TY  - JOUR
AU  - Cumbo, Marija
AU  - Dunjić-Manevski, Sofija
AU  - Gvozdenov, Maja
AU  - Mitić, Martina Mia
AU  - Đorđević, Valentina
AU  - Tomić, Branko
PY  - 2024
UR  - https://doiserbia.nb.rs/Article.aspx?ID=0354-46642400007C
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2358
AB  - Thrombotic disorders are some of the main comorbidities in cancer patients. So far, research has indicated that thrombin, a key regulator of hemostasis, contributes to cancer progression. However, data on its origin in tumor microenvironments remain elusive. Based on previous research, we analyzed the RNA and protein expression of prothrombin, a precursor of thrombin, in selected colorectal cancer (CRC) cell lines. Since the effect of prothrombin in cancer development has not been previously reported, we treated the cells for 24 h and 48 h with different prothrombin concentrations and assessed the effect on cell proliferation and migration. Our results show that the tested CRC cell lines expressed prothrombin and that prothrombin inhibited proliferation and migration. The presented results suggest that prothrombin may contribute to CRC etiopathology and could serve as a potential diagnostic biomarker and therapeutic target. The mechanisms underlying prothrombin expression in cancer cells, potential prothrombin activation, and the underlying processes driving the described effects warrant further investigation.
PB  - Serbian Biological Society, Institute for Biological Research "Siniša Stanković"
T2  - Archives of Biological Sciences
T2  - Archives of Biological Sciences
T1  - The effect of prothrombin, the precursor of thrombin, on the proliferation and migration of colorectal cancer cells
EP  - 120
IS  - 1
SP  - 111
VL  - 76
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2358
ER  - 

@article{
author = "Cumbo, Marija and Dunjić-Manevski, Sofija and Gvozdenov, Maja and Mitić, Martina Mia and Đorđević, Valentina and Tomić, Branko",
year = "2024",
abstract = "Thrombotic disorders are some of the main comorbidities in cancer patients. So far, research has indicated that thrombin, a key regulator of hemostasis, contributes to cancer progression. However, data on its origin in tumor microenvironments remain elusive. Based on previous research, we analyzed the RNA and protein expression of prothrombin, a precursor of thrombin, in selected colorectal cancer (CRC) cell lines. Since the effect of prothrombin in cancer development has not been previously reported, we treated the cells for 24 h and 48 h with different prothrombin concentrations and assessed the effect on cell proliferation and migration. Our results show that the tested CRC cell lines expressed prothrombin and that prothrombin inhibited proliferation and migration. The presented results suggest that prothrombin may contribute to CRC etiopathology and could serve as a potential diagnostic biomarker and therapeutic target. The mechanisms underlying prothrombin expression in cancer cells, potential prothrombin activation, and the underlying processes driving the described effects warrant further investigation.",
publisher = "Serbian Biological Society, Institute for Biological Research "Siniša Stanković"",
journal = "Archives of Biological Sciences, Archives of Biological Sciences",
title = "The effect of prothrombin, the precursor of thrombin, on the proliferation and migration of colorectal cancer cells",
pages = "120-111",
number = "1",
volume = "76",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2358"
}

Cumbo, M., Dunjić-Manevski, S., Gvozdenov, M., Mitić, M. M., Đorđević, V.,& Tomić, B.. (2024). The effect of prothrombin, the precursor of thrombin, on the proliferation and migration of colorectal cancer cells. in Archives of Biological Sciences
Serbian Biological Society, Institute for Biological Research "Siniša Stanković"., 76(1), 111-120.
https://hdl.handle.net/21.15107/rcub_imagine_2358

Cumbo M, Dunjić-Manevski S, Gvozdenov M, Mitić MM, Đorđević V, Tomić B. The effect of prothrombin, the precursor of thrombin, on the proliferation and migration of colorectal cancer cells. in Archives of Biological Sciences. 2024;76(1):111-120.
https://hdl.handle.net/21.15107/rcub_imagine_2358 .

Cumbo, Marija, Dunjić-Manevski, Sofija, Gvozdenov, Maja, Mitić, Martina Mia, Đorđević, Valentina, Tomić, Branko, "The effect of prothrombin, the precursor of thrombin, on the proliferation and migration of colorectal cancer cells" in Archives of Biological Sciences, 76, no. 1 (2024):111-120,
https://hdl.handle.net/21.15107/rcub_imagine_2358 .

TY  - JOUR
AU  - Kovac, Mirjana
AU  - Balint, Milena Todorovic
AU  - Milenković, Marija
AU  - Basaric, Dušica
AU  - Tomić, Branko
AU  - Balint, Bela
AU  - Ignjatović, Vera
PY  - 2024
UR  - http://www.thieme-connect.de/DOI/DOI?10.1055/a-2238-4744
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2329
AB  - Changes in the hemostatic system during COVID infection lead to hypercoagulability. Numerous studies have evaluated hemostatic abnormalities in COVID patients during acute infection, in the period of hospitalization. However, the hemostatic status following hospital discharge has not been sufficiently assessed. Considering the importance of FVIII and D-dimer levels as markers for the assessment of thrombosis, our study aimed to evaluate changes in these markers, as well as the influence of patient's age and clinical presentation of COVID infection on those hemostatic markers in the post-COVID phase. This prospective study (July 2020 to December 2022) included 115 COVID patients, 68 (59%) with asymptomatic/mild and 47 (41%) with moderate/severe clinical presentation. Patient follow-up included laboratory evaluation of FVIII and D-dimer levels at 1, 3, and 6 months following the COVID infection. Three months after the COVID infection, elevated FVIII was recorded in 44% of younger versus 65% of older individuals, p = 0.05, respectively, and 30 versus 57% (p = 0.008) 6 months post–COVID infection. With a focus on clinical presentation, a higher number of patients with moderate/severe COVID had elevated FVIII activity, but a statistically significant difference was observed only for the 6 months (32% mild vs. 53% moderate/severe, p = 0.041) post-infection time point. Following a COVID infection, an increase in FVIII activity suggests a continued hypercoagulable state in the post-COVID period and correlates with elevated D-dimer levels. This increase in FVIII is more pronounced in patients with moderate/severe clinical picture and those patients older than 50 years.
PB  - Georg Thieme Verlag KG
T2  - Hämostaseologie
T1  - Assessment of Factor VIII Activity and D-Dimer Levels in the Post-COVID Period
DO  - 10.1055/a-2238-4744
ER  - 

@article{
author = "Kovac, Mirjana and Balint, Milena Todorovic and Milenković, Marija and Basaric, Dušica and Tomić, Branko and Balint, Bela and Ignjatović, Vera",
year = "2024",
abstract = "Changes in the hemostatic system during COVID infection lead to hypercoagulability. Numerous studies have evaluated hemostatic abnormalities in COVID patients during acute infection, in the period of hospitalization. However, the hemostatic status following hospital discharge has not been sufficiently assessed. Considering the importance of FVIII and D-dimer levels as markers for the assessment of thrombosis, our study aimed to evaluate changes in these markers, as well as the influence of patient's age and clinical presentation of COVID infection on those hemostatic markers in the post-COVID phase. This prospective study (July 2020 to December 2022) included 115 COVID patients, 68 (59%) with asymptomatic/mild and 47 (41%) with moderate/severe clinical presentation. Patient follow-up included laboratory evaluation of FVIII and D-dimer levels at 1, 3, and 6 months following the COVID infection. Three months after the COVID infection, elevated FVIII was recorded in 44% of younger versus 65% of older individuals, p = 0.05, respectively, and 30 versus 57% (p = 0.008) 6 months post–COVID infection. With a focus on clinical presentation, a higher number of patients with moderate/severe COVID had elevated FVIII activity, but a statistically significant difference was observed only for the 6 months (32% mild vs. 53% moderate/severe, p = 0.041) post-infection time point. Following a COVID infection, an increase in FVIII activity suggests a continued hypercoagulable state in the post-COVID period and correlates with elevated D-dimer levels. This increase in FVIII is more pronounced in patients with moderate/severe clinical picture and those patients older than 50 years.",
publisher = "Georg Thieme Verlag KG",
journal = "Hämostaseologie",
title = "Assessment of Factor VIII Activity and D-Dimer Levels in the Post-COVID Period",
doi = "10.1055/a-2238-4744"
}

Kovac, M., Balint, M. T., Milenković, M., Basaric, D., Tomić, B., Balint, B.,& Ignjatović, V.. (2024). Assessment of Factor VIII Activity and D-Dimer Levels in the Post-COVID Period. in Hämostaseologie
Georg Thieme Verlag KG..
https://doi.org/10.1055/a-2238-4744

Kovac M, Balint MT, Milenković M, Basaric D, Tomić B, Balint B, Ignjatović V. Assessment of Factor VIII Activity and D-Dimer Levels in the Post-COVID Period. in Hämostaseologie. 2024;.
doi:10.1055/a-2238-4744 .

Kovac, Mirjana, Balint, Milena Todorovic, Milenković, Marija, Basaric, Dušica, Tomić, Branko, Balint, Bela, Ignjatović, Vera, "Assessment of Factor VIII Activity and D-Dimer Levels in the Post-COVID Period" in Hämostaseologie (2024),
https://doi.org/10.1055/a-2238-4744 . .

TY  - JOUR
AU  - Dunjić Manevski, Sofija
AU  - Cumbo, Marija
AU  - Pruner, Iva
AU  - Gvozdenov, Maja
AU  - Tomić, Branko
AU  - Taxiarchis, Apostolos
AU  - Antović, Jovan
AU  - Đordjević, Valentina
PY  - 2023
UR  - https://onlinelibrary.wiley.com/doi/abs/10.1111/ijlh.14195
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2199
AB  - Introduction Prothrombin Belgrade mutation is the result of the c.1787G>A substitution in the prothrombin gene. It is located in the antithrombin and sodium binding site and leads to impaired inactivation of thrombin by antithrombin, resulting in antithrombin resistance and thrombotic disorders. However, it negatively affects sodium binding and may have hypocoagulant effects. Considering that prothrombin Belgrade mutation mechanism is still not fully elucidated and that sodium binding is important for thrombin affinity towards fibrinogen, our aim was to determine whether this mutation affects fibrin clot formation and lysis. Methods Using HEK293T cell line, recombinant wild type and mutated prothrombin were generated by transient transfection. Samples that correspond to plasma of a non-carrier, heterozygous and homozygous carriers were reconstituted using prothrombin deficient plasma and recombinant proteins. Reconstituted samples were used in OHP assay (Overall Hemostasis Potential) to determine kinetic profiles of coagulation and fibrinolysis. Clot turbidity assay was performed to observe kinetics of clot formation and lysis more closely. Fibrin clots formed in reconstituted plasma samples were analyzed by confocal microscopy to determine density of fibrin network. Fibrin clots were additionally observed using electron microscopy to determine thickness of individual fibrin fibers. Results No significant difference found in OHP, OCP, OFP, and fibrin network density between wild type, heterozygous, and homozygous carrier reconstituted plasma samples. There were significant differences between samples for slope and slope time parameters in kinetic profiles and fibrin fiber thickness. Conclusions Results indicate that prothrombin Belgrade mutation has no significant impact on fibrinolysis, however it may affect kinetics of clot formation and its architecture.
T2  - International Journal of Laboratory Hematology
T1  - Effect of prothrombin Belgrade mutation, causing antithrombin resistance, on fibrin clot properties
VL  - n/a
DO  - 10.1111/ijlh.14195
ER  - 

@article{
author = "Dunjić Manevski, Sofija and Cumbo, Marija and Pruner, Iva and Gvozdenov, Maja and Tomić, Branko and Taxiarchis, Apostolos and Antović, Jovan and Đordjević, Valentina",
year = "2023",
abstract = "Introduction Prothrombin Belgrade mutation is the result of the c.1787G>A substitution in the prothrombin gene. It is located in the antithrombin and sodium binding site and leads to impaired inactivation of thrombin by antithrombin, resulting in antithrombin resistance and thrombotic disorders. However, it negatively affects sodium binding and may have hypocoagulant effects. Considering that prothrombin Belgrade mutation mechanism is still not fully elucidated and that sodium binding is important for thrombin affinity towards fibrinogen, our aim was to determine whether this mutation affects fibrin clot formation and lysis. Methods Using HEK293T cell line, recombinant wild type and mutated prothrombin were generated by transient transfection. Samples that correspond to plasma of a non-carrier, heterozygous and homozygous carriers were reconstituted using prothrombin deficient plasma and recombinant proteins. Reconstituted samples were used in OHP assay (Overall Hemostasis Potential) to determine kinetic profiles of coagulation and fibrinolysis. Clot turbidity assay was performed to observe kinetics of clot formation and lysis more closely. Fibrin clots formed in reconstituted plasma samples were analyzed by confocal microscopy to determine density of fibrin network. Fibrin clots were additionally observed using electron microscopy to determine thickness of individual fibrin fibers. Results No significant difference found in OHP, OCP, OFP, and fibrin network density between wild type, heterozygous, and homozygous carrier reconstituted plasma samples. There were significant differences between samples for slope and slope time parameters in kinetic profiles and fibrin fiber thickness. Conclusions Results indicate that prothrombin Belgrade mutation has no significant impact on fibrinolysis, however it may affect kinetics of clot formation and its architecture.",
journal = "International Journal of Laboratory Hematology",
title = "Effect of prothrombin Belgrade mutation, causing antithrombin resistance, on fibrin clot properties",
volume = "n/a",
doi = "10.1111/ijlh.14195"
}

Dunjić Manevski, S., Cumbo, M., Pruner, I., Gvozdenov, M., Tomić, B., Taxiarchis, A., Antović, J.,& Đordjević, V.. (2023). Effect of prothrombin Belgrade mutation, causing antithrombin resistance, on fibrin clot properties. in International Journal of Laboratory Hematology, n/a.
https://doi.org/10.1111/ijlh.14195

Dunjić Manevski S, Cumbo M, Pruner I, Gvozdenov M, Tomić B, Taxiarchis A, Antović J, Đordjević V. Effect of prothrombin Belgrade mutation, causing antithrombin resistance, on fibrin clot properties. in International Journal of Laboratory Hematology. 2023;n/a.
doi:10.1111/ijlh.14195 .

Dunjić Manevski, Sofija, Cumbo, Marija, Pruner, Iva, Gvozdenov, Maja, Tomić, Branko, Taxiarchis, Apostolos, Antović, Jovan, Đordjević, Valentina, "Effect of prothrombin Belgrade mutation, causing antithrombin resistance, on fibrin clot properties" in International Journal of Laboratory Hematology, n/a (2023),
https://doi.org/10.1111/ijlh.14195 . .

TY  - CONF
AU  - Dunjić Manevski, Sofija
AU  - Cumbo, Marija
AU  - Gvozdenov, Maja
AU  - Tomić, Branko
AU  - Ušjak, Dušan
AU  - Đorđević
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2126
AB  - Introduction: The prothrombin Belgrade variant (c.1787G>A, p.Arg596Gln) is a rare mutation found in
Serbia, Japan, China, America, India and leads to antithrombin resistance. Prothrombin Belgrade mutation influencesthrombin-antithrombin interactions and leadsto impaired inactivation of mutated thrombin. Also, it affectssodium binding site in thrombin, which isimportant forswitching from fast thrombin
configuration (coagulant properties) to slow configuration (anticoagulant properties). It has only been
found in a heterozygous state, which could mean that homozygous carriers are incompatible with life.
By using prothrombin (FII) deficient plasma, we could reconstitute plasma of wild type, heterozygous and
homozygous carrier, which could give more insight into the mechanism of this mutation.
Methods: Recombinant wild type and mutated prothrombin were generated by transient transfection
in HEK293T cell line. Western blot analysis was performed to test the efficiency of transfection. Human
Prothrombin ELISA (Nordic BioSite, Sweden) was used in order to measure recombinant prothrombin
concentration. Overall Hemostasis Potential (OHP) assay was performed to assess recombinant protein
activity. Recombinant wild type and mutated prothrombin were added to FII deficient plasma (Siemens,
Germany) in order to create reconstituted plasma, in the final concentration of 0.1 mg/mL, as it is approximately the level of prothrombin in human plasma.
Results: Reconstituted plasma samples that correspond to non-carrier, heterozygous carrier, and homozygous mutation carrier plasma were reconstructed. Recombinant proteinstested by OHP assay were
functional.
Conclusion: Reconstituted plasma samples allow us to examine the mechanism of prothrombin Belgrade mutation in various assays and in homozygous form as well.
PB  - Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade
C3  - CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia
T1  - Reconstitution of non-carrier, heterozygous and homozygous prothrombin belgrade mutation carrier plasma using recombinant proteins
EP  - 71
SP  - 71
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2126
ER  - 

@conference{
author = "Dunjić Manevski, Sofija and Cumbo, Marija and Gvozdenov, Maja and Tomić, Branko and Ušjak, Dušan and Đorđević",
year = "2023",
abstract = "Introduction: The prothrombin Belgrade variant (c.1787G>A, p.Arg596Gln) is a rare mutation found in
Serbia, Japan, China, America, India and leads to antithrombin resistance. Prothrombin Belgrade mutation influencesthrombin-antithrombin interactions and leadsto impaired inactivation of mutated thrombin. Also, it affectssodium binding site in thrombin, which isimportant forswitching from fast thrombin
configuration (coagulant properties) to slow configuration (anticoagulant properties). It has only been
found in a heterozygous state, which could mean that homozygous carriers are incompatible with life.
By using prothrombin (FII) deficient plasma, we could reconstitute plasma of wild type, heterozygous and
homozygous carrier, which could give more insight into the mechanism of this mutation.
Methods: Recombinant wild type and mutated prothrombin were generated by transient transfection
in HEK293T cell line. Western blot analysis was performed to test the efficiency of transfection. Human
Prothrombin ELISA (Nordic BioSite, Sweden) was used in order to measure recombinant prothrombin
concentration. Overall Hemostasis Potential (OHP) assay was performed to assess recombinant protein
activity. Recombinant wild type and mutated prothrombin were added to FII deficient plasma (Siemens,
Germany) in order to create reconstituted plasma, in the final concentration of 0.1 mg/mL, as it is approximately the level of prothrombin in human plasma.
Results: Reconstituted plasma samples that correspond to non-carrier, heterozygous carrier, and homozygous mutation carrier plasma were reconstructed. Recombinant proteinstested by OHP assay were
functional.
Conclusion: Reconstituted plasma samples allow us to examine the mechanism of prothrombin Belgrade mutation in various assays and in homozygous form as well.",
publisher = "Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade",
journal = "CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia",
title = "Reconstitution of non-carrier, heterozygous and homozygous prothrombin belgrade mutation carrier plasma using recombinant proteins",
pages = "71-71",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2126"
}

Dunjić Manevski, S., Cumbo, M., Gvozdenov, M., Tomić, B., Ušjak, D.,& Đorđević. (2023). Reconstitution of non-carrier, heterozygous and homozygous prothrombin belgrade mutation carrier plasma using recombinant proteins. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia
Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade., 71-71.
https://hdl.handle.net/21.15107/rcub_imagine_2126

Dunjić Manevski S, Cumbo M, Gvozdenov M, Tomić B, Ušjak D, Đorđević. Reconstitution of non-carrier, heterozygous and homozygous prothrombin belgrade mutation carrier plasma using recombinant proteins. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia. 2023;:71-71.
https://hdl.handle.net/21.15107/rcub_imagine_2126 .

