B. Kalaska, E. Sokolowska, K. Kaminski, J. Miklosz, Y. Shin-ichi, A. Błazejczyk, J. Wietrzyk, I. Kasacka, K. Szczubialka, D. Pawlak, M. Nowakowska, A. Mogielnicki
Medical University of Bialystok, Poland
pp. 278 - 280
Keywords: heparin, antidote, polymer, thrombosis, coagulation, animal model
The incredible progress and wide use of various medical devices during intravascular or cardiac interventions increased the need for administration of anticoagulants, such as heparins. Protamine sulfate – a protein isolated from salmons is the only one registered antidote of heparin. It is widely used to restore blood coagulation in case of severe bleedings related to heparin therapy. However, around one thousand deaths a year in US could be attributed to complications after protamine injection; mostly because of its allergic properties. We synthesized group of cationic polymers able to bind heparin in blood. One of the heparin-binding copolymers (HBC) efficiently neutralized heparin activity in the living animal. HBC1 injected intravenously 3 minutes after heparin, restored thrombus development, bleeding, clotting, and activity of coagulation factors to normal values. When administered in the therapeutic doses, HBC1 did not influence blood count and chemistry, platelets activity, cardiovascular and respiratory functions of rat. Intravital imaging revealed rapid elimination of polymer with urine. In conclusion HBC1 is efficient, safe and easy to synthesize polymer, that could replace protamine for the treatment of heparin associated bleeding. Our technology presents a pharmaceutical companies a unique opportunity to optimize a lead compound into a marketable therapeutic.