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  - Pruner, Iva
AU  - Nikolić, Aleksandra
PY  - 2023
UR  - https://belbi.bg.ac.rs/
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2034
AB  - Colorectal cancer (CRC) is one of the most commonly diagnosed cancers worldwide. Lack
of specific CRC symptoms is a challenge for clinicians, as the symptoms overlap with other
non-cancerous diseases, leading to 20-25% of newly diagnosed CRC patients already
having liver metastasis. Thus, discovering reliable early-disease biomarkers is of high
importance. Non-coding RNAs (ncRNAs) have been demonstrated to be involved in CRC
development and progression. Long non-coding RNAs (lncRNAs) can interact with RNA,
DNA and proteins, forming complexes that are involved in regulation of gene expression
via multiple mechanisms, affecting every stage of colon carcinogenesis and making them
top candidates for novel biomarker discovery.
The aim of our study was to conduct data mining of Gene Expression Omnibus (GEO)
database by using “colon cancer” and “ncRNA” keywords, and identify differentially
expressed lnRNAs present in different GEO datasets.
GEO database which collects submitted high-throughput gene expression data was queried
for all datasets that studied colon cancer and ncRNA. Over 60 datasets were manually
inspected in order to identify those where analysis of colon and normal tissue originating
from the same patient was done. Each dataset was analyzed by GEO2R software to
discover differentially expressed lncRNAs. LncRNAs were considered significant if they
appeared in more than one GEO dataset. Parts of lncRNAs sequences available in GEO2R
analysis results were run through BLAST in order to identify full length lncRNAs.
Five GEO datasets matched our criteria. We discovered 12 sequences that appeared in
more than one dataset and we identified them through BLAST analysis. Six sequences
originated from lncRNAs (RYR3 divergent transcript, long intergenic non-protein coding
RNA 595, TOX divergent transcript, FLVCR2 antisense RNA 1, LHRI_LNC744.1 lncRNA
gene, and ELFN1 antisense RNA 1), while six sequences represented partial sequences
of various mRNAs. Four lncRNAs were down-regulated in colon cancer; one was upregulated,
while one showed different expression patterns in different GEO datasets.
In this study, we have identified six lncRNAs that have potential significance for colorectal
cancer etiology and will be a subject of further in silico and in vitro study.
PB  - Belgrade : Institute of molecular genetics and genetic engineering
C3  - 4th Belgrade Bioinformatics Conference
T1  - Data mining for long-non coding RNAs deregulated in colon cancer through analysis of Gene Expression Omnibus database
EP  - 89
SP  - 89
VL  - 4
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2034
ER  - 

@conference{
author = "Pruner, Iva and Nikolić, Aleksandra",
year = "2023",
abstract = "Colorectal cancer (CRC) is one of the most commonly diagnosed cancers worldwide. Lack
of specific CRC symptoms is a challenge for clinicians, as the symptoms overlap with other
non-cancerous diseases, leading to 20-25% of newly diagnosed CRC patients already
having liver metastasis. Thus, discovering reliable early-disease biomarkers is of high
importance. Non-coding RNAs (ncRNAs) have been demonstrated to be involved in CRC
development and progression. Long non-coding RNAs (lncRNAs) can interact with RNA,
DNA and proteins, forming complexes that are involved in regulation of gene expression
via multiple mechanisms, affecting every stage of colon carcinogenesis and making them
top candidates for novel biomarker discovery.
The aim of our study was to conduct data mining of Gene Expression Omnibus (GEO)
database by using “colon cancer” and “ncRNA” keywords, and identify differentially
expressed lnRNAs present in different GEO datasets.
GEO database which collects submitted high-throughput gene expression data was queried
for all datasets that studied colon cancer and ncRNA. Over 60 datasets were manually
inspected in order to identify those where analysis of colon and normal tissue originating
from the same patient was done. Each dataset was analyzed by GEO2R software to
discover differentially expressed lncRNAs. LncRNAs were considered significant if they
appeared in more than one GEO dataset. Parts of lncRNAs sequences available in GEO2R
analysis results were run through BLAST in order to identify full length lncRNAs.
Five GEO datasets matched our criteria. We discovered 12 sequences that appeared in
more than one dataset and we identified them through BLAST analysis. Six sequences
originated from lncRNAs (RYR3 divergent transcript, long intergenic non-protein coding
RNA 595, TOX divergent transcript, FLVCR2 antisense RNA 1, LHRI_LNC744.1 lncRNA
gene, and ELFN1 antisense RNA 1), while six sequences represented partial sequences
of various mRNAs. Four lncRNAs were down-regulated in colon cancer; one was upregulated,
while one showed different expression patterns in different GEO datasets.
In this study, we have identified six lncRNAs that have potential significance for colorectal
cancer etiology and will be a subject of further in silico and in vitro study.",
publisher = "Belgrade : Institute of molecular genetics and genetic engineering",
journal = "4th Belgrade Bioinformatics Conference",
title = "Data mining for long-non coding RNAs deregulated in colon cancer through analysis of Gene Expression Omnibus database",
pages = "89-89",
volume = "4",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2034"
}

Pruner, I.,& Nikolić, A.. (2023). Data mining for long-non coding RNAs deregulated in colon cancer through analysis of Gene Expression Omnibus database. in 4th Belgrade Bioinformatics Conference
Belgrade : Institute of molecular genetics and genetic engineering., 4, 89-89.
https://hdl.handle.net/21.15107/rcub_imagine_2034

Pruner I, Nikolić A. Data mining for long-non coding RNAs deregulated in colon cancer through analysis of Gene Expression Omnibus database. in 4th Belgrade Bioinformatics Conference. 2023;4:89-89.
https://hdl.handle.net/21.15107/rcub_imagine_2034 .

Pruner, Iva, Nikolić, Aleksandra, "Data mining for long-non coding RNAs deregulated in colon cancer through analysis of Gene Expression Omnibus database" in 4th Belgrade Bioinformatics Conference, 4 (2023):89-89,
https://hdl.handle.net/21.15107/rcub_imagine_2034 .

TY  - JOUR
AU  - Colić, Jelena
AU  - Pruner, Iva
AU  - Damjanov, Nemanja
AU  - Pekmezović, Tatjana
AU  - Sefik-Bukilica, Mirjana
AU  - Antović, Aleksandra
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1534
AB  - J Rheumatol 2022; doi: 10.3899/jrheum.210931

In the Methods section, under the subheading “Follow-up and study outcome,” the last sentence should be as follows: “All new DUs were recorded by contacting all 39 patients once every 1–3 months during follow-up.” The error does not affect the results or conclusions of the study.

This correction only applies to the April 1 First Release. The correct text appears in the print and online issues.
PB  - J Rheumatol Publ Co, Toronto
T2  - Journal of Rheumatology
T1  - Impaired Fibrinolysis Is Linked With Digital Vasculopathy and Onset of New Digital Ulcers in Systemic Sclerosis (vol 49, pg 598, 2022)
EP  - 440
IS  - 5
SP  - 440
VL  - 49
DO  - 10.3899/jrheum.210931.C1
ER  - 

@article{
author = "Colić, Jelena and Pruner, Iva and Damjanov, Nemanja and Pekmezović, Tatjana and Sefik-Bukilica, Mirjana and Antović, Aleksandra",
year = "2022",
abstract = "J Rheumatol 2022; doi: 10.3899/jrheum.210931

In the Methods section, under the subheading “Follow-up and study outcome,” the last sentence should be as follows: “All new DUs were recorded by contacting all 39 patients once every 1–3 months during follow-up.” The error does not affect the results or conclusions of the study.

This correction only applies to the April 1 First Release. The correct text appears in the print and online issues.",
publisher = "J Rheumatol Publ Co, Toronto",
journal = "Journal of Rheumatology",
title = "Impaired Fibrinolysis Is Linked With Digital Vasculopathy and Onset of New Digital Ulcers in Systemic Sclerosis (vol 49, pg 598, 2022)",
pages = "440-440",
number = "5",
volume = "49",
doi = "10.3899/jrheum.210931.C1"
}

Colić, J., Pruner, I., Damjanov, N., Pekmezović, T., Sefik-Bukilica, M.,& Antović, A.. (2022). Impaired Fibrinolysis Is Linked With Digital Vasculopathy and Onset of New Digital Ulcers in Systemic Sclerosis (vol 49, pg 598, 2022). in Journal of Rheumatology
J Rheumatol Publ Co, Toronto., 49(5), 440-440.
https://doi.org/10.3899/jrheum.210931.C1

Colić J, Pruner I, Damjanov N, Pekmezović T, Sefik-Bukilica M, Antović A. Impaired Fibrinolysis Is Linked With Digital Vasculopathy and Onset of New Digital Ulcers in Systemic Sclerosis (vol 49, pg 598, 2022). in Journal of Rheumatology. 2022;49(5):440-440.
doi:10.3899/jrheum.210931.C1 .

Colić, Jelena, Pruner, Iva, Damjanov, Nemanja, Pekmezović, Tatjana, Sefik-Bukilica, Mirjana, Antović, Aleksandra, "Impaired Fibrinolysis Is Linked With Digital Vasculopathy and Onset of New Digital Ulcers in Systemic Sclerosis (vol 49, pg 598, 2022)" in Journal of Rheumatology, 49, no. 5 (2022):440-440,
https://doi.org/10.3899/jrheum.210931.C1 . .