Dunjić Manevski, Sofija, Cumbo, Marija, Gvozdenov, Maja, Tomić, Branko, Ušjak, Dušan, Đorđević, "Reconstitution of non-carrier, heterozygous and homozygous prothrombin belgrade mutation carrier plasma using recombinant proteins" in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia (2023):71-71,
https://hdl.handle.net/21.15107/rcub_imagine_2126 .

TY  - CONF
AU  - Dunjić Manevski, Sofija
AU  - Cumbo, Marija
AU  - Gvozdenov, Maja
AU  - Tomić, Branko
AU  - Ušjak, Dušan
AU  - Đorđević, Valentina
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2123
AB  - Introduction: The prothrombin Belgrade variant (c.1787G>A, p.Arg596Gln) is a rare mutation found in
Serbia, Japan, China, America, India and leads to antithrombin resistance. Prothrombin Belgrade mutation influencesthrombin-antithrombin interactions and leadsto impaired inactivation of mutated thrombin. Also, it affectssodium binding site in thrombin, which isimportant forswitching from fast thrombin
configuration (coagulant properties) to slow configuration (anticoagulant properties). It has only been
found in a heterozygous state, which could mean that homozygous carriers are incompatible with life.
By using prothrombin (FII) deficient plasma, we could reconstitute plasma of wild type, heterozygous and
homozygous carrier, which could give more insight into the mechanism of this mutation.
Methods: Recombinant wild type and mutated prothrombin were generated by transient transfection
in HEK293T cell line. Western blot analysis was performed to test the efficiency of transfection. Human
Prothrombin ELISA (Nordic BioSite, Sweden) was used in order to measure recombinant prothrombin
concentration. Overall Hemostasis Potential (OHP) assay was performed to assess recombinant protein
activity. Recombinant wild type and mutated prothrombin were added to FII deficient plasma (Siemens,
Germany) in order to create reconstituted plasma, in the final concentration of 0.1 mg/mL, as it is approximately the level of prothrombin in human plasma.
Results: Reconstituted plasma samples that correspond to non-carrier, heterozygous carrier, and homozygous mutation carrier plasma were reconstructed. Recombinant proteinstested by OHP assay were
functional.
Conclusion: Reconstituted plasma samples allow us to examine the mechanism of prothrombin Belgrade mutation in various assays and in homozygous form as well.
PB  - Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade
C3  - CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia
T1  - Reconstitution of non-carrier, heterozygous and homozygous prothrombin belgrade mutation carrier plasma using recombinant proteins
EP  - 71
SP  - 71
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2123
ER  - 

@conference{
author = "Dunjić Manevski, Sofija and Cumbo, Marija and Gvozdenov, Maja and Tomić, Branko and Ušjak, Dušan and Đorđević, Valentina",
year = "2023",
abstract = "Introduction: The prothrombin Belgrade variant (c.1787G>A, p.Arg596Gln) is a rare mutation found in
Serbia, Japan, China, America, India and leads to antithrombin resistance. Prothrombin Belgrade mutation influencesthrombin-antithrombin interactions and leadsto impaired inactivation of mutated thrombin. Also, it affectssodium binding site in thrombin, which isimportant forswitching from fast thrombin
configuration (coagulant properties) to slow configuration (anticoagulant properties). It has only been
found in a heterozygous state, which could mean that homozygous carriers are incompatible with life.
By using prothrombin (FII) deficient plasma, we could reconstitute plasma of wild type, heterozygous and
homozygous carrier, which could give more insight into the mechanism of this mutation.
Methods: Recombinant wild type and mutated prothrombin were generated by transient transfection
in HEK293T cell line. Western blot analysis was performed to test the efficiency of transfection. Human
Prothrombin ELISA (Nordic BioSite, Sweden) was used in order to measure recombinant prothrombin
concentration. Overall Hemostasis Potential (OHP) assay was performed to assess recombinant protein
activity. Recombinant wild type and mutated prothrombin were added to FII deficient plasma (Siemens,
Germany) in order to create reconstituted plasma, in the final concentration of 0.1 mg/mL, as it is approximately the level of prothrombin in human plasma.
Results: Reconstituted plasma samples that correspond to non-carrier, heterozygous carrier, and homozygous mutation carrier plasma were reconstructed. Recombinant proteinstested by OHP assay were
functional.
Conclusion: Reconstituted plasma samples allow us to examine the mechanism of prothrombin Belgrade mutation in various assays and in homozygous form as well.",
publisher = "Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade",
journal = "CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia",
title = "Reconstitution of non-carrier, heterozygous and homozygous prothrombin belgrade mutation carrier plasma using recombinant proteins",
pages = "71-71",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2123"
}

Dunjić Manevski, S., Cumbo, M., Gvozdenov, M., Tomić, B., Ušjak, D.,& Đorđević, V.. (2023). Reconstitution of non-carrier, heterozygous and homozygous prothrombin belgrade mutation carrier plasma using recombinant proteins. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia
Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade., 71-71.
https://hdl.handle.net/21.15107/rcub_imagine_2123

Dunjić Manevski S, Cumbo M, Gvozdenov M, Tomić B, Ušjak D, Đorđević V. Reconstitution of non-carrier, heterozygous and homozygous prothrombin belgrade mutation carrier plasma using recombinant proteins. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia. 2023;:71-71.
https://hdl.handle.net/21.15107/rcub_imagine_2123 .

Dunjić Manevski, Sofija, Cumbo, Marija, Gvozdenov, Maja, Tomić, Branko, Ušjak, Dušan, Đorđević, Valentina, "Reconstitution of non-carrier, heterozygous and homozygous prothrombin belgrade mutation carrier plasma using recombinant proteins" in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia (2023):71-71,
https://hdl.handle.net/21.15107/rcub_imagine_2123 .

TY  - JOUR
AU  - Ušjak, Dušan
AU  - Novović, Katarina
AU  - Ivković, Branka
AU  - Tomić, Branko
AU  - Đorđević, Valentina
AU  - Milenković, Marina
PY  - 2023
UR  - https://doi.org/10.1080/08927014.2023.2215693
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1896
AB  - Biofilm production facilitates microbial colonization of wounds and catheters. Acinetobacter baumannii produces high levels of biofilm and causes difficult-to-treat nosocomial infections. Candida albicans is another strong biofilm producer which may facilitate A. baumannii adhesion by providing hyphae-mediated OmpA-binding sites. Here we tested the potential of 2′-hydroxychalcones to inhibit dual-species biofilm production of A. baumannii and Candida spp., and further predicted the mechanism of structure-related difference in activity. The results suggest that 2′-hydroxychalcones exhibit potent activity against Candida spp./A. baumannii dual-species biofilm production. Particularly active was trifluoromethyl-substituted derivative (p-CF3), which decreased C. albicans/A. baumannii biomass produced on vein-indwelling parts of the central venous catheterization set by up to 99%. Further, higher OmpA-binding affinity was also calculated for p-CF3, which together with demonstrated significant ompA-downregulating activity, suggests that superior antibiofilm activity of this chalcone against the tested dual-species community of A. baumannii is mediated through the OmpA.
T2  - Biofouling
T2  - Biofouling
T1  - Targeting outer membrane protein A (OmpA) – inhibitory effect of 2′-hydroxychalcone derivatives on Acinetobacter baumannii and Candida albicans dual-species biofilm formation
EP  - 11
SP  - 1
DO  - 10.1080/08927014.2023.2215693
ER  - 

@article{
author = "Ušjak, Dušan and Novović, Katarina and Ivković, Branka and Tomić, Branko and Đorđević, Valentina and Milenković, Marina",
year = "2023",
abstract = "Biofilm production facilitates microbial colonization of wounds and catheters. Acinetobacter baumannii produces high levels of biofilm and causes difficult-to-treat nosocomial infections. Candida albicans is another strong biofilm producer which may facilitate A. baumannii adhesion by providing hyphae-mediated OmpA-binding sites. Here we tested the potential of 2′-hydroxychalcones to inhibit dual-species biofilm production of A. baumannii and Candida spp., and further predicted the mechanism of structure-related difference in activity. The results suggest that 2′-hydroxychalcones exhibit potent activity against Candida spp./A. baumannii dual-species biofilm production. Particularly active was trifluoromethyl-substituted derivative (p-CF3), which decreased C. albicans/A. baumannii biomass produced on vein-indwelling parts of the central venous catheterization set by up to 99%. Further, higher OmpA-binding affinity was also calculated for p-CF3, which together with demonstrated significant ompA-downregulating activity, suggests that superior antibiofilm activity of this chalcone against the tested dual-species community of A. baumannii is mediated through the OmpA.",
journal = "Biofouling, Biofouling",
title = "Targeting outer membrane protein A (OmpA) – inhibitory effect of 2′-hydroxychalcone derivatives on Acinetobacter baumannii and Candida albicans dual-species biofilm formation",
pages = "11-1",
doi = "10.1080/08927014.2023.2215693"
}

Ušjak, D., Novović, K., Ivković, B., Tomić, B., Đorđević, V.,& Milenković, M.. (2023). Targeting outer membrane protein A (OmpA) – inhibitory effect of 2′-hydroxychalcone derivatives on Acinetobacter baumannii and Candida albicans dual-species biofilm formation. in Biofouling, 1-11.
https://doi.org/10.1080/08927014.2023.2215693

Ušjak D, Novović K, Ivković B, Tomić B, Đorđević V, Milenković M. Targeting outer membrane protein A (OmpA) – inhibitory effect of 2′-hydroxychalcone derivatives on Acinetobacter baumannii and Candida albicans dual-species biofilm formation. in Biofouling. 2023;:1-11.
doi:10.1080/08927014.2023.2215693 .

Ušjak, Dušan, Novović, Katarina, Ivković, Branka, Tomić, Branko, Đorđević, Valentina, Milenković, Marina, "Targeting outer membrane protein A (OmpA) – inhibitory effect of 2′-hydroxychalcone derivatives on Acinetobacter baumannii and Candida albicans dual-species biofilm formation" in Biofouling (2023):1-11,
https://doi.org/10.1080/08927014.2023.2215693 . .

TY  - CONF
AU  - Mitić, Martina Mia
AU  - Ušjak, Dušan
AU  - Milošević, Maja
AU  - Cumbo, Marija
AU  - Dunjić Manevski, Sofija
AU  - Tomić, Branko
AU  - Petrović, Ivana
AU  - Otašević, Petar
AU  - Micović, Slobodan
AU  - Bojić, Milovan
AU  - Đorđević, Valentina
PY  - 2023
UR  - https://belbi.bg.ac.rs/
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1999
AB  - Normal aortic valve consists of three cusps that develop in the embryonic stage. Unicuspid
aortic valve (UAV) is a rare congenital anomaly resulting in only one cusp with estimated
prevalence of 0.02% in general population. Aim of this study was to identify genetic
variants possibly associated with development of UAV. The study included 17 subjects,
namely 5 UAV patients and their healthy family members without UAV disorder. Total
DNA was isolated from venous blood samples and whole exomes sequencing (WES) was
performed using BGI’s WES protocol. Adapter-trimmed and quality-filtered reads (fastp)
were mapped to hg38 reference genome using BWA/SAMtools. VCF files were generated
using GATK (BaseRecalibrator, HaplotypeCaller) and annotated with InterVar and AnnoVar
tools. Rare heterozygous variants present in UAV patients were found in NOTCH1, TGFB2,
MYH6, EGFR, FBN2, C1R, ROBO4 and TBX5, genes associated with development of aortic
valves. Among these, most were missense mutations with damaging effects as predicted
using in silico tools (SIFT and/or Polyphen). Only mutation in MYH6 p.Ala1130Ser was
found in at least two different UAV patients. Also, rare homozygous missense mutation
p.Gly577Ser with high damaging potential was found in ADAMTS5 gene. Besides, highly
damaging heterozygous missense mutations were detected in gene interacting functional
partners (STRING) of genes associated with development of aortic valves: DVL1, THBS1,
NOTCH4, ADAMTS3, FBN1, NOTCH2, ADAM17, LRP5, WWTR1, C1S, ANKRD6 and TNNI1,
as well as homozygous in ACAN and KNG1. Taken together, malfunctions in ADAMTS5,
ACTA2, MYH6, FBN2, AXIN1, CELSR1 or TBX5 networks were found to be common in at
least two UAV patients, suggesting existence of genetic basis in UAV disorder, possibly as
a result of combined effects of multiple variants.
PB  - Belgrade : Institute of molecular genetics and genetic engineering
C3  - 4th Belgrade Bioinformatics Conference
T1  - Using whole exome sequencing to explore genetic basis of unicuspid aortic valve disease
EP  - 59
SP  - 59
VL  - 4
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1999
ER  - 

@conference{
author = "Mitić, Martina Mia and Ušjak, Dušan and Milošević, Maja and Cumbo, Marija and Dunjić Manevski, Sofija and Tomić, Branko and Petrović, Ivana and Otašević, Petar and Micović, Slobodan and Bojić, Milovan and Đorđević, Valentina",
year = "2023",
abstract = "Normal aortic valve consists of three cusps that develop in the embryonic stage. Unicuspid
aortic valve (UAV) is a rare congenital anomaly resulting in only one cusp with estimated
prevalence of 0.02% in general population. Aim of this study was to identify genetic
variants possibly associated with development of UAV. The study included 17 subjects,
namely 5 UAV patients and their healthy family members without UAV disorder. Total
DNA was isolated from venous blood samples and whole exomes sequencing (WES) was
performed using BGI’s WES protocol. Adapter-trimmed and quality-filtered reads (fastp)
were mapped to hg38 reference genome using BWA/SAMtools. VCF files were generated
using GATK (BaseRecalibrator, HaplotypeCaller) and annotated with InterVar and AnnoVar
tools. Rare heterozygous variants present in UAV patients were found in NOTCH1, TGFB2,
MYH6, EGFR, FBN2, C1R, ROBO4 and TBX5, genes associated with development of aortic
valves. Among these, most were missense mutations with damaging effects as predicted
using in silico tools (SIFT and/or Polyphen). Only mutation in MYH6 p.Ala1130Ser was
found in at least two different UAV patients. Also, rare homozygous missense mutation
p.Gly577Ser with high damaging potential was found in ADAMTS5 gene. Besides, highly
damaging heterozygous missense mutations were detected in gene interacting functional
partners (STRING) of genes associated with development of aortic valves: DVL1, THBS1,
NOTCH4, ADAMTS3, FBN1, NOTCH2, ADAM17, LRP5, WWTR1, C1S, ANKRD6 and TNNI1,
as well as homozygous in ACAN and KNG1. Taken together, malfunctions in ADAMTS5,
ACTA2, MYH6, FBN2, AXIN1, CELSR1 or TBX5 networks were found to be common in at
least two UAV patients, suggesting existence of genetic basis in UAV disorder, possibly as
a result of combined effects of multiple variants.",
publisher = "Belgrade : Institute of molecular genetics and genetic engineering",
journal = "4th Belgrade Bioinformatics Conference",
title = "Using whole exome sequencing to explore genetic basis of unicuspid aortic valve disease",
pages = "59-59",
volume = "4",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1999"
}

Mitić, M. M., Ušjak, D., Milošević, M., Cumbo, M., Dunjić Manevski, S., Tomić, B., Petrović, I., Otašević, P., Micović, S., Bojić, M.,& Đorđević, V.. (2023). Using whole exome sequencing to explore genetic basis of unicuspid aortic valve disease. in 4th Belgrade Bioinformatics Conference
Belgrade : Institute of molecular genetics and genetic engineering., 4, 59-59.
https://hdl.handle.net/21.15107/rcub_imagine_1999

Mitić MM, Ušjak D, Milošević M, Cumbo M, Dunjić Manevski S, Tomić B, Petrović I, Otašević P, Micović S, Bojić M, Đorđević V. Using whole exome sequencing to explore genetic basis of unicuspid aortic valve disease. in 4th Belgrade Bioinformatics Conference. 2023;4:59-59.
https://hdl.handle.net/21.15107/rcub_imagine_1999 .

