Bloodstream Scavengers Inhibit Clotting Without Triggering Hemorrhage

A new study describes a compound that clears the debris of damaged cells from the bloodstream, stopping the formation of blood clots without eliciting bleeding.

Researchers at Duke University Medical Center (Duke, Durham, NC, USA) conducted a study to evaluate the anticoagulant and antithrombotic activity of compounds known as nucleic acid-binding polymers (NABPs). They found that the polymers bind to DNA, RNA, and inorganic polyphosphate molecules with high affinity, and inhibit RNA- and polyphosphate-induced clotting and the activation of the intrinsic pathway of coagulation in vitro. In test tube-based assays and experiments in two mouse models, the NABPs proved to be potent inhibitors of thrombosis, without simultaneously triggering abnormal bleeding.

Moreover, one of the polymers, called PAMAM G-3, prevented thrombosis following carotid artery injury and pulmonary thromboembolism in the mice, without significantly increasing blood loss from surgically challenged animals, and with reduced toxicity. According to the researchers, NABPs could represent a new and potentially safer class of antithrombotic agents. The study builds upon a previous research that found NABPs also have the potential to interrupt the inflammatory response, a hallmark of autoimmune disorders such as lupus and multiple sclerosis (MS). The study was published online on July 23, 2012, in the Proceedings of the National Academy of Sciences of the USA (PNAS).

“In the thrombosis (clotting) space, the holy grail has been to make something antithrombotic that doesn't significantly increase your chance of hemorrhage or bleeding,” said senior author Bruce Sullenger, PhD, director of the Duke Translational Research Institute. “We think this is a promising example of a type of compound that could do that. If it can be clinically developed and exhibit the same properties in humans, clearly that would improve safety and outcome of treating patients who have thrombotic disease.”

Dying and diseased cells spill rogue sections of DNA and RNA into the bloodstream, high levels of nucleic acids remnants that trigger an inflammatory immune response, as well as triggering the coagulation response.

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