TY  - JOUR
AU  - Colić, Jelena
AU  - Pruner, Iva
AU  - Damjanov, Nemanja
AU  - Pekmezović, Tatjana
AU  - Sefik-Bukilica, Mirjana
AU  - Antović, Aleksandra
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1536
AB  - Objective. To assess thrombin generation, fibrin formation, and structure together with the fibrinolytic status in patients with systemic sclerosis (SSc) in relation to the occurrence of digital ulcers (DUs) during the course of disease. Methods. We studied variables of endothelial dysfunction, thrombin generation, overall hemostatic potential, and fibrin clot turbidity in plasma from 58 patients with SSc (39 with DU history and 19 DU-naive) and 46 matched healthy controls (HCs). Fibrin structure was visualized using scanning electron microscopy (SEM). Finally, 39 patients with a history of DUs were followed for 1.5 years and the predictive value of all investigated markers for new DU onset was explored. Results. Significantly enhanced endogenous thrombin potential (ETP) and prolonged clot lysis time (CLT) were found in patients with DUs compared to HCs. CLT was prolonged in patients with DUs compared to those without, showing good validity in identifying DUs with an area under the curve of 0.7 (95% CI 0.6-0.8). The levels of ETP and intercellular adhesion molecule 1 were independently associated with CLT. Over the follow-up period, 20 patients developed new DUs. CLT was prolonged (P  lt  0.001) in patients with new DU episodes, especially those with recurrent DUs. Regression analysis showed that the Raynaud phenomenon visual analog scale and CLT were predictors of new DUs (OR 1.1, 95% CI 1.0-1.1 and OR 1.2, 95% CI 1.1-1.3, respectively). SEM confirmed denser fibrin clots in patients with new DUs. Conclusion. Our results suggest that impaired fibrinolysis might have an emerging role in underlying digital vasculopathy and its progression in SSc.
PB  - Toronto : J Rheumatol Publ Co.
T2  - Journal of Rheumatology
T1  - Impaired Fibrinolysis Is Linked With Digital Vasculopathy and Onset of New Digital Ulcers in Systemic Sclerosis
EP  - 606
IS  - 6
SP  - 598
VL  - 49
DO  - 10.3899/jrheum.210931
ER  - 

@article{
author = "Colić, Jelena and Pruner, Iva and Damjanov, Nemanja and Pekmezović, Tatjana and Sefik-Bukilica, Mirjana and Antović, Aleksandra",
year = "2022",
abstract = "Objective. To assess thrombin generation, fibrin formation, and structure together with the fibrinolytic status in patients with systemic sclerosis (SSc) in relation to the occurrence of digital ulcers (DUs) during the course of disease. Methods. We studied variables of endothelial dysfunction, thrombin generation, overall hemostatic potential, and fibrin clot turbidity in plasma from 58 patients with SSc (39 with DU history and 19 DU-naive) and 46 matched healthy controls (HCs). Fibrin structure was visualized using scanning electron microscopy (SEM). Finally, 39 patients with a history of DUs were followed for 1.5 years and the predictive value of all investigated markers for new DU onset was explored. Results. Significantly enhanced endogenous thrombin potential (ETP) and prolonged clot lysis time (CLT) were found in patients with DUs compared to HCs. CLT was prolonged in patients with DUs compared to those without, showing good validity in identifying DUs with an area under the curve of 0.7 (95% CI 0.6-0.8). The levels of ETP and intercellular adhesion molecule 1 were independently associated with CLT. Over the follow-up period, 20 patients developed new DUs. CLT was prolonged (P  lt  0.001) in patients with new DU episodes, especially those with recurrent DUs. Regression analysis showed that the Raynaud phenomenon visual analog scale and CLT were predictors of new DUs (OR 1.1, 95% CI 1.0-1.1 and OR 1.2, 95% CI 1.1-1.3, respectively). SEM confirmed denser fibrin clots in patients with new DUs. Conclusion. Our results suggest that impaired fibrinolysis might have an emerging role in underlying digital vasculopathy and its progression in SSc.",
publisher = "Toronto : J Rheumatol Publ Co.",
journal = "Journal of Rheumatology",
title = "Impaired Fibrinolysis Is Linked With Digital Vasculopathy and Onset of New Digital Ulcers in Systemic Sclerosis",
pages = "606-598",
number = "6",
volume = "49",
doi = "10.3899/jrheum.210931"
}

Colić, J., Pruner, I., Damjanov, N., Pekmezović, T., Sefik-Bukilica, M.,& Antović, A.. (2022). Impaired Fibrinolysis Is Linked With Digital Vasculopathy and Onset of New Digital Ulcers in Systemic Sclerosis. in Journal of Rheumatology
Toronto : J Rheumatol Publ Co.., 49(6), 598-606.
https://doi.org/10.3899/jrheum.210931

Colić J, Pruner I, Damjanov N, Pekmezović T, Sefik-Bukilica M, Antović A. Impaired Fibrinolysis Is Linked With Digital Vasculopathy and Onset of New Digital Ulcers in Systemic Sclerosis. in Journal of Rheumatology. 2022;49(6):598-606.
doi:10.3899/jrheum.210931 .

Colić, Jelena, Pruner, Iva, Damjanov, Nemanja, Pekmezović, Tatjana, Sefik-Bukilica, Mirjana, Antović, Aleksandra, "Impaired Fibrinolysis Is Linked With Digital Vasculopathy and Onset of New Digital Ulcers in Systemic Sclerosis" in Journal of Rheumatology, 49, no. 6 (2022):598-606,
https://doi.org/10.3899/jrheum.210931 . .

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  - Stojanović, Aleksandra
AU  - Veselinović, Mirjana
AU  - Zong, Yanan
AU  - Jakovljević, Vladimir
AU  - Pruner, Iva
AU  - Antović, Aleksandra
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1454
AB  - This study sought to identify different subpopulations of extracellular vesicles (EVs) in plasma from female patients with established rheumatoid arthritis (RA) in relation to the activation of coagulation and fibrin formation in these patients. Forty women were included in the study, 20 patients and 20 age-matched healthy controls. The mean disease duration in patients was 13.0 (5.0-25.0) years, with medium to high disease activity despite ongoing treatment with low-dose prednisolone and methotrexate. There were no differences between the investigated groups regarding the presence of traditional cardiovascular risk factors. The concentration of phosphatidylserine-positive (PS+) EVs; platelet (CD42a(+)), leucocyte (CD45(+)), monocyte (CD14(+)), and endothelial (CD144(+))-derived EVs; and EVs-expressing tissue factor (CD142(+)), P-selectin (CD62P(+)), and E-selectin (CD62E(+)) were determined by flow cytometry analysis. Overall hemostasis potential (OHP) was assessed to follow the hemostatic disturbances, including the parameters for overall coagulation potential (OCP) and overall fibrinolytic potential (OFP). Fibrin clot turbidity was measured together with clot lysis time, and scanning electron microscopy was performed. Increased concentrations of PS+, CD42a(+), CD142(+), CD45(+), CD14(+), and CD62P(+) EVs were found in plasma from patients with RA compared to healthy controls, and the concentrations of PS+, CD42a(+), CD14(+), and CD62P(+) EVs were positively correlated with the inflammatory parameters in RA patients. Positive correlations were also found between the levels of PS+ and CD42a(+) EVs and OCP as well as between the levels of PS+, CD42a(+), and CD62P(+)EVs and OHP. The levels of PS+, CD42a(+), CD14(+), CD62P(+), and CD62E(+) EVs were negatively correlated with OFP. Elevated levels of circulating EVs of different cell origins were found in patients with established RA, in relation to the inflammatory burden and coagulation activation in the disease.
PB  - Frontiers Media Sa, Lausanne
T2  - Frontiers in Immunology
T1  - Increased Expression of Extracellular Vesicles Is Associated With the Procoagulant State in Patients With Established Rheumatoid Arthritis
VL  - 12
DO  - 10.3389/fimmu.2021.718845
ER  - 

@article{
author = "Stojanović, Aleksandra and Veselinović, Mirjana and Zong, Yanan and Jakovljević, Vladimir and Pruner, Iva and Antović, Aleksandra",
year = "2021",
abstract = "This study sought to identify different subpopulations of extracellular vesicles (EVs) in plasma from female patients with established rheumatoid arthritis (RA) in relation to the activation of coagulation and fibrin formation in these patients. Forty women were included in the study, 20 patients and 20 age-matched healthy controls. The mean disease duration in patients was 13.0 (5.0-25.0) years, with medium to high disease activity despite ongoing treatment with low-dose prednisolone and methotrexate. There were no differences between the investigated groups regarding the presence of traditional cardiovascular risk factors. The concentration of phosphatidylserine-positive (PS+) EVs; platelet (CD42a(+)), leucocyte (CD45(+)), monocyte (CD14(+)), and endothelial (CD144(+))-derived EVs; and EVs-expressing tissue factor (CD142(+)), P-selectin (CD62P(+)), and E-selectin (CD62E(+)) were determined by flow cytometry analysis. Overall hemostasis potential (OHP) was assessed to follow the hemostatic disturbances, including the parameters for overall coagulation potential (OCP) and overall fibrinolytic potential (OFP). Fibrin clot turbidity was measured together with clot lysis time, and scanning electron microscopy was performed. Increased concentrations of PS+, CD42a(+), CD142(+), CD45(+), CD14(+), and CD62P(+) EVs were found in plasma from patients with RA compared to healthy controls, and the concentrations of PS+, CD42a(+), CD14(+), and CD62P(+) EVs were positively correlated with the inflammatory parameters in RA patients. Positive correlations were also found between the levels of PS+ and CD42a(+) EVs and OCP as well as between the levels of PS+, CD42a(+), and CD62P(+)EVs and OHP. The levels of PS+, CD42a(+), CD14(+), CD62P(+), and CD62E(+) EVs were negatively correlated with OFP. Elevated levels of circulating EVs of different cell origins were found in patients with established RA, in relation to the inflammatory burden and coagulation activation in the disease.",
publisher = "Frontiers Media Sa, Lausanne",
journal = "Frontiers in Immunology",
title = "Increased Expression of Extracellular Vesicles Is Associated With the Procoagulant State in Patients With Established Rheumatoid Arthritis",
volume = "12",
doi = "10.3389/fimmu.2021.718845"
}

Stojanović, A., Veselinović, M., Zong, Y., Jakovljević, V., Pruner, I.,& Antović, A.. (2021). Increased Expression of Extracellular Vesicles Is Associated With the Procoagulant State in Patients With Established Rheumatoid Arthritis. in Frontiers in Immunology
Frontiers Media Sa, Lausanne., 12.
https://doi.org/10.3389/fimmu.2021.718845

Stojanović A, Veselinović M, Zong Y, Jakovljević V, Pruner I, Antović A. Increased Expression of Extracellular Vesicles Is Associated With the Procoagulant State in Patients With Established Rheumatoid Arthritis. in Frontiers in Immunology. 2021;12.
doi:10.3389/fimmu.2021.718845 .

