, a recombinant version of the natural clotting molecular factor VIIa, was less effective than the nanoparticles. Scanning electron micrographs of the blood clots from these treated rats confirmed that they contained numerous RGD-coated nanoparticles, nestled among blood cells, and a fibrin network.

These nanoparticles augment only one of the many functions of real platelets—injury-induced aggregation—but, in a traumatic situation, that could be the critical function that is needed.

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