’Overall, I would say this is an interesting approach but with a long way to go to prove itself as a protamine alternative,’ says Bob Linhardt, a heparin expert at the Rensselaer Polytechnic Institute in New York, US. A blood clot is a gel-like collection of blood in your veins or arteries. Smith is already working on this to see whether biological fluids interfere with binding. Heparin is an anticoagulant (blood thinner) that prevents blood clots. and is expected to bio-degrade to innocuous products, thereby functioning under in vivo conditions in a more predictable and less noxious manner,’ says Umesh Desai, a medicinal chemist at Virginia Commonwealth University in the US.ĭesai and other chemists say the molecule should have been tested in blood or plasma, where its effectiveness - and toxicity - may be different. Approximately 1 mg of protamine sulphate neutralizes 100 iu of heparin. ’The interesting aspect of this work is that the designed heparin antidote is much smaller at a molecular level. The effects of heparin can be reversed by protamine sulphate. Indeed, during in vitro tests in salt solutions, the protamine alternative was ’directly comparable to, if not a little bit better than, protamine,’ says Smith. These nanostructures have branches of positive charge to aid binding to heparin. The molecules developed by Smith’s group contain hydrophobic units that self-assemble in water into spherical nanostructures of a similar size to protamine. Protamine sulfate partially reverses the anticoagulant effect of LMWH and may prevent bleeding from LMWH overdose. Now, however, David Smith and colleagues at the University of York have developed heparin binders that only temporarily become positively charged, so the risk of an allergic reaction is reduced. Heparin can be neutral-ized by protamine, and warfarin anticoagulation can be reversed by vitamin K injections. Bleeding in low-molecular-weight heparin (LMWH) overdose is unpredictable and may develop insidiously in deep tissues such as retroperitoneal and intramuscular spaces. But positively charged polymers are often toxic, and these alternatives have proved unsuitable for clinical use.

Heparin is negatively charged, so the protamine alternatives developed so far have mostly been positively charged, like protamine itself. New molecule can bind heparin, counteracting its effects

Antidote to heparin