Mitić, Martina Mia, Ušjak, Dušan, Milošević, Maja, Cumbo, Marija, Dunjić Manevski, Sofija, Tomić, Branko, Petrović, Ivana, Otašević, Petar, Micović, Slobodan, Bojić, Milovan, Đorđević, Valentina, "Using whole exome sequencing to explore genetic basis of unicuspid aortic valve disease" in 4th Belgrade Bioinformatics Conference, 4 (2023):59-59,
https://hdl.handle.net/21.15107/rcub_imagine_1999 .

TY  - JOUR
AU  - Malod-Dognin, Noël
AU  - Ceddia, Gaia
AU  - Gvozdenov, Maja
AU  - Tomić, Branko
AU  - Manevski Dunjić, Sofija 
AU  - Đorđević, Valentina
AU  - Pržulj, Nataša
PY  - 2023
UR  - https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0284084
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1920
AB  - Antithrombin resistance is a rare subtype of hereditary thrombophilia caused by prothrombin gene variants, leading to thrombotic disorders. Recently, the Prothrombin Belgrade variant has been reported as a specific variant that leads to antithrombin resistance in two Serbian families with thrombosis. However, due to clinical data scarcity and the inapplicability of traditional genome-wide association studies (GWAS), a broader perspective on molecular and phenotypic mechanisms associated with the Prothrombin Belgrade variant is yet to be uncovered. Here, we propose an integrative framework to address the lack of genomic samples and support the genomic signal from the full genome sequences of five heterozygous subjects by integrating it with subjects’ phenotypes and the genes’ molecular interactions. Our goal is to identify candidate thrombophilia-related genes for which our subjects possess germline variants by focusing on the resulting gene clusters of our integrative framework. We applied a Non-negative Matrix Tri-Factorization-based method to simultaneously integrate different data sources, taking into account the observed phenotypes. In other words, our data-integration framework reveals gene clusters involved with this rare disease by fusing different datasets. Our results are in concordance with the current literature about antithrombin resistance. We also found candidate disease-related genes that need to be further investigated. CD320, RTEL1, UCP2, APOA5 and PROZ participate in healthy-specific or disease-specific subnetworks involving thrombophilia-annotated genes and are related to general thrombophilia mechanisms according to the literature. Moreover, the ADRA2A and TBXA2R subnetworks analysis suggested that their variants may have a protective effect due to their connection with decreased platelet activation. The results show that our method can give insights into antithrombin resistance even if a small amount of genetic data is available. Our framework is also customizable, meaning that it applies to any other rare disease.
T2  - Plos one
T1  - A phenotype driven integrative framework uncovers molecular mechanisms of a rare hereditary thrombophilia
IS  - 4
SP  - e0284084
VL  - 18
DO  - 10.1371/journal.pone.0284084
ER  - 

@article{
author = "Malod-Dognin, Noël and Ceddia, Gaia and Gvozdenov, Maja and Tomić, Branko and Manevski Dunjić, Sofija  and Đorđević, Valentina and Pržulj, Nataša",
year = "2023",
abstract = "Antithrombin resistance is a rare subtype of hereditary thrombophilia caused by prothrombin gene variants, leading to thrombotic disorders. Recently, the Prothrombin Belgrade variant has been reported as a specific variant that leads to antithrombin resistance in two Serbian families with thrombosis. However, due to clinical data scarcity and the inapplicability of traditional genome-wide association studies (GWAS), a broader perspective on molecular and phenotypic mechanisms associated with the Prothrombin Belgrade variant is yet to be uncovered. Here, we propose an integrative framework to address the lack of genomic samples and support the genomic signal from the full genome sequences of five heterozygous subjects by integrating it with subjects’ phenotypes and the genes’ molecular interactions. Our goal is to identify candidate thrombophilia-related genes for which our subjects possess germline variants by focusing on the resulting gene clusters of our integrative framework. We applied a Non-negative Matrix Tri-Factorization-based method to simultaneously integrate different data sources, taking into account the observed phenotypes. In other words, our data-integration framework reveals gene clusters involved with this rare disease by fusing different datasets. Our results are in concordance with the current literature about antithrombin resistance. We also found candidate disease-related genes that need to be further investigated. CD320, RTEL1, UCP2, APOA5 and PROZ participate in healthy-specific or disease-specific subnetworks involving thrombophilia-annotated genes and are related to general thrombophilia mechanisms according to the literature. Moreover, the ADRA2A and TBXA2R subnetworks analysis suggested that their variants may have a protective effect due to their connection with decreased platelet activation. The results show that our method can give insights into antithrombin resistance even if a small amount of genetic data is available. Our framework is also customizable, meaning that it applies to any other rare disease.",
journal = "Plos one",
title = "A phenotype driven integrative framework uncovers molecular mechanisms of a rare hereditary thrombophilia",
number = "4",
pages = "e0284084",
volume = "18",
doi = "10.1371/journal.pone.0284084"
}

Malod-Dognin, N., Ceddia, G., Gvozdenov, M., Tomić, B., Manevski Dunjić, S., Đorđević, V.,& Pržulj, N.. (2023). A phenotype driven integrative framework uncovers molecular mechanisms of a rare hereditary thrombophilia. in Plos one, 18(4), e0284084.
https://doi.org/10.1371/journal.pone.0284084

Malod-Dognin N, Ceddia G, Gvozdenov M, Tomić B, Manevski Dunjić S, Đorđević V, Pržulj N. A phenotype driven integrative framework uncovers molecular mechanisms of a rare hereditary thrombophilia. in Plos one. 2023;18(4):e0284084.
doi:10.1371/journal.pone.0284084 .

Malod-Dognin, Noël, Ceddia, Gaia, Gvozdenov, Maja, Tomić, Branko, Manevski Dunjić, Sofija , Đorđević, Valentina, Pržulj, Nataša, "A phenotype driven integrative framework uncovers molecular mechanisms of a rare hereditary thrombophilia" in Plos one, 18, no. 4 (2023):e0284084,
https://doi.org/10.1371/journal.pone.0284084 . .

TY  - CONF
AU  - Cumbo, Marija
AU  - Tomić, Branko
AU  - Dunjić Manevski, Sofija
AU  - Gvozdenov, Maja
AU  - Ušjak, Dušan
AU  - Mitić, Martina Mia
AU  - Đorđević, Valentina
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2135
AB  - Introduction: Thrombin, crucial member of the coagulation cascade, can influence growth and development of different types of cancer. Prothrombin, thrombin precursor, although predominantly secreted
from the liver into the bloodstream, can also be expressed in the cancer cells. According to latest data prothrombin can bind in vitro to transmembrane receptors, which have previously been shown to be up-regulated in cancers and activate migration and invasion. Despite the significant amount of data on the
effects of thrombin in cancer progression, there are little data of prothrombin´s effect. The aim of this
study was to further examine the effects of prothrombin and thrombin in cancer cell lines.
Methods: Colon cancer cell lines (Caco2, SW480, SW620, HT29 and HCT116) were treated with prothrombin, thrombin and direct thrombin inhibitor, dabigatran, for 24h and 48h. To assess the effects of
treatment on cell viability and proliferation MTT test was used, and wound healing assay was used for cell
migration potential.
Results: Detected effects of treatment with prothrombin, thrombin and dabigatran varied between cell
lines. Trend of lower cell viability, proliferation and migration was observed in cells treated with prothrombin in comparison to untreated controls.
Conclusion: Our resultsindicate that prothrombin, although considered an inactive zymogen, can exert
an effect on colon cancer cells proliferation and migration in vitro.
PB  - Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade
C3  - CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia
T1  - Prothrombin influences proliferation and migration of colon cancer in vitro
EP  - 156
SP  - 156
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2135
ER  - 

@conference{
author = "Cumbo, Marija and Tomić, Branko and Dunjić Manevski, Sofija and Gvozdenov, Maja and Ušjak, Dušan and Mitić, Martina Mia and Đorđević, Valentina",
year = "2023",
abstract = "Introduction: Thrombin, crucial member of the coagulation cascade, can influence growth and development of different types of cancer. Prothrombin, thrombin precursor, although predominantly secreted
from the liver into the bloodstream, can also be expressed in the cancer cells. According to latest data prothrombin can bind in vitro to transmembrane receptors, which have previously been shown to be up-regulated in cancers and activate migration and invasion. Despite the significant amount of data on the
effects of thrombin in cancer progression, there are little data of prothrombin´s effect. The aim of this
study was to further examine the effects of prothrombin and thrombin in cancer cell lines.
Methods: Colon cancer cell lines (Caco2, SW480, SW620, HT29 and HCT116) were treated with prothrombin, thrombin and direct thrombin inhibitor, dabigatran, for 24h and 48h. To assess the effects of
treatment on cell viability and proliferation MTT test was used, and wound healing assay was used for cell
migration potential.
Results: Detected effects of treatment with prothrombin, thrombin and dabigatran varied between cell
lines. Trend of lower cell viability, proliferation and migration was observed in cells treated with prothrombin in comparison to untreated controls.
Conclusion: Our resultsindicate that prothrombin, although considered an inactive zymogen, can exert
an effect on colon cancer cells proliferation and migration in vitro.",
publisher = "Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade",
journal = "CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia",
title = "Prothrombin influences proliferation and migration of colon cancer in vitro",
pages = "156-156",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2135"
}

Cumbo, M., Tomić, B., Dunjić Manevski, S., Gvozdenov, M., Ušjak, D., Mitić, M. M.,& Đorđević, V.. (2023). Prothrombin influences proliferation and migration of colon cancer in vitro. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia
Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade., 156-156.
https://hdl.handle.net/21.15107/rcub_imagine_2135

Cumbo M, Tomić B, Dunjić Manevski S, Gvozdenov M, Ušjak D, Mitić MM, Đorđević V. Prothrombin influences proliferation and migration of colon cancer in vitro. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia. 2023;:156-156.
https://hdl.handle.net/21.15107/rcub_imagine_2135 .

Cumbo, Marija, Tomić, Branko, Dunjić Manevski, Sofija, Gvozdenov, Maja, Ušjak, Dušan, Mitić, Martina Mia, Đorđević, Valentina, "Prothrombin influences proliferation and migration of colon cancer in vitro" in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia (2023):156-156,
https://hdl.handle.net/21.15107/rcub_imagine_2135 .

TY  - JOUR
AU  - Kovač, Mirjana
AU  - Basarić, Dušica
AU  - Tomić, Branko
AU  - Gvozdenov, Maja
AU  - Backović, Dragana
AU  - Lalić-Ćosić, Sanja
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1914
AB  - Direct oral anticoagulants (DOACs) administration significantly interferes with coagulation as-says. The aim of the study was to evaluate the effect of DOACs and DOAC-Remove® on coagulation assays dur-ing thrombophilia testing. Methods. The study was car-ried out from January 2019 to the end of June 2020. It in-cluded 30 DOAC-treated patients, 14 females and 16 males aged 23 to 63 (median age 47.6 years), tested for thrombophilia due to venous thromboembolism (VTE). Thrombophilia testing was performed using DOAC-Remove® tablets (activated charcoal). The results before and after DOAC-Remove® were compared. Results. Posi-tive lupus anticoagulant (LA) results were observed in 20% apixaban, 100% dabigatran, and 70% rivaroxaban-treated patients, while in samples after DOAC-Remove®, the LA positivity was observed only in one from the apix-aban group. Before DOAC-Remove®, the activated pro-tein C (APC) resistance (APC-R) was measurable in 40% dabigatran and 80% rivaroxaban-treated patients, while, after using DOAC-Remove®, the APC-R was measurable in all cases. Comparing the results obtained from the sam-ples before and after DOAC-Remove®, a difference was noted in relation to all dilute Russell's viper venom time (dRVVT) coagulation tests, except for the dRVVT ratio in the apixaban group. Clot-based methods for detecting the APC resistance were significantly affected by dabigatran and less by rivaroxaban. Conclusion. DOACs were prac-tically inactivated after the addition of the DOAC-Remove®, which made it possible to perform analyses for the LA and APC-R testing freely and obtain relevant re-sults.
AB  - Primena direktnih oralnih antikoagulansa (DOAK)značajno utiče na testove koagulacije. Cilj rada bio je da se pro-ceni uticaj DOAK i DOAC-Remove® tableta (aktivni ugalj) natestove koagulacije tokom ispitivanja trombofilije. Metode.Istraživanjem, sprovedenim od januara 2019. do juna 2020.godine, obuhvaćeno je 30 bolesnika lečenih DOAK-om itestiranih na trombofiliju zbog venskog tromboembolzma(VTE). Bilo je 14 žena i 16 muškaraca, starosti od 23 do 63godine (medijana 47,6 godina). Ispitivanje trombofilije izvršenoje upotrebom DOAC-Remove® tableta (aktivni ugalj).Upoređivani su rezultati pre i posle primene DOAC-Remove®.Rezultati. Pozitivni rezultati za lupus antikoagulantni (LA) testdobijeni su kod 20% bolesnika lečenih apiksabanom, kod100% bolesnika lečenih dabigatranom i kod 70% lečenih riva-roksabanom, a u uzorcima posle DOAC-Remove® pozitivnostna LA dobijena je samo kod jednog bolesnika iz grupe lečnihapiksabanom. Pre primene DOAC-Remove®, rezistencija naaktivisani protein C (activated protein C resistance – APC-R) bila jemerljiva kod 40% i 80% bolesnika lečenih dabigatranom, od-nosno rivaroksabanom, dok je posle primene DOAC-Remove®, APC-R bila merljiva u svim slučajevima.Upoređivanjem rezultata dobijenih iz uzoraka pre i posleprimene DOAC-Remove®, primećena je razlika u odnosu nasve testove vremena koagulacije izvršene razblaženim Russell-ovim zmijskim otrovom (dilute Russell’s viper venom time –dRVVT), osim dRVVT u grupi bolesnika lečenih apiksabanom.Na koagulacionu metodu za otkrivanje APC-R značajno je uti-cao dabigatran, a manje rivaroksaban. Zaključak. Nakonprimene DOAC-Remove® tableta, DOAK su praktičnoinaktivisani što je omogućilo izvođenje analiza za LA i APC-R idobijanje relevantnih rezultata testova.
PB  - Inst. Sci. inf., Univ. Defence in Belgrade
T2  - Vojnosanitetski Pregled
T1  - Influence of DOACS and DOAC-REMOVE® on coagulation assays during thrombophilia testing in DOAC-treated patients
T1  - Uticaj DOAK i DOAC-REMOVE® na testove koagulacije u toku testiranjatrombofilije kod bolesnika lečenih primenom DOAK
EP  - 1254
IS  - 12
SP  - 1248
VL  - 79
DO  - 10.2298/VSP210217101K
ER  - 