Stojanović, Aleksandra, Veselinović, Mirjana, Zong, Yanan, Jakovljević, Vladimir, Pruner, Iva, Antović, Aleksandra, "Increased Expression of Extracellular Vesicles Is Associated With the Procoagulant State in Patients With Established Rheumatoid Arthritis" in Frontiers in Immunology, 12 (2021),
https://doi.org/10.3389/fimmu.2021.718845 . .

TY  - JOUR
AU  - Zong, Yanan
AU  - Pruner, Iva
AU  - Antović, Aleksandra
AU  - Taxiarchis, Apostolos
AU  - Vila, Zara Pons
AU  - Soutari, Nida
AU  - Mobarrez, Fariborz
AU  - Chaireti, Roza
AU  - Widengren, Jerker
AU  - Piguet, Joachim
AU  - Antović, Jovan P.
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1302
AB  - Circulating microparticles (MPs) are procoagulant due to the surface containing phosphatidylserine (PS), which facilitates coagulation. We investigated if MPs improve hemostasis in HA plasma models. MPs isolated from pooled normal human plasma were added to severe, moderate and mild HA plasma models (0%, 2.5%, 20% FVIII). The MPs' effect on hemostasis was evaluated by calibrated automated thrombogram (CAT) and overall hemostasis potential (OHP) assays, while fibrin structure was imaged by standard confocal, stimulated emission depletion (STED) microscopy and scanning electron microscopy (SEM). MPs partially restored thrombin generation and fibrin formation in all HA plasma models. The procoagulant effect of MPs requires PS exposure, to a less extent of contact pathway activation, but not tissue factor exposure or in vitro stimulation of MPs. MPs partially normalized the fibrin structure, and using super-resolution STED, MPs attached to fibrin were clearly resolved. In summary, our results demonstrate that PS positive MPs could improve hemostasis in HA plasma models.
PB  - Nature Portfolio, Berlin
T2  - Scientific Reports
T1  - Phosphatidylserine positive microparticles improve hemostasis in in-vitro hemophilia A plasma models
IS  - 1
VL  - 10
DO  - 10.1038/s41598-020-64686-x
ER  - 

@article{
author = "Zong, Yanan and Pruner, Iva and Antović, Aleksandra and Taxiarchis, Apostolos and Vila, Zara Pons and Soutari, Nida and Mobarrez, Fariborz and Chaireti, Roza and Widengren, Jerker and Piguet, Joachim and Antović, Jovan P.",
year = "2020",
abstract = "Circulating microparticles (MPs) are procoagulant due to the surface containing phosphatidylserine (PS), which facilitates coagulation. We investigated if MPs improve hemostasis in HA plasma models. MPs isolated from pooled normal human plasma were added to severe, moderate and mild HA plasma models (0%, 2.5%, 20% FVIII). The MPs' effect on hemostasis was evaluated by calibrated automated thrombogram (CAT) and overall hemostasis potential (OHP) assays, while fibrin structure was imaged by standard confocal, stimulated emission depletion (STED) microscopy and scanning electron microscopy (SEM). MPs partially restored thrombin generation and fibrin formation in all HA plasma models. The procoagulant effect of MPs requires PS exposure, to a less extent of contact pathway activation, but not tissue factor exposure or in vitro stimulation of MPs. MPs partially normalized the fibrin structure, and using super-resolution STED, MPs attached to fibrin were clearly resolved. In summary, our results demonstrate that PS positive MPs could improve hemostasis in HA plasma models.",
publisher = "Nature Portfolio, Berlin",
journal = "Scientific Reports",
title = "Phosphatidylserine positive microparticles improve hemostasis in in-vitro hemophilia A plasma models",
number = "1",
volume = "10",
doi = "10.1038/s41598-020-64686-x"
}

Zong, Y., Pruner, I., Antović, A., Taxiarchis, A., Vila, Z. P., Soutari, N., Mobarrez, F., Chaireti, R., Widengren, J., Piguet, J.,& Antović, J. P.. (2020). Phosphatidylserine positive microparticles improve hemostasis in in-vitro hemophilia A plasma models. in Scientific Reports
Nature Portfolio, Berlin., 10(1).
https://doi.org/10.1038/s41598-020-64686-x

Zong Y, Pruner I, Antović A, Taxiarchis A, Vila ZP, Soutari N, Mobarrez F, Chaireti R, Widengren J, Piguet J, Antović JP. Phosphatidylserine positive microparticles improve hemostasis in in-vitro hemophilia A plasma models. in Scientific Reports. 2020;10(1).
doi:10.1038/s41598-020-64686-x .

Zong, Yanan, Pruner, Iva, Antović, Aleksandra, Taxiarchis, Apostolos, Vila, Zara Pons, Soutari, Nida, Mobarrez, Fariborz, Chaireti, Roza, Widengren, Jerker, Piguet, Joachim, Antović, Jovan P., "Phosphatidylserine positive microparticles improve hemostasis in in-vitro hemophilia A plasma models" in Scientific Reports, 10, no. 1 (2020),
https://doi.org/10.1038/s41598-020-64686-x . .

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  - JOUR
AU  - Lalić-Cosić, Sanja
AU  - Dopsaj, Violeta
AU  - Kovač, Mirjana
AU  - Pruner, Iva
AU  - Littmann, Karin
AU  - Mandić-Marković, Vesna
AU  - Miković, Zeljko
AU  - Antović, Aleksandra
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1390
AB  - Introduction Haemostatic balance shifted towards hypercoagulability in normal pregnancy is even more pronounced in pre-eclampsia (P-EC). The aim of this study was to analyse haemostatic disturbances and fibrin clot properties in women with pre-eclampsia and to investigate their association with maternal and foetal outcomes. Methods Forty-six pregnant women diagnosed with pre-eclampsia were included in the study, with blood sampling done on the morning following admission to hospital, as well as after delivery (mean duration 4.8 days). Two global haemostatic assays-endogenous thrombin potential (ETP) and assay of overall haemostatic potential (OHP)-were employed, including fibrin clot turbidity measurements and scanning electron microscopy (SEM) of representative samples. Results Three thrombin generation parameters (ETP, t_lag and peak height) and OHP were significantly increased in pre-eclampsia compared with controls, whereas overall fibrinolytic potential (OFP-determined as a parameter of the OHP assay) had significantly lower values. Clot lysis time was significantly prolonged in patients with pre-eclampsia. In the pre-eclamptic group after delivery, we observed a significant elevation in the peak height and a reduction in the time to peak and OFP compared with values before delivery. Pre-eclamptic patients with renal complications had significantly higher values for ETP, peak height and D-dimer. Turbidity measurements and SEM revealed dense fibrin structure in patients with pre-eclampsia. Conclusion Patients with pre-eclampsia have enhanced coagulation and impaired fibrinolysis before, and even after, delivery. In particular, the presence of multi-organ dysfunction, such as renal dysfunction, may be associated with increased thrombin generation in pre-eclampsia.
PB  - Wiley, Hoboken
T2  - International Journal of Laboratory Hematology
T1  - Evaluation of global haemostatic assays and fibrin structure in patients with pre-eclampsia
EP  - 330
IS  - 3
SP  - 322
VL  - 42
DO  - 10.1111/ijlh.13183
ER  - 

@article{
author = "Lalić-Cosić, Sanja and Dopsaj, Violeta and Kovač, Mirjana and Pruner, Iva and Littmann, Karin and Mandić-Marković, Vesna and Miković, Zeljko and Antović, Aleksandra",
year = "2020",
abstract = "Introduction Haemostatic balance shifted towards hypercoagulability in normal pregnancy is even more pronounced in pre-eclampsia (P-EC). The aim of this study was to analyse haemostatic disturbances and fibrin clot properties in women with pre-eclampsia and to investigate their association with maternal and foetal outcomes. Methods Forty-six pregnant women diagnosed with pre-eclampsia were included in the study, with blood sampling done on the morning following admission to hospital, as well as after delivery (mean duration 4.8 days). Two global haemostatic assays-endogenous thrombin potential (ETP) and assay of overall haemostatic potential (OHP)-were employed, including fibrin clot turbidity measurements and scanning electron microscopy (SEM) of representative samples. Results Three thrombin generation parameters (ETP, t_lag and peak height) and OHP were significantly increased in pre-eclampsia compared with controls, whereas overall fibrinolytic potential (OFP-determined as a parameter of the OHP assay) had significantly lower values. Clot lysis time was significantly prolonged in patients with pre-eclampsia. In the pre-eclamptic group after delivery, we observed a significant elevation in the peak height and a reduction in the time to peak and OFP compared with values before delivery. Pre-eclamptic patients with renal complications had significantly higher values for ETP, peak height and D-dimer. Turbidity measurements and SEM revealed dense fibrin structure in patients with pre-eclampsia. Conclusion Patients with pre-eclampsia have enhanced coagulation and impaired fibrinolysis before, and even after, delivery. In particular, the presence of multi-organ dysfunction, such as renal dysfunction, may be associated with increased thrombin generation in pre-eclampsia.",
publisher = "Wiley, Hoboken",
journal = "International Journal of Laboratory Hematology",
title = "Evaluation of global haemostatic assays and fibrin structure in patients with pre-eclampsia",
pages = "330-322",
number = "3",
volume = "42",
doi = "10.1111/ijlh.13183"
}

Lalić-Cosić, S., Dopsaj, V., Kovač, M., Pruner, I., Littmann, K., Mandić-Marković, V., Miković, Z.,& Antović, A.. (2020). Evaluation of global haemostatic assays and fibrin structure in patients with pre-eclampsia. in International Journal of Laboratory Hematology
Wiley, Hoboken., 42(3), 322-330.
https://doi.org/10.1111/ijlh.13183

Lalić-Cosić S, Dopsaj V, Kovač M, Pruner I, Littmann K, Mandić-Marković V, Miković Z, Antović A. Evaluation of global haemostatic assays and fibrin structure in patients with pre-eclampsia. in International Journal of Laboratory Hematology. 2020;42(3):322-330.
doi:10.1111/ijlh.13183 .

