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Evaluation of CrataBL efficacy for reversal of heparinization

Grant number: 20/00360-0
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): August 01, 2020
Effective date (End): June 30, 2021
Field of knowledge:Biological Sciences - Biochemistry - Chemistry of Macromolecules
Principal Investigator:Maria Luiza Vilela Oliva
Grantee:Vinícius Goulart Nardelli
Home Institution: Instituto Nacional de Farmacologia (INFAR). Universidade Federal de São Paulo (UNIFESP). São Paulo , SP, Brazil
Associated research grant:17/06630-7 - Fragments derived from the structure of protease inhibitors with selectivity for inhibition of mammalian and microorganism enzymes and its role as an anti-inflammatory, antimicrobial, antithrombotic and anti- tumor agent: mechanism of action, AP.TEM

Abstract

Studies with the bifunctional protein CrataBL have shown that this protein prolongs the partially active thromboplastin test time (aPTT) by influencing the intrinsic coagulation pathway, and in addition it inhibits the effect of heparin on the same pathway suggesting that the interaction of CrataBL with Heparin neutralizes its anticoagulant effects. Contrary to the action of heparin, CrataBL did not influence either prothrombin time (PT) or thrombin time (TT), but impaired heparin-induced antithrombin III potentiation (1). These findings warrant the initiation of studies on the effects of CrataBL in experimental animal models of arterial thrombosis to evaluate its potential as a possible antithrombotic drug. Due to its inhibitory action on the anticoagulant effects of heparin, CrataBL is a possible alternative for antithrombotic treatment without causing bleeding. Another possible application involves reversing the anticoagulant effects of heparin in cases of excessive bleeding without causing too many side effects. (AU)