Dextran-based materials reducing anticoagulant activity of heparin in animal models in vitro and in vivo
|Kamil K. Kamiński 1, Krzysztof Szczubiałka 1, Maria Nowakowska 1, Bartłomiej Kalaska 2, Emilia Sokołowska 2, Andrzej Mogielnicki 2, Włodzimierz Buczko 2|
1. Jagiellonian University, Faculty of Chemistry, Ingardena 3, Kraków 30-060, Poland
Heparin is a naturally occurring polysaccharide used in many medical applications, especially for treating cardiovascular diseases . This polymer has a natural ability to prevent blood clot formation in mammals both in vitro and in vivo. Anticoagulative effect of heparin is often difficult to predict and in the case of an emergency (e.g. haemorrhage due to the heparin overdose) it has to be reduced. The only substance currently used in such situations is protamine sulphate (PS). This protein, however, can be a cause of many adverse effects, e.g. life threatening allergic response  or hypotension. Therefore, there is a necessity of developing a safer alternative which could replace it.
Figure 1. Dependence of activated thromboplastin time (aPTT) on the applied dose of the polymer
The reversal of heparin action by DeX-GTMAC was clearly seen in the mice developing chemically induced venous thrombosis and was even more potent than the effect of PS. Both DeX-GTMAC and PS reversed the prolongation of bleeding time and aPTT by heparin administered in rats and mice. Moreover, other routinely measured blood parameters are significantly affected. DeX-GTMAC, in contrast to the PS, significantly increase red blood cell counts, hemoglobin level and haematocrit value. The data obtained show that the cationically-modified dextran may be potentially used to reverse anticoagulative heparin activity.
Acknowledgement: The project was operated within the Fundation for Polish Science Team Programme (TEAM/2008-2/6) and Ventures Programme (Ventures/2009-4/4) cofinanced by EU European Regional Development Fund
Presentation: Oral at VIII Multidyscyplinarna Konferencja Nauki o Leku, by Kamil K. Kamiński
See On-line Journal of VIII Multidyscyplinarna Konferencja Nauki o Leku
Submitted: 2012-02-26 16:44 Revised: 2012-02-28 10:52
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