Lalić-Cosić, Sanja, Dopsaj, Violeta, Kovač, Mirjana, Pruner, Iva, Littmann, Karin, Mandić-Marković, Vesna, Miković, Zeljko, Antović, Aleksandra, "Evaluation of global haemostatic assays and fibrin structure in patients with pre-eclampsia" in International Journal of Laboratory Hematology, 42, no. 3 (2020):322-330,
https://doi.org/10.1111/ijlh.13183 . .

TY  - JOUR
AU  - Petković, Anica
AU  - Al-Khalili, Faris
AU  - Antović, Aleksandra
AU  - Ammar, Majeed
AU  - Pruner, Iva
AU  - Vranić, Aleksandra
AU  - Soutari, Nida
AU  - Zdravković, Nebojša
AU  - Malmstrom, Rickard E.
AU  - Jakovljević, Vladimir
AU  - Antović, Jovan P.
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1345
AB  - The study was aimed to evaluate the effects of two standard doses of rivaroxaban and dabigatran on global hemostatic assays in patients with atrial fibrillation. The study included 52 patients treated with rivaroxaban (15/20 mg), 50 on dabigatran (110/150 mg) and 20 healthy individuals. Platelet-poor plasma was used for determination of three global hemostatic assays, namely endogenous thrombin potential (ETP), calibrated automated thrombogram (CAT) and overall hemostasis potential (OHP). Rivaroxaban and dabigatran reduced ETP (P lt 0.01) although OHP (P lt 0.05) was diminished only by dabigatran. Strong correlations were noticed between ETP parameters and the plasma concentrations of rivaroxaban (ETP, rUS0.51; c-max, rUS0.85; t-lag, rU0.83; t-max, rU0.66) as well as with plasma concentration of dabigatran (ETP, rUS0.75; c-max, rUS0.74; t-lag, rU0.73; t-max, rU0.52). Analysis of dabigatran concentrations under 50 ng/ml showed that ETP parameter has area under the concentration-time curvereceiver operating characteristic value of 0.879 (95% confidence interval 0.776-0.980). Dabigatran treatment paradoxically increased area under the concentration-time curve and peak values although rivaroxaban decreased peak values (P lt 0.01). However, significant correlation between CAT parameters and plasma concentration of both direct oral anticoagulants was not observed. We confirmed that the CAT assay is inappropriate for estimation of dabigatran effects and is not fully sensitive as regards rivaroxaban. The ETP assay can potentially be the appropriate method for estimation of global hemostatic capacity as regards both direct oral anticoagulants. The role of OHP needs to be confirmed in additional studies. ETP parameter of chromogenic assay has promising potential in exclusion of high plasma concentrations of dabigatran.
PB  - Lippincott Williams & Wilkins, Philadelphia
T2  - Blood Coagulation & Fibrinolysis
T1  - Effects of rivaroxaban and dabigatran on global hemostasis in patients with atrial fibrillation
EP  - 252
IS  - 4
SP  - 243
VL  - 31
DO  - 10.1097/MBC.0000000000000907
ER  - 

@article{
author = "Petković, Anica and Al-Khalili, Faris and Antović, Aleksandra and Ammar, Majeed and Pruner, Iva and Vranić, Aleksandra and Soutari, Nida and Zdravković, Nebojša and Malmstrom, Rickard E. and Jakovljević, Vladimir and Antović, Jovan P.",
year = "2020",
abstract = "The study was aimed to evaluate the effects of two standard doses of rivaroxaban and dabigatran on global hemostatic assays in patients with atrial fibrillation. The study included 52 patients treated with rivaroxaban (15/20 mg), 50 on dabigatran (110/150 mg) and 20 healthy individuals. Platelet-poor plasma was used for determination of three global hemostatic assays, namely endogenous thrombin potential (ETP), calibrated automated thrombogram (CAT) and overall hemostasis potential (OHP). Rivaroxaban and dabigatran reduced ETP (P lt 0.01) although OHP (P lt 0.05) was diminished only by dabigatran. Strong correlations were noticed between ETP parameters and the plasma concentrations of rivaroxaban (ETP, rUS0.51; c-max, rUS0.85; t-lag, rU0.83; t-max, rU0.66) as well as with plasma concentration of dabigatran (ETP, rUS0.75; c-max, rUS0.74; t-lag, rU0.73; t-max, rU0.52). Analysis of dabigatran concentrations under 50 ng/ml showed that ETP parameter has area under the concentration-time curvereceiver operating characteristic value of 0.879 (95% confidence interval 0.776-0.980). Dabigatran treatment paradoxically increased area under the concentration-time curve and peak values although rivaroxaban decreased peak values (P lt 0.01). However, significant correlation between CAT parameters and plasma concentration of both direct oral anticoagulants was not observed. We confirmed that the CAT assay is inappropriate for estimation of dabigatran effects and is not fully sensitive as regards rivaroxaban. The ETP assay can potentially be the appropriate method for estimation of global hemostatic capacity as regards both direct oral anticoagulants. The role of OHP needs to be confirmed in additional studies. ETP parameter of chromogenic assay has promising potential in exclusion of high plasma concentrations of dabigatran.",
publisher = "Lippincott Williams & Wilkins, Philadelphia",
journal = "Blood Coagulation & Fibrinolysis",
title = "Effects of rivaroxaban and dabigatran on global hemostasis in patients with atrial fibrillation",
pages = "252-243",
number = "4",
volume = "31",
doi = "10.1097/MBC.0000000000000907"
}

Petković, A., Al-Khalili, F., Antović, A., Ammar, M., Pruner, I., Vranić, A., Soutari, N., Zdravković, N., Malmstrom, R. E., Jakovljević, V.,& Antović, J. P.. (2020). Effects of rivaroxaban and dabigatran on global hemostasis in patients with atrial fibrillation. in Blood Coagulation & Fibrinolysis
Lippincott Williams & Wilkins, Philadelphia., 31(4), 243-252.
https://doi.org/10.1097/MBC.0000000000000907

Petković A, Al-Khalili F, Antović A, Ammar M, Pruner I, Vranić A, Soutari N, Zdravković N, Malmstrom RE, Jakovljević V, Antović JP. Effects of rivaroxaban and dabigatran on global hemostasis in patients with atrial fibrillation. in Blood Coagulation & Fibrinolysis. 2020;31(4):243-252.
doi:10.1097/MBC.0000000000000907 .

Petković, Anica, Al-Khalili, Faris, Antović, Aleksandra, Ammar, Majeed, Pruner, Iva, Vranić, Aleksandra, Soutari, Nida, Zdravković, Nebojša, Malmstrom, Rickard E., Jakovljević, Vladimir, Antović, Jovan P., "Effects of rivaroxaban and dabigatran on global hemostasis in patients with atrial fibrillation" in Blood Coagulation & Fibrinolysis, 31, no. 4 (2020):243-252,
https://doi.org/10.1097/MBC.0000000000000907 . .

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  - 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  - 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  - 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  - Vranić, Aleksandra
AU  - Pruner, Iva
AU  - Veselinović, Mirjana
AU  - Soutari, Nida
AU  - Petković, Anica
AU  - Jakovljević, Vladimir
AU  - Antović, Aleksandra
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1230
AB  - Objectives This study was aimed to assess hemostatic disturbances in female patients with established rheumatoid arthritis (RA) in relation to menopausal status and disease activity. Method Ninety women were included in the study, 42 patients and 48 age-matched healthy controls. There were no differences between the investigated groups regarding the presence of traditional cardiovascular risk factors. Two global hemostatic assays were employed, namely endogenous thrombin potential (ETP) and overall hemostasis potential (OHP). The parameters of the ETP assay (ETP, C-max, t-lag, t-max) and OHP assay (overall coagulation potential (OCP) and overall fibrinolytic potential (OFP)) were assessed. Moreover, the parameters of the fibrin clot (lag time, Max Abs, and slope) were measured by clot turbidity and scanning electron microscopy (SEM). Both patients and controls were divided into four subgroups according to menopause status. Results The premenopausal controls differed significantly from all other subgroups in terms of diminished levels of ETP (p = 0.02), C-max (p = 0.01), OCP (p = 0.02), OHP (p = 0.001), and Max Abs (p = 0.008), while OFP (p = 0.0001) was increased. This tendency was not seen in the premenopausal RA patients compared with the postmenopausal RA patients. SEM images showed denser clots composed of thinner fibers in samples from RA patients. The disease activity measured by DAS28 correlated with OCP and OHP (r = 0.54; p = 0.001 and r = 0.44; p = 0.003, respectively) indicating persistent hypercoagulable condition in the whole group of RA patients. Conclusions Our results point towards coagulation activation in premenopausal women with established RA. The patients were well characterized, which enabled assessment in a real-life setting.
PB  - Springer London Ltd, London
T2  - Clinical Rheumatology
T1  - Assessment of hemostatic disturbances in women with established rheumatoid arthritis
EP  - 3014
IS  - 11
SP  - 3005
VL  - 38
DO  - 10.1007/s10067-019-04629-8
ER  - 