@article{
author = "Kovač, Mirjana and Basarić, Dušica and Tomić, Branko and Gvozdenov, Maja and Backović, Dragana and Lalić-Ćosić, Sanja",
year = "2022",
abstract = "Direct oral anticoagulants (DOACs) administration significantly interferes with coagulation as-says. The aim of the study was to evaluate the effect of DOACs and DOAC-Remove® on coagulation assays dur-ing thrombophilia testing. Methods. The study was car-ried out from January 2019 to the end of June 2020. It in-cluded 30 DOAC-treated patients, 14 females and 16 males aged 23 to 63 (median age 47.6 years), tested for thrombophilia due to venous thromboembolism (VTE). Thrombophilia testing was performed using DOAC-Remove® tablets (activated charcoal). The results before and after DOAC-Remove® were compared. Results. Posi-tive lupus anticoagulant (LA) results were observed in 20% apixaban, 100% dabigatran, and 70% rivaroxaban-treated patients, while in samples after DOAC-Remove®, the LA positivity was observed only in one from the apix-aban group. Before DOAC-Remove®, the activated pro-tein C (APC) resistance (APC-R) was measurable in 40% dabigatran and 80% rivaroxaban-treated patients, while, after using DOAC-Remove®, the APC-R was measurable in all cases. Comparing the results obtained from the sam-ples before and after DOAC-Remove®, a difference was noted in relation to all dilute Russell's viper venom time (dRVVT) coagulation tests, except for the dRVVT ratio in the apixaban group. Clot-based methods for detecting the APC resistance were significantly affected by dabigatran and less by rivaroxaban. Conclusion. DOACs were prac-tically inactivated after the addition of the DOAC-Remove®, which made it possible to perform analyses for the LA and APC-R testing freely and obtain relevant re-sults., Primena direktnih oralnih antikoagulansa (DOAK)značajno utiče na testove koagulacije. Cilj rada bio je da se pro-ceni uticaj DOAK i DOAC-Remove® tableta (aktivni ugalj) natestove koagulacije tokom ispitivanja trombofilije. Metode.Istraživanjem, sprovedenim od januara 2019. do juna 2020.godine, obuhvaćeno je 30 bolesnika lečenih DOAK-om itestiranih na trombofiliju zbog venskog tromboembolzma(VTE). Bilo je 14 žena i 16 muškaraca, starosti od 23 do 63godine (medijana 47,6 godina). Ispitivanje trombofilije izvršenoje upotrebom DOAC-Remove® tableta (aktivni ugalj).Upoređivani su rezultati pre i posle primene DOAC-Remove®.Rezultati. Pozitivni rezultati za lupus antikoagulantni (LA) testdobijeni su kod 20% bolesnika lečenih apiksabanom, kod100% bolesnika lečenih dabigatranom i kod 70% lečenih riva-roksabanom, a u uzorcima posle DOAC-Remove® pozitivnostna LA dobijena je samo kod jednog bolesnika iz grupe lečnihapiksabanom. Pre primene DOAC-Remove®, rezistencija naaktivisani protein C (activated protein C resistance – APC-R) bila jemerljiva kod 40% i 80% bolesnika lečenih dabigatranom, od-nosno rivaroksabanom, dok je posle primene DOAC-Remove®, APC-R bila merljiva u svim slučajevima.Upoređivanjem rezultata dobijenih iz uzoraka pre i posleprimene DOAC-Remove®, primećena je razlika u odnosu nasve testove vremena koagulacije izvršene razblaženim Russell-ovim zmijskim otrovom (dilute Russell’s viper venom time –dRVVT), osim dRVVT u grupi bolesnika lečenih apiksabanom.Na koagulacionu metodu za otkrivanje APC-R značajno je uti-cao dabigatran, a manje rivaroksaban. Zaključak. Nakonprimene DOAC-Remove® tableta, DOAK su praktičnoinaktivisani što je omogućilo izvođenje analiza za LA i APC-R idobijanje relevantnih rezultata testova.",
publisher = "Inst. Sci. inf., Univ. Defence in Belgrade",
journal = "Vojnosanitetski Pregled",
title = "Influence of DOACS and DOAC-REMOVE® on coagulation assays during thrombophilia testing in DOAC-treated patients, Uticaj DOAK i DOAC-REMOVE® na testove koagulacije u toku testiranjatrombofilije kod bolesnika lečenih primenom DOAK",
pages = "1254-1248",
number = "12",
volume = "79",
doi = "10.2298/VSP210217101K"
}

Kovač, M., Basarić, D., Tomić, B., Gvozdenov, M., Backović, D.,& Lalić-Ćosić, S.. (2022). Influence of DOACS and DOAC-REMOVE® on coagulation assays during thrombophilia testing in DOAC-treated patients. in Vojnosanitetski Pregled
Inst. Sci. inf., Univ. Defence in Belgrade., 79(12), 1248-1254.
https://doi.org/10.2298/VSP210217101K

Kovač M, Basarić D, Tomić B, Gvozdenov M, Backović D, Lalić-Ćosić S. Influence of DOACS and DOAC-REMOVE® on coagulation assays during thrombophilia testing in DOAC-treated patients. in Vojnosanitetski Pregled. 2022;79(12):1248-1254.
doi:10.2298/VSP210217101K .

Kovač, Mirjana, Basarić, Dušica, Tomić, Branko, Gvozdenov, Maja, Backović, Dragana, Lalić-Ćosić, Sanja, "Influence of DOACS and DOAC-REMOVE® on coagulation assays during thrombophilia testing in DOAC-treated patients" in Vojnosanitetski Pregled, 79, no. 12 (2022):1248-1254,
https://doi.org/10.2298/VSP210217101K . .

TY  - CONF
AU  - Tomić, Branko
AU  - Gvozdenov, Maja
AU  - Cumbo, Marija
AU  - Dunjić Manevski, Sofija
AU  - Đorđević, Valentina
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1739
AB  - Trombofilija je patofiziološko stanje povećanog rizika za nastanak
hiperkoagulacije, koja može dovesti do začepljenja krvnog suda (tromboze).
Faktori rizika za nastanak ove multifaktorijalne bolesti mogu biti sredinski,
uzrokovani načinom života, i nasledni (genetski). Do sada je identifikovan
veliki broj naslednih faktora rizika, uglavnom tačkastih mutacija u genima za
proteine hemostaznog sistema. Iako se ove mutacije analiziraju u okviru
rutinskih kliničkih testova, kod značajnog broja bolesnika i nakon sprovedenih
dijagnostičkih procedura, uzrok trombotičkog događaja ostaje nepoznat, što
implicira postojanje neidentifikovanih naslednih faktora rizika. U cilju
njihove identifikacije, vrše se dalje genske analize, asocijativne studije,
karakterizacije potencijalnih faktora rizika u in vitro i in vivo studijama na
različitim model sistemima. U našem dosadašnjem radu detektovano je više
varijanti u kodirajućem i nekodirajućem regionu gena, za koje je karakterizacijom
utvrđeno da utiču na ekspresiju i/ili funcionalnost koagulacionih proteina.
Primenom sekvenciranja nove generacije i bioinformatičke obrade, omogućena je
sveobuhvatnija analiza celokupnog genoma i identifikacija klastera gena koji su
povezani sa kompleksnom kliničkom slikom tromboza. Kombinovanjem velikog
broja podataka o genetskim i sredinskim faktorima, primenom veštačke
inteligencije, otvara se mogućnost kompletnijeg sagledavanja mehanizama
trombofilije i multifaktorijalnih bolesti uopšte.
AB  - Тромбофилија је патофизиолошко стање повећаног ризика за настанак
хиперкоагулације, која може довести до зачепљења крвног суда (тромбозе).
Фактори ризика за настанак ове мултифакторијалне болести могу бити средински,
узроковани начином живота, и наследни (генетски). До сада је идентификован
велики број наследних фактора ризика, углавном тачкастих мутација у генима за
протеине хемостазног система. Иако се ове мутације анализирају у оквиру
рутинских клиничких тестова, код значајног броја болесника и након спроведених
дијагностичких процедура, узрок тромботичког догађаја остаје непознат, што
имплицира постојање неидентификованих наследних фактора ризика. У циљу
њихове идентификације, врше се даље генске анализе, асоцијативне студије,
карактеризације потенцијалних фактора ризика у in vitro и in vivo студијама на
различитим модел системима. У нашем досадашњем раду детектовано је више
варијанти у кодирајућем и некодирајућем региону гена, за које је карактеризацијом
утврђено да утичу на експресију и/или фунционалност коагулационих протеина.
Применом секвенцирања нове генерације и биоинформатичке обраде, омогућена је
свеобухватнија анализа целокупног генома и идентификација кластера гена који су
повезани са комплексном клиничком сликом тромбоза. Комбиновањем великог
броја података о генетским и срединским факторима, применом вештачке
интелигенције, отвара се могућност комплетнијег сагледавања механизама
тромбофилије и мултифакторијалних болести уопште.
PB  - Beograd : Srpsko biološko društvo
C3  - Treći kongres biologa Srbije
T1  - Nasledni faktori rizika za trombofiliju – od tačkastih mutacija do primene veštačke inteligencije
T1  - Наследни фактори ризика за тромбофилију – од тачкастих мутација до примене вештачке интелигенције
SP  - 278
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1739
ER  - 

@conference{
author = "Tomić, Branko and Gvozdenov, Maja and Cumbo, Marija and Dunjić Manevski, Sofija and Đorđević, Valentina",
year = "2022",
abstract = "Trombofilija je patofiziološko stanje povećanog rizika za nastanak
hiperkoagulacije, koja može dovesti do začepljenja krvnog suda (tromboze).
Faktori rizika za nastanak ove multifaktorijalne bolesti mogu biti sredinski,
uzrokovani načinom života, i nasledni (genetski). Do sada je identifikovan
veliki broj naslednih faktora rizika, uglavnom tačkastih mutacija u genima za
proteine hemostaznog sistema. Iako se ove mutacije analiziraju u okviru
rutinskih kliničkih testova, kod značajnog broja bolesnika i nakon sprovedenih
dijagnostičkih procedura, uzrok trombotičkog događaja ostaje nepoznat, što
implicira postojanje neidentifikovanih naslednih faktora rizika. U cilju
njihove identifikacije, vrše se dalje genske analize, asocijativne studije,
karakterizacije potencijalnih faktora rizika u in vitro i in vivo studijama na
različitim model sistemima. U našem dosadašnjem radu detektovano je više
varijanti u kodirajućem i nekodirajućem regionu gena, za koje je karakterizacijom
utvrđeno da utiču na ekspresiju i/ili funcionalnost koagulacionih proteina.
Primenom sekvenciranja nove generacije i bioinformatičke obrade, omogućena je
sveobuhvatnija analiza celokupnog genoma i identifikacija klastera gena koji su
povezani sa kompleksnom kliničkom slikom tromboza. Kombinovanjem velikog
broja podataka o genetskim i sredinskim faktorima, primenom veštačke
inteligencije, otvara se mogućnost kompletnijeg sagledavanja mehanizama
trombofilije i multifaktorijalnih bolesti uopšte., Тромбофилија је патофизиолошко стање повећаног ризика за настанак
хиперкоагулације, која може довести до зачепљења крвног суда (тромбозе).
Фактори ризика за настанак ове мултифакторијалне болести могу бити средински,
узроковани начином живота, и наследни (генетски). До сада је идентификован
велики број наследних фактора ризика, углавном тачкастих мутација у генима за
протеине хемостазног система. Иако се ове мутације анализирају у оквиру
рутинских клиничких тестова, код значајног броја болесника и након спроведених
дијагностичких процедура, узрок тромботичког догађаја остаје непознат, што
имплицира постојање неидентификованих наследних фактора ризика. У циљу
њихове идентификације, врше се даље генске анализе, асоцијативне студије,
карактеризације потенцијалних фактора ризика у in vitro и in vivo студијама на
различитим модел системима. У нашем досадашњем раду детектовано је више
варијанти у кодирајућем и некодирајућем региону гена, за које је карактеризацијом
утврђено да утичу на експресију и/или фунционалност коагулационих протеина.
Применом секвенцирања нове генерације и биоинформатичке обраде, омогућена је
свеобухватнија анализа целокупног генома и идентификација кластера гена који су
повезани са комплексном клиничком сликом тромбоза. Комбиновањем великог
броја података о генетским и срединским факторима, применом вештачке
интелигенције, отвара се могућност комплетнијег сагледавања механизама
тромбофилије и мултифакторијалних болести уопште.",
publisher = "Beograd : Srpsko biološko društvo",
journal = "Treći kongres biologa Srbije",
title = "Nasledni faktori rizika za trombofiliju – od tačkastih mutacija do primene veštačke inteligencije, Наследни фактори ризика за тромбофилију – од тачкастих мутација до примене вештачке интелигенције",
pages = "278",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1739"
}

Tomić, B., Gvozdenov, M., Cumbo, M., Dunjić Manevski, S.,& Đorđević, V.. (2022). Nasledni faktori rizika za trombofiliju – od tačkastih mutacija do primene veštačke inteligencije. in Treći kongres biologa Srbije
Beograd : Srpsko biološko društvo., 278.
https://hdl.handle.net/21.15107/rcub_imagine_1739

Tomić B, Gvozdenov M, Cumbo M, Dunjić Manevski S, Đorđević V. Nasledni faktori rizika za trombofiliju – od tačkastih mutacija do primene veštačke inteligencije. in Treći kongres biologa Srbije. 2022;:278.
https://hdl.handle.net/21.15107/rcub_imagine_1739 .

Tomić, Branko, Gvozdenov, Maja, Cumbo, Marija, Dunjić Manevski, Sofija, Đorđević, Valentina, "Nasledni faktori rizika za trombofiliju – od tačkastih mutacija do primene veštačke inteligencije" in Treći kongres biologa Srbije (2022):278,
https://hdl.handle.net/21.15107/rcub_imagine_1739 .

TY  - JOUR
AU  - Kovač, Mirjana
AU  - Mitić, Gorana
AU  - Milenković, Marija
AU  - Basarić, Dusica
AU  - Tomić, Branko
AU  - Marković, Olivera
AU  - Zdravković, Marija
AU  - Ignjatović, Vera
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1516
AB  - Background: Coagulation dysfunction represents a serious complication in patients during the COVID-19 infec-tion, while fulminant thrombotic complications emerge as critical issues in individuals with severe COVID-19. In addition to a severe clinical presentation, comorbidities and age significantly contribute to the development of thrombotic complications in this disease. However, there is very little data on association of congenital thrombophilia and thrombotic events in the setting of COVID-19. Our study aimed to evaluate the risk of COVID-19 associated thrombosis in patients with congenital thrombophilia. Methods: This prospective, case-control study included patients with confirmed COVID-19 infection, followed 6 months post-confirmation. The final outcome was a symptomatic thrombotic event. In total, 90 COVID-19 pa-tients, 30 with known congenital thrombophilia and 60 patients without thrombophilia within the period July 2020-November 2021, were included in the study. Evaluation of hemostatic parameters including FVIII activity and D-dimer was performed for all patients at 1 month, 3 months and 6 months post-COVID-19 diagnosis. Results: Symptomatic thrombotic events were observed in 7 out of 30 (23 %) COVID-19 patients with throm-bophilia, and 12 out of 60 (20 %) without thrombophilia, P = 0.715. In addition, the two patient groups had comparable localization of thrombotic events, time to thrombotic event, effect of antithrombotic treatment and changes in FVIII activity, while D-dimer level were significantly increased in patients without thrombophilia. Conclusion: Our findings suggest that patients with congenital thrombophilia, irrespective of their age, a mild clinical picture and absence of comorbidities, should receive anticoagulant prophylaxis, adjusted based on the specific genetic defect.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Thrombosis Research
T1  - Thrombosis risk assessment in patients with congenital thrombophilia during COVID-19 infection
EP  - 156
SP  - 151
VL  - 218
DO  - 10.1016/j.thromres.2022.08.020
ER  - 

@article{
author = "Kovač, Mirjana and Mitić, Gorana and Milenković, Marija and Basarić, Dusica and Tomić, Branko and Marković, Olivera and Zdravković, Marija and Ignjatović, Vera",
year = "2022",
abstract = "Background: Coagulation dysfunction represents a serious complication in patients during the COVID-19 infec-tion, while fulminant thrombotic complications emerge as critical issues in individuals with severe COVID-19. In addition to a severe clinical presentation, comorbidities and age significantly contribute to the development of thrombotic complications in this disease. However, there is very little data on association of congenital thrombophilia and thrombotic events in the setting of COVID-19. Our study aimed to evaluate the risk of COVID-19 associated thrombosis in patients with congenital thrombophilia. Methods: This prospective, case-control study included patients with confirmed COVID-19 infection, followed 6 months post-confirmation. The final outcome was a symptomatic thrombotic event. In total, 90 COVID-19 pa-tients, 30 with known congenital thrombophilia and 60 patients without thrombophilia within the period July 2020-November 2021, were included in the study. Evaluation of hemostatic parameters including FVIII activity and D-dimer was performed for all patients at 1 month, 3 months and 6 months post-COVID-19 diagnosis. Results: Symptomatic thrombotic events were observed in 7 out of 30 (23 %) COVID-19 patients with throm-bophilia, and 12 out of 60 (20 %) without thrombophilia, P = 0.715. In addition, the two patient groups had comparable localization of thrombotic events, time to thrombotic event, effect of antithrombotic treatment and changes in FVIII activity, while D-dimer level were significantly increased in patients without thrombophilia. Conclusion: Our findings suggest that patients with congenital thrombophilia, irrespective of their age, a mild clinical picture and absence of comorbidities, should receive anticoagulant prophylaxis, adjusted based on the specific genetic defect.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Thrombosis Research",
title = "Thrombosis risk assessment in patients with congenital thrombophilia during COVID-19 infection",
pages = "156-151",
volume = "218",
doi = "10.1016/j.thromres.2022.08.020"
}

Kovač, M., Mitić, G., Milenković, M., Basarić, D., Tomić, B., Marković, O., Zdravković, M.,& Ignjatović, V.. (2022). Thrombosis risk assessment in patients with congenital thrombophilia during COVID-19 infection. in Thrombosis Research
Pergamon-Elsevier Science Ltd, Oxford., 218, 151-156.
https://doi.org/10.1016/j.thromres.2022.08.020

Kovač M, Mitić G, Milenković M, Basarić D, Tomić B, Marković O, Zdravković M, Ignjatović V. Thrombosis risk assessment in patients with congenital thrombophilia during COVID-19 infection. in Thrombosis Research. 2022;218:151-156.
doi:10.1016/j.thromres.2022.08.020 .

Kovač, Mirjana, Mitić, Gorana, Milenković, Marija, Basarić, Dusica, Tomić, Branko, Marković, Olivera, Zdravković, Marija, Ignjatović, Vera, "Thrombosis risk assessment in patients with congenital thrombophilia during COVID-19 infection" in Thrombosis Research, 218 (2022):151-156,
https://doi.org/10.1016/j.thromres.2022.08.020 . .

