Atypical antipsychotic clozapine binds fibrinogen and affects fibrin formation
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2020
Authors
Gligorijević, Nikola
Vasović, Tamara
Lević, Steva

Miljević, Cedo
Nedić, Olgica
Nikolić, Milan
Article (Published version)

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Clozapine is an atypical antipsychotic used for the treatment of schizophrenia. The prescribed target daily doses may reach 900mg. Literature studies report a connection between clozapine usage and thrombosis development. Our in vitro study aimed to provide insight into molecular bases of this observation, investigating clozapine binding to fibrinogen, the main plasma protein involved in hemostasis. Fibrinogen/clozapine interaction was confirmed by protein fluorescence quenching, with an affinity constant of 1.7 x 10(5) M-1. Direct interactions did not affect the structure of fibrinogen, nor fibrinogen melting temperature. Clozapine binding affected fibrin formation by reducing coagulation speed and thickness of fibrin fibers suggesting that in the presence of clozapine, fibrinogen may acquire thrombogenic characteristics. Although no difference in fibrin gel porosity was detected, other factors present in the blood may act synergistically with altered fibrin formation to modify fibrin... clot, thus increasing the risk for development of thrombosis in patients on clozapine treatment. ORAC and HORAC assays showed that clozapine reduced free radical-induced oxidation of fibrinogen. All observed effects of clozapine on fibrinogen are dose-dependent, with the effect on fibrin formation being more pronounced.
Keywords:
Fibrinogen / Clozapine / Binding / Thrombosis / Coagulation / HemostasisSource:
International Journal of Biological Macromolecules, 2020, 154, 142-149Publisher:
- Elsevier, Amsterdam
Funding / projects:
- Structural characterisation of the insulin-like growth factor (IGF) binding proteins and IGF receptors, their interactions with other physiological molecules and alterations in metabolic disorders (RS-173042)
- Rational design and synthesis of biologically active and coordination compounds and functional materials, relevant for (bio)nanotechnology (RS-172035)
DOI: 10.1016/j.ijbiomac.2020.03.119
ISSN: 0141-8130
PubMed: 32184141
WoS: 000533508600016
Scopus: 2-s2.0-85081672799
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Poljoprivredni fakultetTY - JOUR AU - Gligorijević, Nikola AU - Vasović, Tamara AU - Lević, Steva AU - Miljević, Cedo AU - Nedić, Olgica AU - Nikolić, Milan PY - 2020 UR - http://aspace.agrif.bg.ac.rs/handle/123456789/5370 AB - Clozapine is an atypical antipsychotic used for the treatment of schizophrenia. The prescribed target daily doses may reach 900mg. Literature studies report a connection between clozapine usage and thrombosis development. Our in vitro study aimed to provide insight into molecular bases of this observation, investigating clozapine binding to fibrinogen, the main plasma protein involved in hemostasis. Fibrinogen/clozapine interaction was confirmed by protein fluorescence quenching, with an affinity constant of 1.7 x 10(5) M-1. Direct interactions did not affect the structure of fibrinogen, nor fibrinogen melting temperature. Clozapine binding affected fibrin formation by reducing coagulation speed and thickness of fibrin fibers suggesting that in the presence of clozapine, fibrinogen may acquire thrombogenic characteristics. Although no difference in fibrin gel porosity was detected, other factors present in the blood may act synergistically with altered fibrin formation to modify fibrin clot, thus increasing the risk for development of thrombosis in patients on clozapine treatment. ORAC and HORAC assays showed that clozapine reduced free radical-induced oxidation of fibrinogen. All observed effects of clozapine on fibrinogen are dose-dependent, with the effect on fibrin formation being more pronounced. PB - Elsevier, Amsterdam T2 - International Journal of Biological Macromolecules T1 - Atypical antipsychotic clozapine binds fibrinogen and affects fibrin formation EP - 149 SP - 142 VL - 154 DO - 10.1016/j.ijbiomac.2020.03.119 ER -
@article{ author = "Gligorijević, Nikola and Vasović, Tamara and Lević, Steva and Miljević, Cedo and Nedić, Olgica and Nikolić, Milan", year = "2020", abstract = "Clozapine is an atypical antipsychotic used for the treatment of schizophrenia. The prescribed target daily doses may reach 900mg. Literature studies report a connection between clozapine usage and thrombosis development. Our in vitro study aimed to provide insight into molecular bases of this observation, investigating clozapine binding to fibrinogen, the main plasma protein involved in hemostasis. Fibrinogen/clozapine interaction was confirmed by protein fluorescence quenching, with an affinity constant of 1.7 x 10(5) M-1. Direct interactions did not affect the structure of fibrinogen, nor fibrinogen melting temperature. Clozapine binding affected fibrin formation by reducing coagulation speed and thickness of fibrin fibers suggesting that in the presence of clozapine, fibrinogen may acquire thrombogenic characteristics. Although no difference in fibrin gel porosity was detected, other factors present in the blood may act synergistically with altered fibrin formation to modify fibrin clot, thus increasing the risk for development of thrombosis in patients on clozapine treatment. ORAC and HORAC assays showed that clozapine reduced free radical-induced oxidation of fibrinogen. All observed effects of clozapine on fibrinogen are dose-dependent, with the effect on fibrin formation being more pronounced.", publisher = "Elsevier, Amsterdam", journal = "International Journal of Biological Macromolecules", title = "Atypical antipsychotic clozapine binds fibrinogen and affects fibrin formation", pages = "149-142", volume = "154", doi = "10.1016/j.ijbiomac.2020.03.119" }
Gligorijević, N., Vasović, T., Lević, S., Miljević, C., Nedić, O.,& Nikolić, M.. (2020). Atypical antipsychotic clozapine binds fibrinogen and affects fibrin formation. in International Journal of Biological Macromolecules Elsevier, Amsterdam., 154, 142-149. https://doi.org/10.1016/j.ijbiomac.2020.03.119
Gligorijević N, Vasović T, Lević S, Miljević C, Nedić O, Nikolić M. Atypical antipsychotic clozapine binds fibrinogen and affects fibrin formation. in International Journal of Biological Macromolecules. 2020;154:142-149. doi:10.1016/j.ijbiomac.2020.03.119 .
Gligorijević, Nikola, Vasović, Tamara, Lević, Steva, Miljević, Cedo, Nedić, Olgica, Nikolić, Milan, "Atypical antipsychotic clozapine binds fibrinogen and affects fibrin formation" in International Journal of Biological Macromolecules, 154 (2020):142-149, https://doi.org/10.1016/j.ijbiomac.2020.03.119 . .