@article{
author = "Vranić, Aleksandra and Pruner, Iva and Veselinović, Mirjana and Soutari, Nida and Petković, Anica and Jakovljević, Vladimir and Antović, Aleksandra",
year = "2019",
abstract = "Objectives This study was aimed to assess hemostatic disturbances in female patients with established rheumatoid arthritis (RA) in relation to menopausal status and disease activity. Method Ninety women were included in the study, 42 patients and 48 age-matched healthy controls. There were no differences between the investigated groups regarding the presence of traditional cardiovascular risk factors. Two global hemostatic assays were employed, namely endogenous thrombin potential (ETP) and overall hemostasis potential (OHP). The parameters of the ETP assay (ETP, C-max, t-lag, t-max) and OHP assay (overall coagulation potential (OCP) and overall fibrinolytic potential (OFP)) were assessed. Moreover, the parameters of the fibrin clot (lag time, Max Abs, and slope) were measured by clot turbidity and scanning electron microscopy (SEM). Both patients and controls were divided into four subgroups according to menopause status. Results The premenopausal controls differed significantly from all other subgroups in terms of diminished levels of ETP (p = 0.02), C-max (p = 0.01), OCP (p = 0.02), OHP (p = 0.001), and Max Abs (p = 0.008), while OFP (p = 0.0001) was increased. This tendency was not seen in the premenopausal RA patients compared with the postmenopausal RA patients. SEM images showed denser clots composed of thinner fibers in samples from RA patients. The disease activity measured by DAS28 correlated with OCP and OHP (r = 0.54; p = 0.001 and r = 0.44; p = 0.003, respectively) indicating persistent hypercoagulable condition in the whole group of RA patients. Conclusions Our results point towards coagulation activation in premenopausal women with established RA. The patients were well characterized, which enabled assessment in a real-life setting.",
publisher = "Springer London Ltd, London",
journal = "Clinical Rheumatology",
title = "Assessment of hemostatic disturbances in women with established rheumatoid arthritis",
pages = "3014-3005",
number = "11",
volume = "38",
doi = "10.1007/s10067-019-04629-8"
}

Vranić, A., Pruner, I., Veselinović, M., Soutari, N., Petković, A., Jakovljević, V.,& Antović, A.. (2019). Assessment of hemostatic disturbances in women with established rheumatoid arthritis. in Clinical Rheumatology
Springer London Ltd, London., 38(11), 3005-3014.
https://doi.org/10.1007/s10067-019-04629-8

Vranić A, Pruner I, Veselinović M, Soutari N, Petković A, Jakovljević V, Antović A. Assessment of hemostatic disturbances in women with established rheumatoid arthritis. in Clinical Rheumatology. 2019;38(11):3005-3014.
doi:10.1007/s10067-019-04629-8 .

Vranić, Aleksandra, Pruner, Iva, Veselinović, Mirjana, Soutari, Nida, Petković, Anica, Jakovljević, Vladimir, Antović, Aleksandra, "Assessment of hemostatic disturbances in women with established rheumatoid arthritis" in Clinical Rheumatology, 38, no. 11 (2019):3005-3014,
https://doi.org/10.1007/s10067-019-04629-8 . .

TY  - JOUR
AU  - Miković, Danijela
AU  - Pruner, Iva
AU  - Antović, Jovan P.
AU  - Chaireti, Roza
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1280
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Thrombosis Research
T1  - Presence of thrombophilia and levels of coagulation factors, coagulation inhibitors and TAFI do not affect global haemostasis or bleeding phenotype in patients with haemophilia A
EP  - 3
SP  - 1
VL  - 173
DO  - 10.1016/j.thromres.2018.11.008
ER  - 

@article{
author = "Miković, Danijela and Pruner, Iva and Antović, Jovan P. and Chaireti, Roza",
year = "2019",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Thrombosis Research",
title = "Presence of thrombophilia and levels of coagulation factors, coagulation inhibitors and TAFI do not affect global haemostasis or bleeding phenotype in patients with haemophilia A",
pages = "3-1",
volume = "173",
doi = "10.1016/j.thromres.2018.11.008"
}

Miković, D., Pruner, I., Antović, J. P.,& Chaireti, R.. (2019). Presence of thrombophilia and levels of coagulation factors, coagulation inhibitors and TAFI do not affect global haemostasis or bleeding phenotype in patients with haemophilia A. in Thrombosis Research
Pergamon-Elsevier Science Ltd, Oxford., 173, 1-3.
https://doi.org/10.1016/j.thromres.2018.11.008

Miković D, Pruner I, Antović JP, Chaireti R. Presence of thrombophilia and levels of coagulation factors, coagulation inhibitors and TAFI do not affect global haemostasis or bleeding phenotype in patients with haemophilia A. in Thrombosis Research. 2019;173:1-3.
doi:10.1016/j.thromres.2018.11.008 .

Miković, Danijela, Pruner, Iva, Antović, Jovan P., Chaireti, Roza, "Presence of thrombophilia and levels of coagulation factors, coagulation inhibitors and TAFI do not affect global haemostasis or bleeding phenotype in patients with haemophilia A" in Thrombosis Research, 173 (2019):1-3,
https://doi.org/10.1016/j.thromres.2018.11.008 . .

TY  - CONF
AU  - Gvozdenov, Maja
AU  - Pruner, Iva
AU  - Tomić, Branko
AU  - Kovač, Mirjana
AU  - Miljić, Predrag
AU  - Antić, Darko
AU  - Đorđević, Valentina
AU  - Radojković, Dragica
PY  - 2018
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1136
PB  - Nature Publishing Group, London
C3  - European Journal of Human Genetics
T1  - Functional analyses of the FIIc.*64_*66del gene variant and its potential role in fetal loss etiology
EP  - 828
SP  - 827
VL  - 26
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1136
ER  - 

@conference{
author = "Gvozdenov, Maja and Pruner, Iva and Tomić, Branko and Kovač, Mirjana and Miljić, Predrag and Antić, Darko and Đorđević, Valentina and Radojković, Dragica",
year = "2018",
publisher = "Nature Publishing Group, London",
journal = "European Journal of Human Genetics",
title = "Functional analyses of the FIIc.*64_*66del gene variant and its potential role in fetal loss etiology",
pages = "828-827",
volume = "26",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1136"
}

Gvozdenov, M., Pruner, I., Tomić, B., Kovač, M., Miljić, P., Antić, D., Đorđević, V.,& Radojković, D.. (2018). Functional analyses of the FIIc.*64_*66del gene variant and its potential role in fetal loss etiology. in European Journal of Human Genetics
Nature Publishing Group, London., 26, 827-828.
https://hdl.handle.net/21.15107/rcub_imagine_1136

Gvozdenov M, Pruner I, Tomić B, Kovač M, Miljić P, Antić D, Đorđević V, Radojković D. Functional analyses of the FIIc.*64_*66del gene variant and its potential role in fetal loss etiology. in European Journal of Human Genetics. 2018;26:827-828.
https://hdl.handle.net/21.15107/rcub_imagine_1136 .

Gvozdenov, Maja, Pruner, Iva, Tomić, Branko, Kovač, Mirjana, Miljić, Predrag, Antić, Darko, Đorđević, Valentina, Radojković, Dragica, "Functional analyses of the FIIc.*64_*66del gene variant and its potential role in fetal loss etiology" in European Journal of Human Genetics, 26 (2018):827-828,
https://hdl.handle.net/21.15107/rcub_imagine_1136 .

TY  - JOUR
AU  - Tomić, Branko
AU  - Gvozdenov, Maja
AU  - Pruner, Iva
AU  - Simić, Jelena M.
AU  - Kovač, Mirjana
AU  - Radojković, Dragica 
AU  - Đorđević, Valentina
PY  - 2017
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1025
AB  - Background: Deep vein thrombosis (DVT) represents a common disorder involving genetic and acquired risk factors. It has been proposed that acquired risk factors are more important with aging than genetic factors, indicating different prevalence of prothrombotic mutations throughout the lifespan. Objective: To determine the role of the most frequent prothrombotic genetic risk factors (Factor V [FV] Leiden and Factor II [FII] G20210A mutations) in first-time DVT etiology in patients of different ages. Method: This retrospective study included 701 patients living in Serbia with diagnosed DVT as a first-time thrombotic event. Results: Risk assessment for mutations as age-related markers showed no statistical difference (FV Leiden mutation-OR, 1.027; 95% confidence interval [CI],.87-1.22; P=.76 and FII G20210A mutation-OR, 0.940, 95% CI,.74-1.19; P=.61). Our results show similar mutation prevalence regardless of how old the patients were at the time of the first DVT occurrence. Conclusion: Our results indicate that these 2 mutations cannot be used as prognostic marker for time-to-event first DVT in the Serbian population; however, further studies are required.
PB  - Oxford Univ Press, Oxford
T2  - Laboratory Medicine
T1  - Are Prothrombotic Mutations a Time-to-Event Risk Factor?
EP  - 331
IS  - 4
SP  - 326
VL  - 48
DO  - 10.1093/labmed/lmx046
ER  - 

@article{
author = "Tomić, Branko and Gvozdenov, Maja and Pruner, Iva and Simić, Jelena M. and Kovač, Mirjana and Radojković, Dragica  and Đorđević, Valentina",
year = "2017",
abstract = "Background: Deep vein thrombosis (DVT) represents a common disorder involving genetic and acquired risk factors. It has been proposed that acquired risk factors are more important with aging than genetic factors, indicating different prevalence of prothrombotic mutations throughout the lifespan. Objective: To determine the role of the most frequent prothrombotic genetic risk factors (Factor V [FV] Leiden and Factor II [FII] G20210A mutations) in first-time DVT etiology in patients of different ages. Method: This retrospective study included 701 patients living in Serbia with diagnosed DVT as a first-time thrombotic event. Results: Risk assessment for mutations as age-related markers showed no statistical difference (FV Leiden mutation-OR, 1.027; 95% confidence interval [CI],.87-1.22; P=.76 and FII G20210A mutation-OR, 0.940, 95% CI,.74-1.19; P=.61). Our results show similar mutation prevalence regardless of how old the patients were at the time of the first DVT occurrence. Conclusion: Our results indicate that these 2 mutations cannot be used as prognostic marker for time-to-event first DVT in the Serbian population; however, further studies are required.",
publisher = "Oxford Univ Press, Oxford",
journal = "Laboratory Medicine",
title = "Are Prothrombotic Mutations a Time-to-Event Risk Factor?",
pages = "331-326",
number = "4",
volume = "48",
doi = "10.1093/labmed/lmx046"
}

Tomić, B., Gvozdenov, M., Pruner, I., Simić, J. M., Kovač, M., Radojković, D.,& Đorđević, V.. (2017). Are Prothrombotic Mutations a Time-to-Event Risk Factor?. in Laboratory Medicine
Oxford Univ Press, Oxford., 48(4), 326-331.
https://doi.org/10.1093/labmed/lmx046

Tomić B, Gvozdenov M, Pruner I, Simić JM, Kovač M, Radojković D, Đorđević V. Are Prothrombotic Mutations a Time-to-Event Risk Factor?. in Laboratory Medicine. 2017;48(4):326-331.
doi:10.1093/labmed/lmx046 .