TY  - JOUR
AU  - Pruner, Iva
AU  - Dinčić, Evica
AU  - Gvozdenov, Maja
AU  - Tomić, Branko
AU  - Kovač, Mirjana
AU  - Đorđević, Valentina
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1646
AB  - Introduction. Ischemic stroke (IS) is a heterogeneous dis-order caused by several genetic and environmental risk factors. It was suggested that coagulation disorders cause 1-4% of cases with IS, especially in patients with early onset of IS. Case report. We describe a case of a young adult male who developed an unprovoked IS. Biochemical, immunological, and thrombophilia screening, as well as DNA sequencing, were performed in order to reveal molecular pathology underlying the stroke of the patient. Thrombophilia testing showed that patient was a homozygous carrier for PAI-1 4G/5G and MTHFR C677T mutations. Additional genetic analysis revealed the presence of the recently reported F2 c.1824C>T gene variant, located in the last exon of the pro-thrombin gene and has previously been shown to cause hy-perprothrombinemia, hypofibrinolysis, and altered fibrin clot phenotype. Conclusion. Our results suggest that the newly reported F2 c.1824C>T gene variant might have a synergistic effect with PAI 4G/4G and MTHFR 677TT genotype in the formation of altered fibrin clot phenotype characterized by thin, densely packed fibrin fibers, which makes clot less susceptible to fibrinolysis and greatly in-creases the risk for early ischemic stroke onset.
AB  - Ishemijski moždani udar (IMU) je heterogeni poremećaj
koji može biti uzrokovan genetskim faktorima rizika i faktorima
sredine. Poremećaji koagulacije mogu biti uzročnici u 1-4%
slučajeva IMU, naročito kod bolesnika kod kojih se IMU dogodi u
mlađem životnom dobu. Prikaz bolesnika. Prikazan je slučaj
bolesnika koji je u mlađem životnom dobu razvio IMU
nepoznatog uzroka. Urađeni su biohemijski, imunološki i testovi za
trombofiliju kao i sekvenciranje DNK sa ciljem da se utvrdi
molekularna patologija koja je mogla biti u osnovi moždanog udara
kod tog bolesnika. Testovima za trombofiliju utvrđeno je da je
bolesnik homozigotni nosilac mutacija PAI-1 4G/5G i MTHFR
C677T. Dodatnom genetičkom analizom otkriveno je prisustvo
nedavno opisane F2 c.1824C>T genske varijante, koja se nalazi u
poslednjem egzonu gena za protrombin i za koju je prethodno
pokazano da izaziva hiperprotrombinemiju, hipofibrinolizu i
izmenjeni fenotip fibrinskog ugruška. Zaključak. Naši rezultati
ukazuju na to da bi nova F2 c.1824C>T genska varijanta mogla
imati sinergistički efekat sa PAI 4G/4G i MTHFR 677TT
genotipom u nastanku fibrinskog ugruška sa izmenjenim
fenotipom, koji se odlikuje tankim, gusto upakovanim fibrinskim
vlaknima, što čini ugrušak manje podložnim fibrinolizi i povećava
rizik od nastanka IMU u ranijem životnom dobu.
T2  - Vojnosanitetski pregled
T2  - Vojnosanitetski pregled
T1  - Early-onset ischaemic stroke in a patient with the novel F2 c.1824C>T gene variant and PAI-1 4G/4G, MTHFR 677TT genotype
EP  - 1043
IS  - 10
SP  - 1039
VL  - 79
DO  - doi.org/10.2298/VSP210323066P
ER  - 

@article{
author = "Pruner, Iva and Dinčić, Evica and Gvozdenov, Maja and Tomić, Branko and Kovač, Mirjana and Đorđević, Valentina",
year = "2022",
abstract = "Introduction. Ischemic stroke (IS) is a heterogeneous dis-order caused by several genetic and environmental risk factors. It was suggested that coagulation disorders cause 1-4% of cases with IS, especially in patients with early onset of IS. Case report. We describe a case of a young adult male who developed an unprovoked IS. Biochemical, immunological, and thrombophilia screening, as well as DNA sequencing, were performed in order to reveal molecular pathology underlying the stroke of the patient. Thrombophilia testing showed that patient was a homozygous carrier for PAI-1 4G/5G and MTHFR C677T mutations. Additional genetic analysis revealed the presence of the recently reported F2 c.1824C>T gene variant, located in the last exon of the pro-thrombin gene and has previously been shown to cause hy-perprothrombinemia, hypofibrinolysis, and altered fibrin clot phenotype. Conclusion. Our results suggest that the newly reported F2 c.1824C>T gene variant might have a synergistic effect with PAI 4G/4G and MTHFR 677TT genotype in the formation of altered fibrin clot phenotype characterized by thin, densely packed fibrin fibers, which makes clot less susceptible to fibrinolysis and greatly in-creases the risk for early ischemic stroke onset., Ishemijski moždani udar (IMU) je heterogeni poremećaj
koji može biti uzrokovan genetskim faktorima rizika i faktorima
sredine. Poremećaji koagulacije mogu biti uzročnici u 1-4%
slučajeva IMU, naročito kod bolesnika kod kojih se IMU dogodi u
mlađem životnom dobu. Prikaz bolesnika. Prikazan je slučaj
bolesnika koji je u mlađem životnom dobu razvio IMU
nepoznatog uzroka. Urađeni su biohemijski, imunološki i testovi za
trombofiliju kao i sekvenciranje DNK sa ciljem da se utvrdi
molekularna patologija koja je mogla biti u osnovi moždanog udara
kod tog bolesnika. Testovima za trombofiliju utvrđeno je da je
bolesnik homozigotni nosilac mutacija PAI-1 4G/5G i MTHFR
C677T. Dodatnom genetičkom analizom otkriveno je prisustvo
nedavno opisane F2 c.1824C>T genske varijante, koja se nalazi u
poslednjem egzonu gena za protrombin i za koju je prethodno
pokazano da izaziva hiperprotrombinemiju, hipofibrinolizu i
izmenjeni fenotip fibrinskog ugruška. Zaključak. Naši rezultati
ukazuju na to da bi nova F2 c.1824C>T genska varijanta mogla
imati sinergistički efekat sa PAI 4G/4G i MTHFR 677TT
genotipom u nastanku fibrinskog ugruška sa izmenjenim
fenotipom, koji se odlikuje tankim, gusto upakovanim fibrinskim
vlaknima, što čini ugrušak manje podložnim fibrinolizi i povećava
rizik od nastanka IMU u ranijem životnom dobu.",
journal = "Vojnosanitetski pregled, Vojnosanitetski pregled",
title = "Early-onset ischaemic stroke in a patient with the novel F2 c.1824C>T gene variant and PAI-1 4G/4G, MTHFR 677TT genotype",
pages = "1043-1039",
number = "10",
volume = "79",
doi = "doi.org/10.2298/VSP210323066P"
}

Pruner, I., Dinčić, E., Gvozdenov, M., Tomić, B., Kovač, M.,& Đorđević, V.. (2022). Early-onset ischaemic stroke in a patient with the novel F2 c.1824C>T gene variant and PAI-1 4G/4G, MTHFR 677TT genotype. in Vojnosanitetski pregled, 79(10), 1039-1043.
https://doi.org/doi.org/10.2298/VSP210323066P

Pruner I, Dinčić E, Gvozdenov M, Tomić B, Kovač M, Đorđević V. Early-onset ischaemic stroke in a patient with the novel F2 c.1824C>T gene variant and PAI-1 4G/4G, MTHFR 677TT genotype. in Vojnosanitetski pregled. 2022;79(10):1039-1043.
doi:doi.org/10.2298/VSP210323066P .

Pruner, Iva, Dinčić, Evica, Gvozdenov, Maja, Tomić, Branko, Kovač, Mirjana, Đorđević, Valentina, "Early-onset ischaemic stroke in a patient with the novel F2 c.1824C>T gene variant and PAI-1 4G/4G, MTHFR 677TT genotype" in Vojnosanitetski pregled, 79, no. 10 (2022):1039-1043,
https://doi.org/doi.org/10.2298/VSP210323066P . .

TY  - JOUR
AU  - Kovač, Mirjana
AU  - Erić, Bojana
AU  - Stojneva-Istatkov, Jelena
AU  - Lukić, Vojislav
AU  - Milić, Ana
AU  - Vukičević, Dragana
AU  - Orlić, Dušan
AU  - Tomić, Branko
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1412
AB  - Uvod/Cilj. Određivanje nivoa hemoglobin (Hb) je rutinski deo selekcije dobrovoljnih davalaca krvi. Prethodno publikovane studije pokazale su da se nedostatak gvožđa javlja kod redovnih davalaca krvi. Cilj ove prospektivne studije je bio da se utvrdi status gvožđa kod davalaca kod kojih je pre davanja utvrđen nizak nivo Hb i da se proceni stepen korelacije kapilarnih metoda, sa referentnom metodom određivanja Hb iz venske krvi, kao i sa i nivoom feritina. Metode. U periodu od februara 2017. do decembra 2018. godine, bilo je uključeno 200 dobrovoljnih davalaca sa niskim nivoima Hb, starosne dobi 19-64 godine (medijana 39 godina). Hb je određivan primenom metode bakar sulfat, kapilarnom metodom "HemoCue", i iz venske krvi u sklopu određivanja kompletne krvne slike (KKS). Nivo feritina određivan je primenom turbodimetrijske metode. Rezultati. Nizak nivo feritina utvrđen je kod 42,7% muškaraca i 57,3% žena (p = 0,008). U odnosu na nivo feritina  lt  12 mg/L, odnosno  gt  50 mg/L, zabeležena je značajna razlika između polova (p = 0,023, odnosno p = 0,022). Poređenje vrednosti Hb dobijenih kapilarnim metodama u odnosu na referentne vrednosti Hb, određene iz KKS, pokazalo je da metoda s bakar sulfatom daje lažno niske vrednosti Hb kod 10,5% slučajeva (p  lt  0,001). Vrednosti Hb dobijene metodom "HemoCue-a" značajno su korelirale sa vrednostima Hb iz KKS, dok korelacija između nivoa feritina i Hb, određenog pomoću obe kapilarne metode, nije uočena. Zaključak. Kod 51,5% naših davalaca krvi koji su vraćeni zbog niskih vrednosti Hb utvrđen je snižen nivo feritina. Na osnovu ovih rezultata neophodno je odrediti algoritam za detekciju nedostatka gvožđa, dok je kapilarna metoda (HemoCue) pogodnija metoda za testiranje Hb pre davanja krvi.
AB  - Background/Aim. Haemoglobin (Hb) determination is a routine part of the blood donor selection process. Previously reported studies have revealed that iron deficiency is common in frequent donors. This prospective investigation was aimed at examining iron status among blood donors with low circulating Hb and evaluating correlation between Hb values determined by capillary methods and those obtained by reference method from venous blood count (BC), as well as ferritin level. Methods. Between February 2017 and December 2018, 200 consecutively recruited regular blood donors with low Hb, aged 19 to 64 years (median 39), were included. Hb level was determined using the copper sulphate method, the HemoCue capillary method, and also from venous blood within the complete blood count (CBC) test. Plasma ferritin was determined turbidimetrically. Results. In 42.7% of men and 57.3% of women, ferritin concentration was low (p = 0.008). The relative numbers of males and females, with levels  lt  12 mg/L (p = 0.023) or  gt  50 mg/L (p = 0.022), differed. Comparison of the values obtained with the capillary methods with reference Hb levels obtained from the CBC test showed that the copper sulphate procedure gave false fails in 10.5% of cases (p  lt  0.001). Hb values from HemoCue were significantly correlated with Hb values from the CBC test, but no correlation was observed between ferritin levels and Hb levels determined by both capillary method. Conclusion. Low ferritin was observed in 51.5% of Serbian blood donors deferred due to low Hb. Based on our results, the determination of the algorithm in the iron deficiency detection is necessary, while the capillary method (HemoCue) represents a more convenient method for Hb testing prior to blood donation.
PB  - Vojnomedicinska akademija - Institut za naučne informacije, Beograd
T2  - Vojnosanitetski pregled
T1  - Ispitivanje statusa gvožđa kod davalaca krvi vraćenih zbog niskog nivoa hemoglobina
T1  - Iron status among blood donors deferred due to low haemoglobin level
EP  - 206
IS  - 2
SP  - 202
VL  - 78
DO  - 10.2298/VSP190327063K
ER  - 

@article{
author = "Kovač, Mirjana and Erić, Bojana and Stojneva-Istatkov, Jelena and Lukić, Vojislav and Milić, Ana and Vukičević, Dragana and Orlić, Dušan and Tomić, Branko",
year = "2021",
abstract = "Uvod/Cilj. Određivanje nivoa hemoglobin (Hb) je rutinski deo selekcije dobrovoljnih davalaca krvi. Prethodno publikovane studije pokazale su da se nedostatak gvožđa javlja kod redovnih davalaca krvi. Cilj ove prospektivne studije je bio da se utvrdi status gvožđa kod davalaca kod kojih je pre davanja utvrđen nizak nivo Hb i da se proceni stepen korelacije kapilarnih metoda, sa referentnom metodom određivanja Hb iz venske krvi, kao i sa i nivoom feritina. Metode. U periodu od februara 2017. do decembra 2018. godine, bilo je uključeno 200 dobrovoljnih davalaca sa niskim nivoima Hb, starosne dobi 19-64 godine (medijana 39 godina). Hb je određivan primenom metode bakar sulfat, kapilarnom metodom "HemoCue", i iz venske krvi u sklopu određivanja kompletne krvne slike (KKS). Nivo feritina određivan je primenom turbodimetrijske metode. Rezultati. Nizak nivo feritina utvrđen je kod 42,7% muškaraca i 57,3% žena (p = 0,008). U odnosu na nivo feritina  lt  12 mg/L, odnosno  gt  50 mg/L, zabeležena je značajna razlika između polova (p = 0,023, odnosno p = 0,022). Poređenje vrednosti Hb dobijenih kapilarnim metodama u odnosu na referentne vrednosti Hb, određene iz KKS, pokazalo je da metoda s bakar sulfatom daje lažno niske vrednosti Hb kod 10,5% slučajeva (p  lt  0,001). Vrednosti Hb dobijene metodom "HemoCue-a" značajno su korelirale sa vrednostima Hb iz KKS, dok korelacija između nivoa feritina i Hb, određenog pomoću obe kapilarne metode, nije uočena. Zaključak. Kod 51,5% naših davalaca krvi koji su vraćeni zbog niskih vrednosti Hb utvrđen je snižen nivo feritina. Na osnovu ovih rezultata neophodno je odrediti algoritam za detekciju nedostatka gvožđa, dok je kapilarna metoda (HemoCue) pogodnija metoda za testiranje Hb pre davanja krvi., Background/Aim. Haemoglobin (Hb) determination is a routine part of the blood donor selection process. Previously reported studies have revealed that iron deficiency is common in frequent donors. This prospective investigation was aimed at examining iron status among blood donors with low circulating Hb and evaluating correlation between Hb values determined by capillary methods and those obtained by reference method from venous blood count (BC), as well as ferritin level. Methods. Between February 2017 and December 2018, 200 consecutively recruited regular blood donors with low Hb, aged 19 to 64 years (median 39), were included. Hb level was determined using the copper sulphate method, the HemoCue capillary method, and also from venous blood within the complete blood count (CBC) test. Plasma ferritin was determined turbidimetrically. Results. In 42.7% of men and 57.3% of women, ferritin concentration was low (p = 0.008). The relative numbers of males and females, with levels  lt  12 mg/L (p = 0.023) or  gt  50 mg/L (p = 0.022), differed. Comparison of the values obtained with the capillary methods with reference Hb levels obtained from the CBC test showed that the copper sulphate procedure gave false fails in 10.5% of cases (p  lt  0.001). Hb values from HemoCue were significantly correlated with Hb values from the CBC test, but no correlation was observed between ferritin levels and Hb levels determined by both capillary method. Conclusion. Low ferritin was observed in 51.5% of Serbian blood donors deferred due to low Hb. Based on our results, the determination of the algorithm in the iron deficiency detection is necessary, while the capillary method (HemoCue) represents a more convenient method for Hb testing prior to blood donation.",
publisher = "Vojnomedicinska akademija - Institut za naučne informacije, Beograd",
journal = "Vojnosanitetski pregled",
title = "Ispitivanje statusa gvožđa kod davalaca krvi vraćenih zbog niskog nivoa hemoglobina, Iron status among blood donors deferred due to low haemoglobin level",
pages = "206-202",
number = "2",
volume = "78",
doi = "10.2298/VSP190327063K"
}

Kovač, M., Erić, B., Stojneva-Istatkov, J., Lukić, V., Milić, A., Vukičević, D., Orlić, D.,& Tomić, B.. (2021). Ispitivanje statusa gvožđa kod davalaca krvi vraćenih zbog niskog nivoa hemoglobina. in Vojnosanitetski pregled
Vojnomedicinska akademija - Institut za naučne informacije, Beograd., 78(2), 202-206.
https://doi.org/10.2298/VSP190327063K

Kovač M, Erić B, Stojneva-Istatkov J, Lukić V, Milić A, Vukičević D, Orlić D, Tomić B. Ispitivanje statusa gvožđa kod davalaca krvi vraćenih zbog niskog nivoa hemoglobina. in Vojnosanitetski pregled. 2021;78(2):202-206.
doi:10.2298/VSP190327063K .

