Synthetic Platelets Halve Clotting Time

Newly developed synthetic platelets made from biodegradable polymers show promise in halting internal and external bleeding.

Researchers at Case Western Reserve University (Cleveland, OH, USA) developed synthetic platelets based on an arginine, glycine, and aspartate (Arg-Gly-Asp) amino acid sequence that naturally resides in the cell attachment region of fibronectin, formed into functionalized nanoparticles. The synthetic platelets were designed to home in and link up with natural platelets which are activated by the injury, which then emit chemical factors that bind the natural platelets and the additional synthetics into a larger clot that quickly stems the bleeding. To avoid early formation of an artificial clot, each synthetic platelet was built with a surrounding water shield; the synthetic platelets not bound into clots are flushed from the blood system in a day.

In a rat model of major trauma to test the platelets, animals injected with the synthetic platelets prior to injury stopped bleeding in half the time of untreated models; and rats injected with the platelets 20 seconds after the injury stopped bleeding in 23% less time than models left untreated. In another comparison, the artificial platelets resulted in clotting times about 25% faster than wounds treated with recombinant factor VIIa, the current state of the art treatment for uncontrolled bleeding in surgery and emergency rooms (ERs). The synthetic platelets were cleared from the system within 24 hours at a dose of 20 mg/ml, and no complications were seen up to 7 days after infusion, the longest time point studied. The study was published in the December 16, 2009, issue of Science Translational Medicine.

"The reason we developed this synthetic platelet is that it is stable at all temperatures. It is a fine powder that can be administered intravenously. The faster you can control bleeding, the better the outcome,” said lead author biomedical engineering professor Erin Lavik, Ph.D. "These synthetic platelets may be useful for early intervention in trauma and demonstrate the role that nanotechnology can have in addressing unmet medical needs.”

Recombinant factor VIIa is a trypsin-like serine protease produced by Novo Nordisk (Copenhagen, Denmark). An initiator of thrombin generation, factor VIIa acts primarily via two pathways to activate Factor Xa. One pathway is at the site of tissue injury in a complex with tissue factor, and the other is on the surface of platelets, independent of tissue factor. Theoretically, both of these mechanisms localize the action of factor VIIa to the site of injury, and hence avoid the complications of thromboses occurring in other vascular beds and leading to Acute Respiratory Distress Syndrome (ARDS), acute renal failure, and multiple organ dysfunction syndrome.

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