Tomić, Branko, Gvozdenov, Maja, Pruner, Iva, Simić, Jelena M., Kovač, Mirjana, Radojković, Dragica , Đorđević, Valentina, "Are Prothrombotic Mutations a Time-to-Event Risk Factor?" in Laboratory Medicine, 48, no. 4 (2017):326-331,
https://doi.org/10.1093/labmed/lmx046 . .

TY  - JOUR
AU  - Miljić, Predrag
AU  - Gvozdenov, Maja
AU  - Takagi, Y.
AU  - Takagi, A.
AU  - Pruner, Iva
AU  - Dragojević, M.
AU  - Tomić, Branko
AU  - Bodrozić, J.
AU  - Kojima, T.
AU  - Radojković, Dragica
AU  - Đorđević, Valentina
PY  - 2017
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1045
AB  - Background: The recently reported c.1787G gt A mutation in the prothrombin gene leads to Arg596Gln replacement in the protein molecule (prothrombin Belgrade). This substitution impairs binding of antithrombin to thrombin and results in inherited thrombophilia, known as antithrombin resistance. Objectives: We aimed to elucidate the clinical and biochemical characteristics of thrombophilia associated with antithrombin resistance in a large Serbian family with the prothrombin Belgrade mutation. Patients and methods: Nineteen family members were investigated, among whom 10 were carriers of the c.1787G gt A mutation. In all subjects the clinical phenotype was determined and laboratory investigations of hemostatic parameters were performed. Results: Six out of the 10 mutation carriers developed thromboembolic events, mainly deep venous and mesenteric vein thrombosis. The median age of the first thrombotic event was 26.5 (12-41) years, whereas the incidence rate of first thrombosis was 2.2% per year. In all mutation carriers prothrombin activity was significantly decreased in comparison with non-carriers, clearly distinguishing each group. However, the presence of the mutation did not affect the prothrombin antigen level in plasma. The endogenous thrombin potential was significantly increased in all carriers in comparison with non-carriers, indicating the presence of blood hypercoagulability. Interestingly, levels of D-dimer and the F1+2 fragment were similar in both groups. Conclusions: Although rare, the prothrombin Belgrade mutation represents strong thrombophilia with early onset of thrombosis in the investigated family. According to our results, decreased prothrombin activity may be a simple screening test for detection of this mutation in thrombotic patients.
PB  - Wiley, Hoboken
T2  - Journal of Thrombosis and Haemostasis
T1  - Clinical and biochemical characterization of the prothrombin Belgrade mutation in a large Serbian pedigree: new insights into the antithrombin resistance mechanism
EP  - 677
IS  - 4
SP  - 670
VL  - 15
DO  - 10.1111/jth.13618
ER  - 

@article{
author = "Miljić, Predrag and Gvozdenov, Maja and Takagi, Y. and Takagi, A. and Pruner, Iva and Dragojević, M. and Tomić, Branko and Bodrozić, J. and Kojima, T. and Radojković, Dragica and Đorđević, Valentina",
year = "2017",
abstract = "Background: The recently reported c.1787G gt A mutation in the prothrombin gene leads to Arg596Gln replacement in the protein molecule (prothrombin Belgrade). This substitution impairs binding of antithrombin to thrombin and results in inherited thrombophilia, known as antithrombin resistance. Objectives: We aimed to elucidate the clinical and biochemical characteristics of thrombophilia associated with antithrombin resistance in a large Serbian family with the prothrombin Belgrade mutation. Patients and methods: Nineteen family members were investigated, among whom 10 were carriers of the c.1787G gt A mutation. In all subjects the clinical phenotype was determined and laboratory investigations of hemostatic parameters were performed. Results: Six out of the 10 mutation carriers developed thromboembolic events, mainly deep venous and mesenteric vein thrombosis. The median age of the first thrombotic event was 26.5 (12-41) years, whereas the incidence rate of first thrombosis was 2.2% per year. In all mutation carriers prothrombin activity was significantly decreased in comparison with non-carriers, clearly distinguishing each group. However, the presence of the mutation did not affect the prothrombin antigen level in plasma. The endogenous thrombin potential was significantly increased in all carriers in comparison with non-carriers, indicating the presence of blood hypercoagulability. Interestingly, levels of D-dimer and the F1+2 fragment were similar in both groups. Conclusions: Although rare, the prothrombin Belgrade mutation represents strong thrombophilia with early onset of thrombosis in the investigated family. According to our results, decreased prothrombin activity may be a simple screening test for detection of this mutation in thrombotic patients.",
publisher = "Wiley, Hoboken",
journal = "Journal of Thrombosis and Haemostasis",
title = "Clinical and biochemical characterization of the prothrombin Belgrade mutation in a large Serbian pedigree: new insights into the antithrombin resistance mechanism",
pages = "677-670",
number = "4",
volume = "15",
doi = "10.1111/jth.13618"
}

Miljić, P., Gvozdenov, M., Takagi, Y., Takagi, A., Pruner, I., Dragojević, M., Tomić, B., Bodrozić, J., Kojima, T., Radojković, D.,& Đorđević, V.. (2017). Clinical and biochemical characterization of the prothrombin Belgrade mutation in a large Serbian pedigree: new insights into the antithrombin resistance mechanism. in Journal of Thrombosis and Haemostasis
Wiley, Hoboken., 15(4), 670-677.
https://doi.org/10.1111/jth.13618

Miljić P, Gvozdenov M, Takagi Y, Takagi A, Pruner I, Dragojević M, Tomić B, Bodrozić J, Kojima T, Radojković D, Đorđević V. Clinical and biochemical characterization of the prothrombin Belgrade mutation in a large Serbian pedigree: new insights into the antithrombin resistance mechanism. in Journal of Thrombosis and Haemostasis. 2017;15(4):670-677.
doi:10.1111/jth.13618 .

Miljić, Predrag, Gvozdenov, Maja, Takagi, Y., Takagi, A., Pruner, Iva, Dragojević, M., Tomić, Branko, Bodrozić, J., Kojima, T., Radojković, Dragica, Đorđević, Valentina, "Clinical and biochemical characterization of the prothrombin Belgrade mutation in a large Serbian pedigree: new insights into the antithrombin resistance mechanism" in Journal of Thrombosis and Haemostasis, 15, no. 4 (2017):670-677,
https://doi.org/10.1111/jth.13618 . .

TY  - JOUR
AU  - Gvozdenov, Maja
AU  - Pruner, Iva
AU  - Tomić, Branko
AU  - Kovač, Mirjana
AU  - Radojković, Dragica
AU  - Đorđević, Valentina
PY  - 2017
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1055
AB  - The FII c. 1787G gt A (prothrombin Belgrade) is a novel prothrombotic mutation which leads to impaired inhibition of thrombin by antithrombin (antithrombin resistance). So far, the mechanism of this variant has not been fully elucidated. To investigate the effect of FII c. 1787G gt A mutation on the prothrombin gene expression, its functional analysis was performed in vitro. By Real-Time PCR, expression levels of FII gene variants were evaluated in Cos-7 cells transiently transfected with c. 1787G (wild-type) and c. 1787A prothrombin expression vectors, with no differences observed. The relative quantification of prothrombin protein amounts was accomplished by Western blot analysis, also with no differences observed. Therefore, the mechanism of FII c. 1787G gt A mutation does not alter prothrombin expression profile.
PB  - Maik Nauka/Interperiodica/Springer, New York
T2  - Molecular Biology
T1  - The Effect of FII c.1787G  gt  A (Prothrombin Belgrade) Mutation on Prothrombin Gene Expression In Vitro
EP  - 52
IS  - 1
SP  - 49
VL  - 51
DO  - 10.1134/S0026893316060078
ER  - 

@article{
author = "Gvozdenov, Maja and Pruner, Iva and Tomić, Branko and Kovač, Mirjana and Radojković, Dragica and Đorđević, Valentina",
year = "2017",
abstract = "The FII c. 1787G gt A (prothrombin Belgrade) is a novel prothrombotic mutation which leads to impaired inhibition of thrombin by antithrombin (antithrombin resistance). So far, the mechanism of this variant has not been fully elucidated. To investigate the effect of FII c. 1787G gt A mutation on the prothrombin gene expression, its functional analysis was performed in vitro. By Real-Time PCR, expression levels of FII gene variants were evaluated in Cos-7 cells transiently transfected with c. 1787G (wild-type) and c. 1787A prothrombin expression vectors, with no differences observed. The relative quantification of prothrombin protein amounts was accomplished by Western blot analysis, also with no differences observed. Therefore, the mechanism of FII c. 1787G gt A mutation does not alter prothrombin expression profile.",
publisher = "Maik Nauka/Interperiodica/Springer, New York",
journal = "Molecular Biology",
title = "The Effect of FII c.1787G  gt  A (Prothrombin Belgrade) Mutation on Prothrombin Gene Expression In Vitro",
pages = "52-49",
number = "1",
volume = "51",
doi = "10.1134/S0026893316060078"
}

Gvozdenov, M., Pruner, I., Tomić, B., Kovač, M., Radojković, D.,& Đorđević, V.. (2017). The Effect of FII c.1787G  gt  A (Prothrombin Belgrade) Mutation on Prothrombin Gene Expression In Vitro. in Molecular Biology
Maik Nauka/Interperiodica/Springer, New York., 51(1), 49-52.
https://doi.org/10.1134/S0026893316060078

Gvozdenov M, Pruner I, Tomić B, Kovač M, Radojković D, Đorđević V. The Effect of FII c.1787G  gt  A (Prothrombin Belgrade) Mutation on Prothrombin Gene Expression In Vitro. in Molecular Biology. 2017;51(1):49-52.
doi:10.1134/S0026893316060078 .