Kovač, Mirjana, Erić, Bojana, Stojneva-Istatkov, Jelena, Lukić, Vojislav, Milić, Ana, Vukičević, Dragana, Orlić, Dušan, Tomić, Branko, "Ispitivanje statusa gvožđa kod davalaca krvi vraćenih zbog niskog nivoa hemoglobina" in Vojnosanitetski pregled, 78, no. 2 (2021):202-206,
https://doi.org/10.2298/VSP190327063K . .

TY  - CONF
AU  - Dunjić, Sofija
AU  - Cumbo, Marija
AU  - Gvozdenov, Maja
AU  - Taxiarchis, Apostolos
AU  - Tomić, Branko
AU  - Antović, Jovan
AU  - Đorđević, Valentina
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1635
AB  - Prothrombin Belgrade mutation is a result of the c.1787G>T
mutation in the prothrombin gene, which leads to the substitution of
Arg596 by Gln. This mutation is located in the antithrombin binding site
and leads to the impaired inactivation of thrombin by antithrombin and
antithrombin resistance, resulting in a thrombotic phenotype. Previous
studies have shown the complex mechanism of this mutation, manifested with higher endogenous thrombin potential, lower prothrombin
activity with normal prothrombin levels in carriers’ plasma.
C3  - Research and Practice in Thrombosis and Haemostasis
C3  - Research and Practice in Thrombosis and Haemostasis
T1  - The prothrombin Belgrade mutation causing antithrombin resistance does not affect fibrin clot formation
EP  - 1117
IS  - 1
SP  - 1117
VL  - 4
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1635
ER  - 

@conference{
author = "Dunjić, Sofija and Cumbo, Marija and Gvozdenov, Maja and Taxiarchis, Apostolos and Tomić, Branko and Antović, Jovan and Đorđević, Valentina",
year = "2020",
abstract = "Prothrombin Belgrade mutation is a result of the c.1787G>T
mutation in the prothrombin gene, which leads to the substitution of
Arg596 by Gln. This mutation is located in the antithrombin binding site
and leads to the impaired inactivation of thrombin by antithrombin and
antithrombin resistance, resulting in a thrombotic phenotype. Previous
studies have shown the complex mechanism of this mutation, manifested with higher endogenous thrombin potential, lower prothrombin
activity with normal prothrombin levels in carriers’ plasma.",
journal = "Research and Practice in Thrombosis and Haemostasis, Research and Practice in Thrombosis and Haemostasis",
title = "The prothrombin Belgrade mutation causing antithrombin resistance does not affect fibrin clot formation",
pages = "1117-1117",
number = "1",
volume = "4",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1635"
}

Dunjić, S., Cumbo, M., Gvozdenov, M., Taxiarchis, A., Tomić, B., Antović, J.,& Đorđević, V.. (2020). The prothrombin Belgrade mutation causing antithrombin resistance does not affect fibrin clot formation. in Research and Practice in Thrombosis and Haemostasis, 4(1), 1117-1117.
https://hdl.handle.net/21.15107/rcub_imagine_1635

Dunjić S, Cumbo M, Gvozdenov M, Taxiarchis A, Tomić B, Antović J, Đorđević V. The prothrombin Belgrade mutation causing antithrombin resistance does not affect fibrin clot formation. in Research and Practice in Thrombosis and Haemostasis. 2020;4(1):1117-1117.
https://hdl.handle.net/21.15107/rcub_imagine_1635 .

Dunjić, Sofija, Cumbo, Marija, Gvozdenov, Maja, Taxiarchis, Apostolos, Tomić, Branko, Antović, Jovan, Đorđević, Valentina, "The prothrombin Belgrade mutation causing antithrombin resistance does not affect fibrin clot formation" in Research and Practice in Thrombosis and Haemostasis, 4, no. 1 (2020):1117-1117,
https://hdl.handle.net/21.15107/rcub_imagine_1635 .

TY  - JOUR
AU  - Pruner, Iva
AU  - Farm, Maria
AU  - Tomić, Branko
AU  - Gvozdenov, Maja
AU  - Kovač, Mirjana
AU  - Miljić, Predrag
AU  - Soutari, Nida Mahmoud Hourani
AU  - Antović, Aleksandra
AU  - Radojković, Dragica
AU  - Antović, Jovan P.
AU  - Đorđević, Valentina
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1375
AB  - BACKGROUND: Thrombosis is a major global disease burden with almost 60% of cases related to underlying heredity and most cases still idiopathic. Synonymous single nucleotide polymorphisms (sSNPs) are considered silent and phenotypically neutral. Our previous study revealed a novel synonymous FII c.1824C gt  T variant as a potential risk factor for pregnancy loss, but it has not yet been associated with thrombotic diseases. METHODS: To determine the frequency of the FII c.1824C gt  T variant we have sequenced patients' DNA. Prothrombin RNA expression was measured by quantitative PCR. Functional analyses included routine hemostasis tests, western blotting and ELISA to determine prothrombin levels in plasma, and global hemostasis assays for thrombin and fibrin generation in carriers of the FII c.1824C gt  T variant. Scanning electron mi- croscopy was used to examine the structure of fibrin clots. RESULTS: Frequency of the FII c.1824C gt  T variant was significantly increased in patients with venous thromboembolism and cerebrovascular insult. Examination in vitro demonstrated increased expression of prothrombin mRNA in FII c.1824C gt  T transfected cells. Our ex vivo study of FII c.1824C gt  T carriers showed that the presence of this variant was associated with hyperprothrom-binemia, hypofibrinolysis, and formation of densely packed fibrin clots resistant to fibrinolysis. CONCLUSION: Our data indicate that FII c.1824C gt  T, although a synonymous variant, leads to the development of a prothrombotic phenotype and could represent a new prothrombotic risk factor. As a silent variant, FII c.1824C gt  T would probably be overlooked during genetic screening, and our results show that it could not be detected in routine laboratory tests.
PB  - Oxford Univ Press Inc, Cary
T2  - Clinical Chemistry
T1  - The Silence Speaks, but We Do Not Listen: Synonymous c.1824C  gt  T Gene Variant in the Last Exon of the Prothrombin Gene as a New Prothrombotic Risk Factor
EP  - 389
IS  - 2
SP  - 379
VL  - 66
DO  - 10.1093/clinchem/hvz015
ER  - 

@article{
author = "Pruner, Iva and Farm, Maria and Tomić, Branko and Gvozdenov, Maja and Kovač, Mirjana and Miljić, Predrag and Soutari, Nida Mahmoud Hourani and Antović, Aleksandra and Radojković, Dragica and Antović, Jovan P. and Đorđević, Valentina",
year = "2020",
abstract = "BACKGROUND: Thrombosis is a major global disease burden with almost 60% of cases related to underlying heredity and most cases still idiopathic. Synonymous single nucleotide polymorphisms (sSNPs) are considered silent and phenotypically neutral. Our previous study revealed a novel synonymous FII c.1824C gt  T variant as a potential risk factor for pregnancy loss, but it has not yet been associated with thrombotic diseases. METHODS: To determine the frequency of the FII c.1824C gt  T variant we have sequenced patients' DNA. Prothrombin RNA expression was measured by quantitative PCR. Functional analyses included routine hemostasis tests, western blotting and ELISA to determine prothrombin levels in plasma, and global hemostasis assays for thrombin and fibrin generation in carriers of the FII c.1824C gt  T variant. Scanning electron mi- croscopy was used to examine the structure of fibrin clots. RESULTS: Frequency of the FII c.1824C gt  T variant was significantly increased in patients with venous thromboembolism and cerebrovascular insult. Examination in vitro demonstrated increased expression of prothrombin mRNA in FII c.1824C gt  T transfected cells. Our ex vivo study of FII c.1824C gt  T carriers showed that the presence of this variant was associated with hyperprothrom-binemia, hypofibrinolysis, and formation of densely packed fibrin clots resistant to fibrinolysis. CONCLUSION: Our data indicate that FII c.1824C gt  T, although a synonymous variant, leads to the development of a prothrombotic phenotype and could represent a new prothrombotic risk factor. As a silent variant, FII c.1824C gt  T would probably be overlooked during genetic screening, and our results show that it could not be detected in routine laboratory tests.",
publisher = "Oxford Univ Press Inc, Cary",
journal = "Clinical Chemistry",
title = "The Silence Speaks, but We Do Not Listen: Synonymous c.1824C  gt  T Gene Variant in the Last Exon of the Prothrombin Gene as a New Prothrombotic Risk Factor",
pages = "389-379",
number = "2",
volume = "66",
doi = "10.1093/clinchem/hvz015"
}

Pruner, I., Farm, M., Tomić, B., Gvozdenov, M., Kovač, M., Miljić, P., Soutari, N. M. H., Antović, A., Radojković, D., Antović, J. P.,& Đorđević, V.. (2020). The Silence Speaks, but We Do Not Listen: Synonymous c.1824C  gt  T Gene Variant in the Last Exon of the Prothrombin Gene as a New Prothrombotic Risk Factor. in Clinical Chemistry
Oxford Univ Press Inc, Cary., 66(2), 379-389.
https://doi.org/10.1093/clinchem/hvz015

Pruner I, Farm M, Tomić B, Gvozdenov M, Kovač M, Miljić P, Soutari NMH, Antović A, Radojković D, Antović JP, Đorđević V. The Silence Speaks, but We Do Not Listen: Synonymous c.1824C  gt  T Gene Variant in the Last Exon of the Prothrombin Gene as a New Prothrombotic Risk Factor. in Clinical Chemistry. 2020;66(2):379-389.
doi:10.1093/clinchem/hvz015 .

Pruner, Iva, Farm, Maria, Tomić, Branko, Gvozdenov, Maja, Kovač, Mirjana, Miljić, Predrag, Soutari, Nida Mahmoud Hourani, Antović, Aleksandra, Radojković, Dragica, Antović, Jovan P., Đorđević, Valentina, "The Silence Speaks, but We Do Not Listen: Synonymous c.1824C  gt  T Gene Variant in the Last Exon of the Prothrombin Gene as a New Prothrombotic Risk Factor" in Clinical Chemistry, 66, no. 2 (2020):379-389,
https://doi.org/10.1093/clinchem/hvz015 . .

TY  - CONF
AU  - Kovač, M.
AU  - Basarić, D.
AU  - Tomić, Branko
AU  - Backović, D.
AU  - Lalić Cosić, S.
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1636
UR  - https://abstracts.isth.org/abstract/influence-of-doac-remove-on-coagulation-assays-during-thrombophilia-testing-in-patients-treated-with-rivaroxaban-or-dabigatran/
AB  - Background: Direct oral anticoagulants (DOAC) are increasingly being used as an alternative to warfarin in the treatment of venous thromboembolism. DOAC administration has a significant impact on coagulation assays. This is especially important during thrombophilia testing.

Aims: To evaluate the effect of DOAC Remove on coagulation assays during thrombophilia testing in patients treated with DOAC.

Methods: We have used samples from 20 patients treated with DOAC. Two samples of venous blood on sodium citrate were taken for each patient. One was prepared by standard method for coagulation assays, while, the second one was prepared using DOAC Remove. According to the instruction the samples were mixed gently for 5 minutes with DOAC Remove tablet, and then centrifuged 2 minutes on 2000g. The supernatant after centrifugation is used to the coagulation assays. So prepared samples were used in the thrombophilia testing.

Results: Before DOAC Remove in 10 patients treated with Rivaroxaban average APTT of 31.5s; PT 104%; LA1 51.7s; LA2 40.3s; LA- R 1.28, AT 104%, PC 104%, PS 87% and APC-R 4.1 were obtained. In Dabigatran patients APTT 40.5s, PT 104%; LA1 73.7s; LA2 53.7s; LA-R 1.37, AT 103% PC 98% and PS 82% were obtained. In relation to the APC-R test, in half of the investigated patients no result for APC-R was obtained, while, for the rest, average APC-R of 6.5 were obtained. After DOAC Remove in Rivaroxaban patients APTT 29.7s; PT 110%; LA1 37.3s; LA2 33.8s; LA- R 1.12, AT 96%, PC 102%, PS 88% and APCR 4.2 were recorded. In Dabigatran patients APTT 28.1s, PT 117%; LA 39.1s; LA2 33.8s; LA-R 1.15, AT 104%, PC 97.5%, PS 84.5% and APC-R 6.5 were recorded.

Conclusions: DOAC was practically inactivated after the addition of the DOAC Remove, which made it possible to perform analyzes for the LA and APC-R testing freely and obtain relevant results.
PB  - John Wiley & Sons
C3  - ISTH 2020 Congress
T1  - Influence of DOAC Remove on Coagulation Assays During Thrombophilia Testing in Patients Treated with Rivaroxaban or Dabigatran
SP  - PB0633
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1636
ER  - 

@conference{
author = "Kovač, M. and Basarić, D. and Tomić, Branko and Backović, D. and Lalić Cosić, S.",
year = "2020",
abstract = "Background: Direct oral anticoagulants (DOAC) are increasingly being used as an alternative to warfarin in the treatment of venous thromboembolism. DOAC administration has a significant impact on coagulation assays. This is especially important during thrombophilia testing.

Aims: To evaluate the effect of DOAC Remove on coagulation assays during thrombophilia testing in patients treated with DOAC.

Methods: We have used samples from 20 patients treated with DOAC. Two samples of venous blood on sodium citrate were taken for each patient. One was prepared by standard method for coagulation assays, while, the second one was prepared using DOAC Remove. According to the instruction the samples were mixed gently for 5 minutes with DOAC Remove tablet, and then centrifuged 2 minutes on 2000g. The supernatant after centrifugation is used to the coagulation assays. So prepared samples were used in the thrombophilia testing.

Results: Before DOAC Remove in 10 patients treated with Rivaroxaban average APTT of 31.5s; PT 104%; LA1 51.7s; LA2 40.3s; LA- R 1.28, AT 104%, PC 104%, PS 87% and APC-R 4.1 were obtained. In Dabigatran patients APTT 40.5s, PT 104%; LA1 73.7s; LA2 53.7s; LA-R 1.37, AT 103% PC 98% and PS 82% were obtained. In relation to the APC-R test, in half of the investigated patients no result for APC-R was obtained, while, for the rest, average APC-R of 6.5 were obtained. After DOAC Remove in Rivaroxaban patients APTT 29.7s; PT 110%; LA1 37.3s; LA2 33.8s; LA- R 1.12, AT 96%, PC 102%, PS 88% and APCR 4.2 were recorded. In Dabigatran patients APTT 28.1s, PT 117%; LA 39.1s; LA2 33.8s; LA-R 1.15, AT 104%, PC 97.5%, PS 84.5% and APC-R 6.5 were recorded.

Conclusions: DOAC was practically inactivated after the addition of the DOAC Remove, which made it possible to perform analyzes for the LA and APC-R testing freely and obtain relevant results.",
publisher = "John Wiley & Sons",
journal = "ISTH 2020 Congress",
title = "Influence of DOAC Remove on Coagulation Assays During Thrombophilia Testing in Patients Treated with Rivaroxaban or Dabigatran",
pages = "PB0633",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1636"
}

Kovač, M., Basarić, D., Tomić, B., Backović, D.,& Lalić Cosić, S.. (2020). Influence of DOAC Remove on Coagulation Assays During Thrombophilia Testing in Patients Treated with Rivaroxaban or Dabigatran. in ISTH 2020 Congress
John Wiley & Sons., PB0633.
https://hdl.handle.net/21.15107/rcub_imagine_1636

Kovač M, Basarić D, Tomić B, Backović D, Lalić Cosić S. Influence of DOAC Remove on Coagulation Assays During Thrombophilia Testing in Patients Treated with Rivaroxaban or Dabigatran. in ISTH 2020 Congress. 2020;:PB0633.
https://hdl.handle.net/21.15107/rcub_imagine_1636 .

Kovač, M., Basarić, D., Tomić, Branko, Backović, D., Lalić Cosić, S., "Influence of DOAC Remove on Coagulation Assays During Thrombophilia Testing in Patients Treated with Rivaroxaban or Dabigatran" in ISTH 2020 Congress (2020):PB0633,
https://hdl.handle.net/21.15107/rcub_imagine_1636 .

