In the paper published in Biomacromolecules, 1 Dr. Also, UHRA can reverse all the clinically used heparins. Compared to protamine, UHRA can be used in a wide range of doses and is highly biocompatible. UHRA has two major structural components: a hyperbranched polyglycerol core decorated with positive charges and a brush layer of methoxypolyethylene glycol (mPEG) chains (Figure 1). The Kizhakkedathu and Haynes labs have previously developed a superior antidote to heparins called Universal Heparin Reversal Agent (UHRA). Secondly, protamine is only able to completely neutralize unfractionated heparin (UFH) it has a moderate antidote activity towards low molecular weight heparins (LMWHs) and no activity against Fondaparinux. At higher doses, protamine binds non-specifically to blood proteins and shows some anticoagulant effects. Firstly, it has only a small range of doses where it can effectively neutralize heparins.

Protamine is a positively charged peptide that binds to negatively charged heparin via electrostatic interactions. The only FDA approved heparin antidote is protamine sulphate (protamine). Hence, it is important to be able to neutralize heparins. Although heparins are effective in preventing blood clots, the risk of bleeding associated with their use is a major clinical concern. In spite of the introduction of anti-Xa and anti-thrombin agents to treat/prevent thrombosis, heparin continues to be used in major surgeries like cardio-pulmonary bypass to prevent blood clotting. They were the primary agents used to treat deep vein thrombosis, arterial thromboembolism, and ischemic stroke. Historically, heparins were the mainstay of anticoagulant therapy. By Sreeparna Vappala, Graduate Student, Kizhakkedathu Lab

Antidote to heparin