Gvozdenov, Maja, Pruner, Iva, Tomić, Branko, Kovač, Mirjana, Radojković, Dragica, Đorđević, Valentina, "The Effect of FII c.1787G  gt  A (Prothrombin Belgrade) Mutation on Prothrombin Gene Expression In Vitro" in Molecular Biology, 51, no. 1 (2017):49-52,
https://doi.org/10.1134/S0026893316060078 . .

TY  - JOUR
AU  - Tomić, Branko
AU  - Gvozdenov, Maja
AU  - Pruner, Iva
AU  - Kovač, Mirjana
AU  - Antonijević, Nebojša
AU  - Radojković, Dragica
AU  - Đorđević, Valentina
PY  - 2016
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/967
AB  - Venous thromboembolism is a multifactorial disorder with two manifestations: deep-vein thrombosis and pulmonary embolism. Pulmonary embolism is usually considered as the complication of deep-vein thrombosis, but there are reported cases of isolated pulmonary embolism. FV Leiden and FII G20210A mutations are most common genetic risk factors for the venous thromboembolism. Several studies reported "FV Leiden paradox": lower prevalence of FV Leiden mutation among patients with isolated pulmonary embolism than among those with deep-vein thrombosis. The aim of this study was to determine FV Leiden and FII G20210A mutations frequency in thrombophilic patients in Serbian population. We tested prevalence of these mutations carriers in 1427 individuals divided in three groups of patients (with deep-vein thrombosis, deep-vein thrombosis/pulmonary embolism and isolated pulmonary embolism) and control group. All subjects were tested for these mutations using PCR-RFLP analysis. Detected frequency of FV Leiden heterozygous carriers in patients with isolated pulmonary embolism was 6.9% (for FII G20210A 11.6%), while in other two groups of patients with deep-vein thrombosis and deep vein thrombosis/pulmonary embolism, frequency was 18.6% (for FII G20210A mutation were 11.6% and 8.3%, respectively). Our results showed that FV Leiden mutation is less frequent in patients with isolated pulmonary embolism than in patients with deep-vein thrombosis or deep-vein thrombosis accompanied with pulmonary embolism, confirming "FV Leiden paradox". On the other hand, detected frequency of FII G20210A mutation carriers was similar in all three groups of patients.
PB  - Društvo genetičara Srbije, Beograd
T2  - Genetika-Belgrade
T1  - The frequencies of fv leiden and fii g20210a mutations in patients with different clinical manifestations of venous thromboembolism: experience from large Serbian cohort
EP  - 616
IS  - 2
SP  - 609
VL  - 48
DO  - 10.2298/GENSR1602609T
ER  - 

@article{
author = "Tomić, Branko and Gvozdenov, Maja and Pruner, Iva and Kovač, Mirjana and Antonijević, Nebojša and Radojković, Dragica and Đorđević, Valentina",
year = "2016",
abstract = "Venous thromboembolism is a multifactorial disorder with two manifestations: deep-vein thrombosis and pulmonary embolism. Pulmonary embolism is usually considered as the complication of deep-vein thrombosis, but there are reported cases of isolated pulmonary embolism. FV Leiden and FII G20210A mutations are most common genetic risk factors for the venous thromboembolism. Several studies reported "FV Leiden paradox": lower prevalence of FV Leiden mutation among patients with isolated pulmonary embolism than among those with deep-vein thrombosis. The aim of this study was to determine FV Leiden and FII G20210A mutations frequency in thrombophilic patients in Serbian population. We tested prevalence of these mutations carriers in 1427 individuals divided in three groups of patients (with deep-vein thrombosis, deep-vein thrombosis/pulmonary embolism and isolated pulmonary embolism) and control group. All subjects were tested for these mutations using PCR-RFLP analysis. Detected frequency of FV Leiden heterozygous carriers in patients with isolated pulmonary embolism was 6.9% (for FII G20210A 11.6%), while in other two groups of patients with deep-vein thrombosis and deep vein thrombosis/pulmonary embolism, frequency was 18.6% (for FII G20210A mutation were 11.6% and 8.3%, respectively). Our results showed that FV Leiden mutation is less frequent in patients with isolated pulmonary embolism than in patients with deep-vein thrombosis or deep-vein thrombosis accompanied with pulmonary embolism, confirming "FV Leiden paradox". On the other hand, detected frequency of FII G20210A mutation carriers was similar in all three groups of patients.",
publisher = "Društvo genetičara Srbije, Beograd",
journal = "Genetika-Belgrade",
title = "The frequencies of fv leiden and fii g20210a mutations in patients with different clinical manifestations of venous thromboembolism: experience from large Serbian cohort",
pages = "616-609",
number = "2",
volume = "48",
doi = "10.2298/GENSR1602609T"
}

Tomić, B., Gvozdenov, M., Pruner, I., Kovač, M., Antonijević, N., Radojković, D.,& Đorđević, V.. (2016). The frequencies of fv leiden and fii g20210a mutations in patients with different clinical manifestations of venous thromboembolism: experience from large Serbian cohort. in Genetika-Belgrade
Društvo genetičara Srbije, Beograd., 48(2), 609-616.
https://doi.org/10.2298/GENSR1602609T

Tomić B, Gvozdenov M, Pruner I, Kovač M, Antonijević N, Radojković D, Đorđević V. The frequencies of fv leiden and fii g20210a mutations in patients with different clinical manifestations of venous thromboembolism: experience from large Serbian cohort. in Genetika-Belgrade. 2016;48(2):609-616.
doi:10.2298/GENSR1602609T .

Tomić, Branko, Gvozdenov, Maja, Pruner, Iva, Kovač, Mirjana, Antonijević, Nebojša, Radojković, Dragica, Đorđević, Valentina, "The frequencies of fv leiden and fii g20210a mutations in patients with different clinical manifestations of venous thromboembolism: experience from large Serbian cohort" in Genetika-Belgrade, 48, no. 2 (2016):609-616,
https://doi.org/10.2298/GENSR1602609T . .

TY  - CONF
AU  - Miljić, P.
AU  - Bodrozić, J.
AU  - Pruner, Iva
AU  - Đorđević, Valentina
PY  - 2016
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/956
PB  - Wiley-Blackwell, Hoboken
C3  - Journal of Thrombosis and Haemostasis
T1  - Antithrombin resistance caused by c.1787G  gt  a mutation in prothrombin gene: rare but strong inherited thrombophilia
EP  - 97
SP  - 97
VL  - 14
UR  - https://hdl.handle.net/21.15107/rcub_imagine_956
ER  - 

@conference{
author = "Miljić, P. and Bodrozić, J. and Pruner, Iva and Đorđević, Valentina",
year = "2016",
publisher = "Wiley-Blackwell, Hoboken",
journal = "Journal of Thrombosis and Haemostasis",
title = "Antithrombin resistance caused by c.1787G  gt  a mutation in prothrombin gene: rare but strong inherited thrombophilia",
pages = "97-97",
volume = "14",
url = "https://hdl.handle.net/21.15107/rcub_imagine_956"
}

Miljić, P., Bodrozić, J., Pruner, I.,& Đorđević, V.. (2016). Antithrombin resistance caused by c.1787G  gt  a mutation in prothrombin gene: rare but strong inherited thrombophilia. in Journal of Thrombosis and Haemostasis
Wiley-Blackwell, Hoboken., 14, 97-97.
https://hdl.handle.net/21.15107/rcub_imagine_956

Miljić P, Bodrozić J, Pruner I, Đorđević V. Antithrombin resistance caused by c.1787G  gt  a mutation in prothrombin gene: rare but strong inherited thrombophilia. in Journal of Thrombosis and Haemostasis. 2016;14:97-97.
https://hdl.handle.net/21.15107/rcub_imagine_956 .

Miljić, P., Bodrozić, J., Pruner, Iva, Đorđević, Valentina, "Antithrombin resistance caused by c.1787G  gt  a mutation in prothrombin gene: rare but strong inherited thrombophilia" in Journal of Thrombosis and Haemostasis, 14 (2016):97-97,
https://hdl.handle.net/21.15107/rcub_imagine_956 .

TY  - CONF
AU  - Kovač, Mirjana
AU  - Kovac, Z.
AU  - Tomasević, Z.
AU  - Pruner, Iva
AU  - Tomić, Branko
AU  - Đorđević, Valentina
AU  - Radojković, Dragica
PY  - 2016
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/964
PB  - Wiley-Blackwell, Hoboken
C3  - Journal of Thrombosis and Haemostasis
T1  - High Factor VIII and advanced disease are associated with risk of recurrent thrombosis in women with breast cancer
EP  - 164
SP  - 164
VL  - 14
UR  - https://hdl.handle.net/21.15107/rcub_imagine_964
ER  - 

@conference{
author = "Kovač, Mirjana and Kovac, Z. and Tomasević, Z. and Pruner, Iva and Tomić, Branko and Đorđević, Valentina and Radojković, Dragica",
year = "2016",
publisher = "Wiley-Blackwell, Hoboken",
journal = "Journal of Thrombosis and Haemostasis",
title = "High Factor VIII and advanced disease are associated with risk of recurrent thrombosis in women with breast cancer",
pages = "164-164",
volume = "14",
url = "https://hdl.handle.net/21.15107/rcub_imagine_964"
}

Kovač, M., Kovac, Z., Tomasević, Z., Pruner, I., Tomić, B., Đorđević, V.,& Radojković, D.. (2016). High Factor VIII and advanced disease are associated with risk of recurrent thrombosis in women with breast cancer. in Journal of Thrombosis and Haemostasis
Wiley-Blackwell, Hoboken., 14, 164-164.
https://hdl.handle.net/21.15107/rcub_imagine_964

Kovač M, Kovac Z, Tomasević Z, Pruner I, Tomić B, Đorđević V, Radojković D. High Factor VIII and advanced disease are associated with risk of recurrent thrombosis in women with breast cancer. in Journal of Thrombosis and Haemostasis. 2016;14:164-164.
https://hdl.handle.net/21.15107/rcub_imagine_964 .