TY  - CONF
AU  - Tomić, Branko
AU  - Kovač, Mirjana
AU  - Pruner, Iva
AU  - Gvozdenov, Maja
AU  - Dunjić, Sofija
AU  - Cumbo, Marija
AU  - Radojković, Dragica
AU  - Đorđević, Valentina
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2145
AB  - PURPOSE: Thrombosis is multicausal disease in which both acquired and genetic risk factors play
important roles. The most frequent genetic risk factors known to date are the Factor V G1691A (FV
Leiden) and FII G20210A mutations. On the other hand, inherited antithrombin (AT) deficiency, caused
by mutations in the AT gene (SERPINC1) is a very rare disorder, but it is associated with significant risk
for thrombotic complications. AT deficiency is classified into two types: type-I is a quantitative disorder
characterized by decreased amount and activity of AT, while type-II is a qualitative - functional disorder.
Aim of our study was to analyze the frequency of FV Leiden and FII G20210A mutations in patients with
inherited AT deficiency from Serbia.
METHODOLOGY: A study was carried out in large group of AT deficiency patients from Serbia. Cohort
of 42 subjects (15m/27f; 36.7±18.7y) from 18 Serbian families included 24 symptomatic and 18
asymptomatic first-degree relatives. Among them, type-I AT deficiency were detected in 9 families (19
members: 6m/13f; 37.1±19.0y) and type-II in 9 families (23 members: 9m/14f; 36.5±18.8y). FV Leiden
and FII G2010A mutations were detected by PCR, followed by digestion with specific restriction enzymes
(PCR-RFLP).
RESULTS: We have detected 3 FV Leiden heterozygous carriers in 3 different families (1 with type-I
and 2 with type-II AT deficiency). All 3 carriers were symptomatic. Regarding FII G20210A mutation, 2
heterozygous carriers, both asymptomatic and from same family with type-I deficiency, were identified.
According to our findings in families with AT deficiency from Serbia frequency of FV Leiden and FII
G20210A mutation are 16.7% and 5.6%, respectively.
CONCLUSION: This is the first study in which frequency of FV Leiden and FII G20210A mutations in
patients with inherited AT deficiency from Serbia were examined. Results of our study suggest that
these mutations can be relevant for AT deficiency patients’ phenotype, but further studies are required.
C3  - 16th International  Hemophilia Congress of Turkey
T1  - Frequency of FV Leiden and FII G20210A Mutations in Patients with Inherited Antithrombin Deficiency from Serbia
EP  - 212
SP  - 212
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2145
ER  - 

@conference{
author = "Tomić, Branko and Kovač, Mirjana and Pruner, Iva and Gvozdenov, Maja and Dunjić, Sofija and Cumbo, Marija and Radojković, Dragica and Đorđević, Valentina",
year = "2019",
abstract = "PURPOSE: Thrombosis is multicausal disease in which both acquired and genetic risk factors play
important roles. The most frequent genetic risk factors known to date are the Factor V G1691A (FV
Leiden) and FII G20210A mutations. On the other hand, inherited antithrombin (AT) deficiency, caused
by mutations in the AT gene (SERPINC1) is a very rare disorder, but it is associated with significant risk
for thrombotic complications. AT deficiency is classified into two types: type-I is a quantitative disorder
characterized by decreased amount and activity of AT, while type-II is a qualitative - functional disorder.
Aim of our study was to analyze the frequency of FV Leiden and FII G20210A mutations in patients with
inherited AT deficiency from Serbia.
METHODOLOGY: A study was carried out in large group of AT deficiency patients from Serbia. Cohort
of 42 subjects (15m/27f; 36.7±18.7y) from 18 Serbian families included 24 symptomatic and 18
asymptomatic first-degree relatives. Among them, type-I AT deficiency were detected in 9 families (19
members: 6m/13f; 37.1±19.0y) and type-II in 9 families (23 members: 9m/14f; 36.5±18.8y). FV Leiden
and FII G2010A mutations were detected by PCR, followed by digestion with specific restriction enzymes
(PCR-RFLP).
RESULTS: We have detected 3 FV Leiden heterozygous carriers in 3 different families (1 with type-I
and 2 with type-II AT deficiency). All 3 carriers were symptomatic. Regarding FII G20210A mutation, 2
heterozygous carriers, both asymptomatic and from same family with type-I deficiency, were identified.
According to our findings in families with AT deficiency from Serbia frequency of FV Leiden and FII
G20210A mutation are 16.7% and 5.6%, respectively.
CONCLUSION: This is the first study in which frequency of FV Leiden and FII G20210A mutations in
patients with inherited AT deficiency from Serbia were examined. Results of our study suggest that
these mutations can be relevant for AT deficiency patients’ phenotype, but further studies are required.",
journal = "16th International  Hemophilia Congress of Turkey",
title = "Frequency of FV Leiden and FII G20210A Mutations in Patients with Inherited Antithrombin Deficiency from Serbia",
pages = "212-212",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2145"
}

Tomić, B., Kovač, M., Pruner, I., Gvozdenov, M., Dunjić, S., Cumbo, M., Radojković, D.,& Đorđević, V.. (2019). Frequency of FV Leiden and FII G20210A Mutations in Patients with Inherited Antithrombin Deficiency from Serbia. in 16th International  Hemophilia Congress of Turkey, 212-212.
https://hdl.handle.net/21.15107/rcub_imagine_2145

Tomić B, Kovač M, Pruner I, Gvozdenov M, Dunjić S, Cumbo M, Radojković D, Đorđević V. Frequency of FV Leiden and FII G20210A Mutations in Patients with Inherited Antithrombin Deficiency from Serbia. in 16th International  Hemophilia Congress of Turkey. 2019;:212-212.
https://hdl.handle.net/21.15107/rcub_imagine_2145 .

Tomić, Branko, Kovač, Mirjana, Pruner, Iva, Gvozdenov, Maja, Dunjić, Sofija, Cumbo, Marija, Radojković, Dragica, Đorđević, Valentina, "Frequency of FV Leiden and FII G20210A Mutations in Patients with Inherited Antithrombin Deficiency from Serbia" in 16th International  Hemophilia Congress of Turkey (2019):212-212,
https://hdl.handle.net/21.15107/rcub_imagine_2145 .

TY  - JOUR
AU  - Cumbo, Marija
AU  - Tomić, Branko
AU  - Dunjić Manevski, Sofija
AU  - Jovanović, Tamara
AU  - Gvozdenov, Maja
AU  - Pruner, Iva
AU  - Aralica, Gorana
AU  - Kapitanović, Sanja
AU  - Cacev, Tamara
AU  - Đorđević, Valentina
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1219
AB  - Background/ Aim: Thrombin plays significant roles in various types of cancer. However, the expression levels of prothrombin, the thrombin precursor, in cancer remain unclear. Variants of the 3'end of the prothrombin gene lead to increased prothrombin expression. This study aimed to analyze prothrombin 3'end gene variants in colon tumor and adjacent normal tissue samples. Materials and Methods: The study group consisted of 93 patients suffering from colon adenocarcinoma. The 3'end of the prothrombin gene was analyzed by DNA sequencing. Results: Three variants, all previously associated with increased prothrombin expression were detected. Frequency of the FII 19911G allele was 46.77% and 47.85% in tumor and normal tissue, respectively. For the FII 20210A allele, the detected frequencies were 2.15% and 1.61%, respectively. The frequency of the FII c.1824T allele was 0.54% in both tissues. Four patients showed different genotypes in tumor and normal tissue. Conclusion: Prothrombin 3' end gene variants may play a role in colorectal cancer.
PB  - Int Inst Anticancer Research, Athens
T2  - Anticancer Research
T1  - Prothrombin 3'end Gene Variants in Patients With Sporadic Colon Adenocarcinoma
EP  - 6071
IS  - 11
SP  - 6067
VL  - 39
DO  - 10.21873/anticanres.13814
ER  - 

@article{
author = "Cumbo, Marija and Tomić, Branko and Dunjić Manevski, Sofija and Jovanović, Tamara and Gvozdenov, Maja and Pruner, Iva and Aralica, Gorana and Kapitanović, Sanja and Cacev, Tamara and Đorđević, Valentina",
year = "2019",
abstract = "Background/ Aim: Thrombin plays significant roles in various types of cancer. However, the expression levels of prothrombin, the thrombin precursor, in cancer remain unclear. Variants of the 3'end of the prothrombin gene lead to increased prothrombin expression. This study aimed to analyze prothrombin 3'end gene variants in colon tumor and adjacent normal tissue samples. Materials and Methods: The study group consisted of 93 patients suffering from colon adenocarcinoma. The 3'end of the prothrombin gene was analyzed by DNA sequencing. Results: Three variants, all previously associated with increased prothrombin expression were detected. Frequency of the FII 19911G allele was 46.77% and 47.85% in tumor and normal tissue, respectively. For the FII 20210A allele, the detected frequencies were 2.15% and 1.61%, respectively. The frequency of the FII c.1824T allele was 0.54% in both tissues. Four patients showed different genotypes in tumor and normal tissue. Conclusion: Prothrombin 3' end gene variants may play a role in colorectal cancer.",
publisher = "Int Inst Anticancer Research, Athens",
journal = "Anticancer Research",
title = "Prothrombin 3'end Gene Variants in Patients With Sporadic Colon Adenocarcinoma",
pages = "6071-6067",
number = "11",
volume = "39",
doi = "10.21873/anticanres.13814"
}

Cumbo, M., Tomić, B., Dunjić Manevski, S., Jovanović, T., Gvozdenov, M., Pruner, I., Aralica, G., Kapitanović, S., Cacev, T.,& Đorđević, V.. (2019). Prothrombin 3'end Gene Variants in Patients With Sporadic Colon Adenocarcinoma. in Anticancer Research
Int Inst Anticancer Research, Athens., 39(11), 6067-6071.
https://doi.org/10.21873/anticanres.13814

Cumbo M, Tomić B, Dunjić Manevski S, Jovanović T, Gvozdenov M, Pruner I, Aralica G, Kapitanović S, Cacev T, Đorđević V. Prothrombin 3'end Gene Variants in Patients With Sporadic Colon Adenocarcinoma. in Anticancer Research. 2019;39(11):6067-6071.
doi:10.21873/anticanres.13814 .

Cumbo, Marija, Tomić, Branko, Dunjić Manevski, Sofija, Jovanović, Tamara, Gvozdenov, Maja, Pruner, Iva, Aralica, Gorana, Kapitanović, Sanja, Cacev, Tamara, Đorđević, Valentina, "Prothrombin 3'end Gene Variants in Patients With Sporadic Colon Adenocarcinoma" in Anticancer Research, 39, no. 11 (2019):6067-6071,
https://doi.org/10.21873/anticanres.13814 . .

TY  - JOUR
AU  - Kovač, Mirjana
AU  - Kovac, Zeljko
AU  - Tomasević, Zorica
AU  - Tomić, Branko
AU  - Gvozdenov, Maja
AU  - Radojković, Dragica
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1250
PB  - Wiley, Hoboken
T2  - Breast Journal
T1  - Breast cancer and recurrent thrombosis - Results from prospective single center study
EP  - 785
IS  - 4
SP  - 783
VL  - 25
DO  - 10.1111/tbj.13326
ER  - 

@article{
author = "Kovač, Mirjana and Kovac, Zeljko and Tomasević, Zorica and Tomić, Branko and Gvozdenov, Maja and Radojković, Dragica",
year = "2019",
publisher = "Wiley, Hoboken",
journal = "Breast Journal",
title = "Breast cancer and recurrent thrombosis - Results from prospective single center study",
pages = "785-783",
number = "4",
volume = "25",
doi = "10.1111/tbj.13326"
}

Kovač, M., Kovac, Z., Tomasević, Z., Tomić, B., Gvozdenov, M.,& Radojković, D.. (2019). Breast cancer and recurrent thrombosis - Results from prospective single center study. in Breast Journal
Wiley, Hoboken., 25(4), 783-785.
https://doi.org/10.1111/tbj.13326

Kovač M, Kovac Z, Tomasević Z, Tomić B, Gvozdenov M, Radojković D. Breast cancer and recurrent thrombosis - Results from prospective single center study. in Breast Journal. 2019;25(4):783-785.
doi:10.1111/tbj.13326 .

Kovač, Mirjana, Kovac, Zeljko, Tomasević, Zorica, Tomić, Branko, Gvozdenov, Maja, Radojković, Dragica, "Breast cancer and recurrent thrombosis - Results from prospective single center study" in Breast Journal, 25, no. 4 (2019):783-785,
https://doi.org/10.1111/tbj.13326 . .

TY  - JOUR
AU  - Dunjić Manevski, Sofija
AU  - Cumbo, Marija
AU  - Gvozdenov, Maja
AU  - Tomić, Branko
AU  - Pruner, Iva
AU  - Radojković, Dragica
AU  - Đorđević, Valentina
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1244
AB  - The link between thrombotic disorders and cancer has been known for over 150 years, although the precise mechanism of this relationship has not yet been resolved. Current data show that thrombin has a significant role in cancer metabolism, invasiveness, adhesion and survival. However, data regarding the expression of the thrombin precursor prothrombin in various cancer cell lines are scarce. Therefore, it was our objective to determine whether common cancer-derived cell lines (Caco-2, MCF-7, SK-BR-3, U-87 and U-251) express prothrombin. The prothrombin RNA expression level was assessed by qPCR, and the presence of prothrombin was analyzed by Western blot analysis. Our results show that Caco-2 cells originating from colorectal adenocarcinoma express prothrombin, whereas other analyzed cell lines do not. Our results provide a background for further research into the role of (pro) thrombin in cancer etiopathology.
PB  - Srpsko biološko društvo, Beograd, i dr.
T2  - Archives of Biological Sciences
T1  - Prothrombin expression in cancer-derived cell lines
EP  - 54
IS  - 1
SP  - 49
VL  - 71
DO  - 10.2298/ABS180829046D
ER  - 

@article{
author = "Dunjić Manevski, Sofija and Cumbo, Marija and Gvozdenov, Maja and Tomić, Branko and Pruner, Iva and Radojković, Dragica and Đorđević, Valentina",
year = "2019",
abstract = "The link between thrombotic disorders and cancer has been known for over 150 years, although the precise mechanism of this relationship has not yet been resolved. Current data show that thrombin has a significant role in cancer metabolism, invasiveness, adhesion and survival. However, data regarding the expression of the thrombin precursor prothrombin in various cancer cell lines are scarce. Therefore, it was our objective to determine whether common cancer-derived cell lines (Caco-2, MCF-7, SK-BR-3, U-87 and U-251) express prothrombin. The prothrombin RNA expression level was assessed by qPCR, and the presence of prothrombin was analyzed by Western blot analysis. Our results show that Caco-2 cells originating from colorectal adenocarcinoma express prothrombin, whereas other analyzed cell lines do not. Our results provide a background for further research into the role of (pro) thrombin in cancer etiopathology.",
publisher = "Srpsko biološko društvo, Beograd, i dr.",
journal = "Archives of Biological Sciences",
title = "Prothrombin expression in cancer-derived cell lines",
pages = "54-49",
number = "1",
volume = "71",
doi = "10.2298/ABS180829046D"
}

Dunjić Manevski, S., Cumbo, M., Gvozdenov, M., Tomić, B., Pruner, I., Radojković, D.,& Đorđević, V.. (2019). Prothrombin expression in cancer-derived cell lines. in Archives of Biological Sciences
Srpsko biološko društvo, Beograd, i dr.., 71(1), 49-54.
https://doi.org/10.2298/ABS180829046D

Dunjić Manevski S, Cumbo M, Gvozdenov M, Tomić B, Pruner I, Radojković D, Đorđević V. Prothrombin expression in cancer-derived cell lines. in Archives of Biological Sciences. 2019;71(1):49-54.
doi:10.2298/ABS180829046D .

Dunjić Manevski, Sofija, Cumbo, Marija, Gvozdenov, Maja, Tomić, Branko, Pruner, Iva, Radojković, Dragica, Đorđević, Valentina, "Prothrombin expression in cancer-derived cell lines" in Archives of Biological Sciences, 71, no. 1 (2019):49-54,
https://doi.org/10.2298/ABS180829046D . .

TY  - JOUR
AU  - Pruner, Iva
AU  - Tomić, Branko
AU  - Dragojević, Marija
AU  - Gvozdenov, Maja
AU  - Kovač, Mirjana
AU  - Radojković, Dragica
AU  - Đorđević, Valentina
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1209
AB  - Breast cancer is the leading cause of cancer-related death among women. An increased burden of thrombotic events among breast cancer patients, leading to higher mortality and morbidity rates, is well established. There are a number of genetic risk factors associated with thrombosis, but their contribution to thrombotic tendencies in patients with cancer is not completely elucidated. We aimed to investigate possible role of FV Leiden, FII G20210A, MTHFR C677T and PAI-1 4G/5G gene variants in etiopathology of breast cancer and accompanying thrombosis in cohort of Serbian patients. Our study included 316 subject divided in three groups: breast cancer patients with (97) or without (99) accompanying thrombosis and healthy control group (120). According to our results, the prevalence for all four prothrombotic gene variants were similar in cancer patients with and without thrombosis and no statistically significant difference was observed between these groups. We detected lower frequency of MTHFR 677TT genotype in breast cancer patients when compared to control group (P=0.014; OR=0.145 (95%CI 0.031-0.679)), indicated that MTHFR C677T homozygosity could play a protective role in breast cancer susceptibility. Our study noted the lack of association between common prothrombotic gene variants and increased prothrombotic risk in Serbian breast cancer patients. Also, our results point out possible role of MTHFR 677TT genotype in etiology of breast cancer, but further studies on larger cohort of patients are needed.
PB  - Društvo genetičara Srbije, Beograd
T2  - Genetika-Belgrade
T1  - Inherited thrombophilic risk factors in Serbian breast cancer patients
EP  - 472
IS  - 2
SP  - 463
VL  - 51
DO  - 10.2298/GENSR1902463P
ER  - 

@article{
author = "Pruner, Iva and Tomić, Branko and Dragojević, Marija and Gvozdenov, Maja and Kovač, Mirjana and Radojković, Dragica and Đorđević, Valentina",
year = "2019",
abstract = "Breast cancer is the leading cause of cancer-related death among women. An increased burden of thrombotic events among breast cancer patients, leading to higher mortality and morbidity rates, is well established. There are a number of genetic risk factors associated with thrombosis, but their contribution to thrombotic tendencies in patients with cancer is not completely elucidated. We aimed to investigate possible role of FV Leiden, FII G20210A, MTHFR C677T and PAI-1 4G/5G gene variants in etiopathology of breast cancer and accompanying thrombosis in cohort of Serbian patients. Our study included 316 subject divided in three groups: breast cancer patients with (97) or without (99) accompanying thrombosis and healthy control group (120). According to our results, the prevalence for all four prothrombotic gene variants were similar in cancer patients with and without thrombosis and no statistically significant difference was observed between these groups. We detected lower frequency of MTHFR 677TT genotype in breast cancer patients when compared to control group (P=0.014; OR=0.145 (95%CI 0.031-0.679)), indicated that MTHFR C677T homozygosity could play a protective role in breast cancer susceptibility. Our study noted the lack of association between common prothrombotic gene variants and increased prothrombotic risk in Serbian breast cancer patients. Also, our results point out possible role of MTHFR 677TT genotype in etiology of breast cancer, but further studies on larger cohort of patients are needed.",
publisher = "Društvo genetičara Srbije, Beograd",
journal = "Genetika-Belgrade",
title = "Inherited thrombophilic risk factors in Serbian breast cancer patients",
pages = "472-463",
number = "2",
volume = "51",
doi = "10.2298/GENSR1902463P"
}

Pruner, I., Tomić, B., Dragojević, M., Gvozdenov, M., Kovač, M., Radojković, D.,& Đorđević, V.. (2019). Inherited thrombophilic risk factors in Serbian breast cancer patients. in Genetika-Belgrade
Društvo genetičara Srbije, Beograd., 51(2), 463-472.
https://doi.org/10.2298/GENSR1902463P

Pruner I, Tomić B, Dragojević M, Gvozdenov M, Kovač M, Radojković D, Đorđević V. Inherited thrombophilic risk factors in Serbian breast cancer patients. in Genetika-Belgrade. 2019;51(2):463-472.
doi:10.2298/GENSR1902463P .

