Research ArticleBLEEDING

Affinity-based design of a synthetic universal reversal agent for heparin anticoagulants

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Science Translational Medicine  29 Oct 2014:
Vol. 6, Issue 260, pp. 260ra150
DOI: 10.1126/scitranslmed.3009427

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One Drug to Rule Them All

To clot or not to clot—that is the question. Prevention of blood clotting—anticoagulation—is preferred during surgical procedures or in blood vessels where clots can cause blockage. In fact, heparin-based anticoagulant drugs are used broadly for such purposes. But on the flip side, these anticoagulants are associated with bleeding risks that make close monitoring and neutralization necessary. Currently, only protamine has been clinically approved as an antidote to heparin-based anticoagulants; but the drug displays some adverse effects and is impotent against certain heparins and heparin-related medications. Now, Shenoi et al. describe a fully synthetic dendritic polymer–based universal heparin reversal agent (UHRA) that functions via multivalent presentation of branched cationic heparin binding groups (HBGs). The authors varied the agent’s scaffold, protective shell, and number and array of HBGs to develop an antidote that neutralized all clinically used heparin-related anticoagulants. The UHRA displayed safety and efficacy in animal models of heparin-induced bleeding. The new therapeutic may one day benefit patients in situations where the goal is to clot—such as in the treatment of excessive bleeding during anticoagulant therapy or high-risk surgery.