Kovač, Mirjana, Kovac, Z., Tomasević, Z., Pruner, Iva, Tomić, Branko, Đorđević, Valentina, Radojković, Dragica, "High Factor VIII and advanced disease are associated with risk of recurrent thrombosis in women with breast cancer" in Journal of Thrombosis and Haemostasis, 14 (2016):164-164,
https://hdl.handle.net/21.15107/rcub_imagine_964 .

TY  - JOUR
AU  - Gvozdenov, Maja
AU  - Pruner, Iva
AU  - Tomić, Branko
AU  - Aradjanski, Marijana
AU  - Antonijević, Nebojša
AU  - Radojković, Dragica
AU  - Đorđević, Valentina
PY  - 2015
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/871
AB  - Objective Pulmonary embolism is usually considered as a complication of deep vein thrombosis, but there are still a number of cases of isolated pulmonary embolism. We aimed to investigate whether prothrombin 3’ end gene variants might play a signifi cant role in the pathogenesis of isolated pulmonary embolism. Methods and results In this study 100 patients with isolated pulmonary embolism and 100 controls were screened by DNA sequencing. Screening included last intron, last exon, 3’UTR and part of the 3’FR region of the prothrombin gene. Our results have shown that heterozygous carriers of the FII G20210A variant have a signifi cantly higher risk of isolated pulmonary embolism (OR 4.83; 95%CI 1.33-17.52; P = 0.02). Carriers of the FII 19911GG genotype (OR 1.41; 95%CI 0.72-2.73; P = 0.31) and FII 20068CT genotype (OR 3.06; 95%CI 0.31-29.95; P = 0.34) were more frequent in patients with isolated pulmonary embolism compared to controls. We also detected the novel gene variants, FIIc.*64_*66del and FII c.*303T gt C, in two patients. Conclusions Our results suggest that FII G20210A represents a signifi cant risk factor for isolated pulmonary embolism. The FII G19911A and FII C20068T are potentially associated with an increased risk for the occurrence of isolated pulmonary embolism, but the results did not reach statistical signifi cance. This is the fi rst study in which the two novel 3’ end prothrombin gene variants, FIIc.*64_*66del and FII c.*303T gt C, were reported.
PB  - Acta Cardiologica
T2  - Acta Cardiologica
T1  - Prothrombin 3’ end gene variants in isolated pulmonary embolism – The first report of FIIc.*64_*66del and FIIc.*303T gt C variants
EP  - 182
IS  - 2
SP  - 177
VL  - 70
DO  - 10.2143/AC.70.2.3073509
ER  - 

@article{
author = "Gvozdenov, Maja and Pruner, Iva and Tomić, Branko and Aradjanski, Marijana and Antonijević, Nebojša and Radojković, Dragica and Đorđević, Valentina",
year = "2015",
abstract = "Objective Pulmonary embolism is usually considered as a complication of deep vein thrombosis, but there are still a number of cases of isolated pulmonary embolism. We aimed to investigate whether prothrombin 3’ end gene variants might play a signifi cant role in the pathogenesis of isolated pulmonary embolism. Methods and results In this study 100 patients with isolated pulmonary embolism and 100 controls were screened by DNA sequencing. Screening included last intron, last exon, 3’UTR and part of the 3’FR region of the prothrombin gene. Our results have shown that heterozygous carriers of the FII G20210A variant have a signifi cantly higher risk of isolated pulmonary embolism (OR 4.83; 95%CI 1.33-17.52; P = 0.02). Carriers of the FII 19911GG genotype (OR 1.41; 95%CI 0.72-2.73; P = 0.31) and FII 20068CT genotype (OR 3.06; 95%CI 0.31-29.95; P = 0.34) were more frequent in patients with isolated pulmonary embolism compared to controls. We also detected the novel gene variants, FIIc.*64_*66del and FII c.*303T gt C, in two patients. Conclusions Our results suggest that FII G20210A represents a signifi cant risk factor for isolated pulmonary embolism. The FII G19911A and FII C20068T are potentially associated with an increased risk for the occurrence of isolated pulmonary embolism, but the results did not reach statistical signifi cance. This is the fi rst study in which the two novel 3’ end prothrombin gene variants, FIIc.*64_*66del and FII c.*303T gt C, were reported.",
publisher = "Acta Cardiologica",
journal = "Acta Cardiologica",
title = "Prothrombin 3’ end gene variants in isolated pulmonary embolism – The first report of FIIc.*64_*66del and FIIc.*303T gt C variants",
pages = "182-177",
number = "2",
volume = "70",
doi = "10.2143/AC.70.2.3073509"
}

Gvozdenov, M., Pruner, I., Tomić, B., Aradjanski, M., Antonijević, N., Radojković, D.,& Đorđević, V.. (2015). Prothrombin 3’ end gene variants in isolated pulmonary embolism – The first report of FIIc.*64_*66del and FIIc.*303T gt C variants. in Acta Cardiologica
Acta Cardiologica., 70(2), 177-182.
https://doi.org/10.2143/AC.70.2.3073509

Gvozdenov M, Pruner I, Tomić B, Aradjanski M, Antonijević N, Radojković D, Đorđević V. Prothrombin 3’ end gene variants in isolated pulmonary embolism – The first report of FIIc.*64_*66del and FIIc.*303T gt C variants. in Acta Cardiologica. 2015;70(2):177-182.
doi:10.2143/AC.70.2.3073509 .

Gvozdenov, Maja, Pruner, Iva, Tomić, Branko, Aradjanski, Marijana, Antonijević, Nebojša, Radojković, Dragica, Đorđević, Valentina, "Prothrombin 3’ end gene variants in isolated pulmonary embolism – The first report of FIIc.*64_*66del and FIIc.*303T gt C variants" in Acta Cardiologica, 70, no. 2 (2015):177-182,
https://doi.org/10.2143/AC.70.2.3073509 . .

TY  - JOUR
AU  - Pruner, Iva
AU  - Đorđević, Valentina
AU  - Gvozdenov, Maja
AU  - Tomić, Branko
AU  - Kovač, Mirjana
AU  - Miljić, Predrag
AU  - Radojković, Dragica
PY  - 2015
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/830
AB  - Recurrent pregnancy loss (RPL) is a health problem affecting up to 5% of women of reproductive age. Several thrombophilic risk factors might contribute to RPL. To investigate relationship between a novel C20068T gene variant in the 3' end of prothrombin gene and RPL, we tested 153 women with RPL and 111 controls for the presence of this gene variant. In patients, we have detected four heterozygous (2.61%) and no homozygous carriers. In controls, no carriers were detected. Our results indicate higher prevalence of C20068T gene variant in women with RPL but this difference was not statistically significant. However, in patients who suffered 5 or more RPL, frequency of C20068T gene variant was significantly increased compared to controls (12.5% vs. 0%, P = 0.02). This is the first study which points out a possible role of C20068T gene variant in etiology of RPL, but larger studies should be carried out to confirm our findings.
PB  - Društvo genetičara Srbije, Beograd
T2  - Genetika-Belgrade
T1  - The c20068t gene variant in the 3 ' end of the prothrombin gene and recurrent pregnancy loss: a pilot study
EP  - 476
IS  - 2
SP  - 469
VL  - 47
DO  - 10.2298/GENSR1502469P
ER  - 

@article{
author = "Pruner, Iva and Đorđević, Valentina and Gvozdenov, Maja and Tomić, Branko and Kovač, Mirjana and Miljić, Predrag and Radojković, Dragica",
year = "2015",
abstract = "Recurrent pregnancy loss (RPL) is a health problem affecting up to 5% of women of reproductive age. Several thrombophilic risk factors might contribute to RPL. To investigate relationship between a novel C20068T gene variant in the 3' end of prothrombin gene and RPL, we tested 153 women with RPL and 111 controls for the presence of this gene variant. In patients, we have detected four heterozygous (2.61%) and no homozygous carriers. In controls, no carriers were detected. Our results indicate higher prevalence of C20068T gene variant in women with RPL but this difference was not statistically significant. However, in patients who suffered 5 or more RPL, frequency of C20068T gene variant was significantly increased compared to controls (12.5% vs. 0%, P = 0.02). This is the first study which points out a possible role of C20068T gene variant in etiology of RPL, but larger studies should be carried out to confirm our findings.",
publisher = "Društvo genetičara Srbije, Beograd",
journal = "Genetika-Belgrade",
title = "The c20068t gene variant in the 3 ' end of the prothrombin gene and recurrent pregnancy loss: a pilot study",
pages = "476-469",
number = "2",
volume = "47",
doi = "10.2298/GENSR1502469P"
}

Pruner, I., Đorđević, V., Gvozdenov, M., Tomić, B., Kovač, M., Miljić, P.,& Radojković, D.. (2015). The c20068t gene variant in the 3 ' end of the prothrombin gene and recurrent pregnancy loss: a pilot study. in Genetika-Belgrade
Društvo genetičara Srbije, Beograd., 47(2), 469-476.
https://doi.org/10.2298/GENSR1502469P

Pruner I, Đorđević V, Gvozdenov M, Tomić B, Kovač M, Miljić P, Radojković D. The c20068t gene variant in the 3 ' end of the prothrombin gene and recurrent pregnancy loss: a pilot study. in Genetika-Belgrade. 2015;47(2):469-476.
doi:10.2298/GENSR1502469P .

Pruner, Iva, Đorđević, Valentina, Gvozdenov, Maja, Tomić, Branko, Kovač, Mirjana, Miljić, Predrag, Radojković, Dragica, "The c20068t gene variant in the 3 ' end of the prothrombin gene and recurrent pregnancy loss: a pilot study" in Genetika-Belgrade, 47, no. 2 (2015):469-476,
https://doi.org/10.2298/GENSR1502469P . .