Pruner, Iva, Tomić, Branko, Dragojević, Marija, Gvozdenov, Maja, Kovač, Mirjana, Radojković, Dragica, Đorđević, Valentina, "Inherited thrombophilic risk factors in Serbian breast cancer patients" in Genetika-Belgrade, 51, no. 2 (2019):463-472,
https://doi.org/10.2298/GENSR1902463P . .

TY  - JOUR
AU  - Kovač, Mirjana
AU  - Mitić, Gorana
AU  - Miković, Zeljko
AU  - Mandić, Vesna
AU  - Miljić, Predrag
AU  - Mitrović, Mirjana
AU  - Tomić, Branko
AU  - Bereczky, Zsuzsanna
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1287
AB  - Background: Inherited antithrombin (AT) deficiency is a rare autosomal dominant disorder, caused by mutations in the SERPINC1 gene. The most common clinical presentation in AT deficient patients includes venous thrombosis and pulmonary embolism, while the association of AT deficiency and its effect on the development of pregnancy complications has been less studied. The aim of our research was to evaluate the effect of AT deficiency types, determined by genotyping, on pregnancy outcomes. Methods: A retrospective cohort study included 28 women with AT deficiency, and their 64 pregnancies were analyzed. Results: With regard to live birth rate, a significant difference was observed among women who were carriers of different SERPINC1 mutations, as the rate varied from 100% in cases of type I to the extremely low rate of 8% for women with type II HBS (AT Budapest 3) in the homozygous variant, P=0.0005. All pregnancies from the type I group, even untreated ones, resulted in live births. In women with AT Budapest 3 in homozygous variant the overall live birth rate increased to 28.5% in the treated pregnancies. In this group the highest incidence of fetal death was observed of 62%; repeated fetal losses in 30%; fetal growth restriction in 22% and placental abruption in 7% of all pregnancies. Conclusion: Our study results indicate a difference between type I and type II AT deficiency. The risk of pregnancy related VTE was equally present in both groups, except for AT Budapest 3 in the heterozygous variant, while adverse pregnancy outcomes were strictly related to type II, especially AT Budapest 3 in the homozygous variant.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Thrombosis Research
T1  - The influence of specific mutations in the AT gene (SERPINC1) on the type of pregnancy related complications
EP  - 19
SP  - 12
VL  - 173
DO  - 10.1016/j.thromres.2018.11.006
ER  - 

@article{
author = "Kovač, Mirjana and Mitić, Gorana and Miković, Zeljko and Mandić, Vesna and Miljić, Predrag and Mitrović, Mirjana and Tomić, Branko and Bereczky, Zsuzsanna",
year = "2019",
abstract = "Background: Inherited antithrombin (AT) deficiency is a rare autosomal dominant disorder, caused by mutations in the SERPINC1 gene. The most common clinical presentation in AT deficient patients includes venous thrombosis and pulmonary embolism, while the association of AT deficiency and its effect on the development of pregnancy complications has been less studied. The aim of our research was to evaluate the effect of AT deficiency types, determined by genotyping, on pregnancy outcomes. Methods: A retrospective cohort study included 28 women with AT deficiency, and their 64 pregnancies were analyzed. Results: With regard to live birth rate, a significant difference was observed among women who were carriers of different SERPINC1 mutations, as the rate varied from 100% in cases of type I to the extremely low rate of 8% for women with type II HBS (AT Budapest 3) in the homozygous variant, P=0.0005. All pregnancies from the type I group, even untreated ones, resulted in live births. In women with AT Budapest 3 in homozygous variant the overall live birth rate increased to 28.5% in the treated pregnancies. In this group the highest incidence of fetal death was observed of 62%; repeated fetal losses in 30%; fetal growth restriction in 22% and placental abruption in 7% of all pregnancies. Conclusion: Our study results indicate a difference between type I and type II AT deficiency. The risk of pregnancy related VTE was equally present in both groups, except for AT Budapest 3 in the heterozygous variant, while adverse pregnancy outcomes were strictly related to type II, especially AT Budapest 3 in the homozygous variant.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Thrombosis Research",
title = "The influence of specific mutations in the AT gene (SERPINC1) on the type of pregnancy related complications",
pages = "19-12",
volume = "173",
doi = "10.1016/j.thromres.2018.11.006"
}

Kovač, M., Mitić, G., Miković, Z., Mandić, V., Miljić, P., Mitrović, M., Tomić, B.,& Bereczky, Z.. (2019). The influence of specific mutations in the AT gene (SERPINC1) on the type of pregnancy related complications. in Thrombosis Research
Pergamon-Elsevier Science Ltd, Oxford., 173, 12-19.
https://doi.org/10.1016/j.thromres.2018.11.006

Kovač M, Mitić G, Miković Z, Mandić V, Miljić P, Mitrović M, Tomić B, Bereczky Z. The influence of specific mutations in the AT gene (SERPINC1) on the type of pregnancy related complications. in Thrombosis Research. 2019;173:12-19.
doi:10.1016/j.thromres.2018.11.006 .

Kovač, Mirjana, Mitić, Gorana, Miković, Zeljko, Mandić, Vesna, Miljić, Predrag, Mitrović, Mirjana, Tomić, Branko, Bereczky, Zsuzsanna, "The influence of specific mutations in the AT gene (SERPINC1) on the type of pregnancy related complications" in Thrombosis Research, 173 (2019):12-19,
https://doi.org/10.1016/j.thromres.2018.11.006 . .

TY  - JOUR
AU  - Kovač, Mirjana
AU  - Mitić, Gorana
AU  - Đilas, Iva
AU  - Kuzmanović, Milos
AU  - Serbić, Olivera
AU  - Leković, Danijela
AU  - Tomić, Branko
AU  - Bereczky, Zsuzsanna
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1208
AB  - Inherited antithrombin (AT) deficiency is a rare autosomal dominant disorder, caused by mutations in the AT gene (SERPINC1). Considering that the genotype phenotype relationship in AT deficiency patients remains unclear, especially in pediatric patients, the aim of our study was to evaluate genotype phenotype correlation in a Serbian pediatric population. A retrospective cohort study included 19 children younger than 18 years, from 15 Serbian families, with newly diagnosed AT deficiency. In 21% of the recruited families, mutations affecting exon 4, 5, and 6 of the SERPINC1 gene that causes type I AT deficiency were detected. In the remaining families, the mutation in exon 2 causing type II HBS (AT Budapest 3) was found. Thrombosis events were observed in 1 (33%) of those with type I, 11 (85%) of those with AT Budapest 3 in the homozygous respectively, and 1(33%) in the heterozygous form. Recurrent thrombosis was observed only in AT Budapest 3 in the homozygous form, in 27% during initial treatment of the first thrombotic event. Abdominal venous thrombosis and arterial ischemic stroke, observed in almost half of the children from the group with AT Budapest 3 in the homozygous form, were unprovoked in all cases. Conclusion: Type II HBS (AT Budapest 3) in the homozygous form is a strong risk factor for arterial and venous thrombosis in pediatric patients.What is Known:center dot Inherited AT deficiency is a rare autosomal dominant disorder, caused by mutations in the SERPINC1gene.center dot The genotype phenotype correlation in AT deficiency patients remains unclear, especially in pediatric patients.What is New:center dot The genetic results for our paediatric population predominantly showed the presence of a single specific mutation in exon 2, that causes type II HBS deficiency (AT Budapest 3).center dot In this group thrombosis mostly occurred as unprovoked, in almost half of them as abdominal thrombosis or stroke with high incidence of recurrent thrombosis, in 27% during initial treatment.
PB  - Springer, New York
T2  - European Journal of Pediatrics
T1  - Genotype phenotype correlation in a pediatric population with antithrombin deficiency
EP  - 1478
IS  - 10
SP  - 1471
VL  - 178
DO  - 10.1007/s00431-019-03433-5
ER  - 

@article{
author = "Kovač, Mirjana and Mitić, Gorana and Đilas, Iva and Kuzmanović, Milos and Serbić, Olivera and Leković, Danijela and Tomić, Branko and Bereczky, Zsuzsanna",
year = "2019",
abstract = "Inherited antithrombin (AT) deficiency is a rare autosomal dominant disorder, caused by mutations in the AT gene (SERPINC1). Considering that the genotype phenotype relationship in AT deficiency patients remains unclear, especially in pediatric patients, the aim of our study was to evaluate genotype phenotype correlation in a Serbian pediatric population. A retrospective cohort study included 19 children younger than 18 years, from 15 Serbian families, with newly diagnosed AT deficiency. In 21% of the recruited families, mutations affecting exon 4, 5, and 6 of the SERPINC1 gene that causes type I AT deficiency were detected. In the remaining families, the mutation in exon 2 causing type II HBS (AT Budapest 3) was found. Thrombosis events were observed in 1 (33%) of those with type I, 11 (85%) of those with AT Budapest 3 in the homozygous respectively, and 1(33%) in the heterozygous form. Recurrent thrombosis was observed only in AT Budapest 3 in the homozygous form, in 27% during initial treatment of the first thrombotic event. Abdominal venous thrombosis and arterial ischemic stroke, observed in almost half of the children from the group with AT Budapest 3 in the homozygous form, were unprovoked in all cases. Conclusion: Type II HBS (AT Budapest 3) in the homozygous form is a strong risk factor for arterial and venous thrombosis in pediatric patients.What is Known:center dot Inherited AT deficiency is a rare autosomal dominant disorder, caused by mutations in the SERPINC1gene.center dot The genotype phenotype correlation in AT deficiency patients remains unclear, especially in pediatric patients.What is New:center dot The genetic results for our paediatric population predominantly showed the presence of a single specific mutation in exon 2, that causes type II HBS deficiency (AT Budapest 3).center dot In this group thrombosis mostly occurred as unprovoked, in almost half of them as abdominal thrombosis or stroke with high incidence of recurrent thrombosis, in 27% during initial treatment.",
publisher = "Springer, New York",
journal = "European Journal of Pediatrics",
title = "Genotype phenotype correlation in a pediatric population with antithrombin deficiency",
pages = "1478-1471",
number = "10",
volume = "178",
doi = "10.1007/s00431-019-03433-5"
}

Kovač, M., Mitić, G., Đilas, I., Kuzmanović, M., Serbić, O., Leković, D., Tomić, B.,& Bereczky, Z.. (2019). Genotype phenotype correlation in a pediatric population with antithrombin deficiency. in European Journal of Pediatrics
Springer, New York., 178(10), 1471-1478.
https://doi.org/10.1007/s00431-019-03433-5

Kovač M, Mitić G, Đilas I, Kuzmanović M, Serbić O, Leković D, Tomić B, Bereczky Z. Genotype phenotype correlation in a pediatric population with antithrombin deficiency. in European Journal of Pediatrics. 2019;178(10):1471-1478.
doi:10.1007/s00431-019-03433-5 .

Kovač, Mirjana, Mitić, Gorana, Đilas, Iva, Kuzmanović, Milos, Serbić, Olivera, Leković, Danijela, Tomić, Branko, Bereczky, Zsuzsanna, "Genotype phenotype correlation in a pediatric population with antithrombin deficiency" in European Journal of Pediatrics, 178, no. 10 (2019):1471-1478,
https://doi.org/10.1007/s00431-019-03433-5 . .

TY  - JOUR
AU  - Vucković, Biljana A.
AU  - Đerić, Mirjana J.
AU  - Tomić, Branko
AU  - Đorđević, Valentina
AU  - Bajkin, Branislav V.
AU  - Mitić, Gorana P.
PY  - 2018
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1177
AB  - Objective of our study is to determine whether decreased fibrinolytic activity or plasminogen activator inhibitor (PAI)-1 4G/5G polymorphism influence the risk of venous thrombosis. Our case-control study included 100 patients with venous thrombosis, and 100 random controls. When patients were compared with random controls, unconditional logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs). Decreased fibrinolytic activity yielded a 2.7-fold increase in risk for venous thrombosis than physiological fibrinolytic activity (OR 2.70; 95% CI 1.22-5.98), when comparing patients with random controls. Adjustment for several putative confounders did not change the estimate (OR 3.02; 95% CI 1.26-7.22). Analysis of venous thrombotic risk influenced by PAI-1 genotype, showed no influence of PAI-1 4G/5G gene variant in comparison with 5G/5G genotype (OR 0.57 95% CI; 0.27-1.20). Decreased fibrinolytic activity increased, whereas PAI-1 4G/5G polymorphism did not influence venous thrombosis risk in this study.
PB  - Lippincott Williams & Wilkins, Philadelphia
T2  - Blood Coagulation & Fibrinolysis
T1  - Influence of decreased fibrinolytic activity and plasminogen activator inhibitor-1 4G/5G polymorphism on the risk of venous thrombosis
EP  - 24
IS  - 1
SP  - 19
VL  - 29
DO  - 10.1097/MBC.0000000000000656
ER  - 

@article{
author = "Vucković, Biljana A. and Đerić, Mirjana J. and Tomić, Branko and Đorđević, Valentina and Bajkin, Branislav V. and Mitić, Gorana P.",
year = "2018",
abstract = "Objective of our study is to determine whether decreased fibrinolytic activity or plasminogen activator inhibitor (PAI)-1 4G/5G polymorphism influence the risk of venous thrombosis. Our case-control study included 100 patients with venous thrombosis, and 100 random controls. When patients were compared with random controls, unconditional logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs). Decreased fibrinolytic activity yielded a 2.7-fold increase in risk for venous thrombosis than physiological fibrinolytic activity (OR 2.70; 95% CI 1.22-5.98), when comparing patients with random controls. Adjustment for several putative confounders did not change the estimate (OR 3.02; 95% CI 1.26-7.22). Analysis of venous thrombotic risk influenced by PAI-1 genotype, showed no influence of PAI-1 4G/5G gene variant in comparison with 5G/5G genotype (OR 0.57 95% CI; 0.27-1.20). Decreased fibrinolytic activity increased, whereas PAI-1 4G/5G polymorphism did not influence venous thrombosis risk in this study.",
publisher = "Lippincott Williams & Wilkins, Philadelphia",
journal = "Blood Coagulation & Fibrinolysis",
title = "Influence of decreased fibrinolytic activity and plasminogen activator inhibitor-1 4G/5G polymorphism on the risk of venous thrombosis",
pages = "24-19",
number = "1",
volume = "29",
doi = "10.1097/MBC.0000000000000656"
}

Vucković, B. A., Đerić, M. J., Tomić, B., Đorđević, V., Bajkin, B. V.,& Mitić, G. P.. (2018). Influence of decreased fibrinolytic activity and plasminogen activator inhibitor-1 4G/5G polymorphism on the risk of venous thrombosis. in Blood Coagulation & Fibrinolysis
Lippincott Williams & Wilkins, Philadelphia., 29(1), 19-24.
https://doi.org/10.1097/MBC.0000000000000656

Vucković BA, Đerić MJ, Tomić B, Đorđević V, Bajkin BV, Mitić GP. Influence of decreased fibrinolytic activity and plasminogen activator inhibitor-1 4G/5G polymorphism on the risk of venous thrombosis. in Blood Coagulation & Fibrinolysis. 2018;29(1):19-24.
doi:10.1097/MBC.0000000000000656 .

Vucković, Biljana A., Đerić, Mirjana J., Tomić, Branko, Đorđević, Valentina, Bajkin, Branislav V., Mitić, Gorana P., "Influence of decreased fibrinolytic activity and plasminogen activator inhibitor-1 4G/5G polymorphism on the risk of venous thrombosis" in Blood Coagulation & Fibrinolysis, 29, no. 1 (2018):19-24,
https://doi.org/10.1097/MBC.0000000000000656 . .