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  - Đorđević, Valentina
AU  - Kovač, Mirjana
AU  - Miljić, Predrag
AU  - Murata, M.
AU  - Takagi, A.
AU  - Pruner, Iva
AU  - Francuski, D.
AU  - Kojima, T.
AU  - Radojković, Dragica
PY  - 2013
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/629
PB  - Wiley-Blackwell, Hoboken
T2  - Journal of Thrombosis and Haemostasis
T1  - A novel prothrombin mutation in two families with prominent thrombophilia - the first cases of antithrombin resistance in a Caucasian population
EP  - 1939
IS  - 10
SP  - 1936
VL  - 11
DO  - 10.1111/jth.12367
ER  - 

@article{
author = "Đorđević, Valentina and Kovač, Mirjana and Miljić, Predrag and Murata, M. and Takagi, A. and Pruner, Iva and Francuski, D. and Kojima, T. and Radojković, Dragica",
year = "2013",
publisher = "Wiley-Blackwell, Hoboken",
journal = "Journal of Thrombosis and Haemostasis",
title = "A novel prothrombin mutation in two families with prominent thrombophilia - the first cases of antithrombin resistance in a Caucasian population",
pages = "1939-1936",
number = "10",
volume = "11",
doi = "10.1111/jth.12367"
}

Đorđević, V., Kovač, M., Miljić, P., Murata, M., Takagi, A., Pruner, I., Francuski, D., Kojima, T.,& Radojković, D.. (2013). A novel prothrombin mutation in two families with prominent thrombophilia - the first cases of antithrombin resistance in a Caucasian population. in Journal of Thrombosis and Haemostasis
Wiley-Blackwell, Hoboken., 11(10), 1936-1939.
https://doi.org/10.1111/jth.12367

Đorđević V, Kovač M, Miljić P, Murata M, Takagi A, Pruner I, Francuski D, Kojima T, Radojković D. A novel prothrombin mutation in two families with prominent thrombophilia - the first cases of antithrombin resistance in a Caucasian population. in Journal of Thrombosis and Haemostasis. 2013;11(10):1936-1939.
doi:10.1111/jth.12367 .

Đorđević, Valentina, Kovač, Mirjana, Miljić, Predrag, Murata, M., Takagi, A., Pruner, Iva, Francuski, D., Kojima, T., Radojković, Dragica, "A novel prothrombin mutation in two families with prominent thrombophilia - the first cases of antithrombin resistance in a Caucasian population" in Journal of Thrombosis and Haemostasis, 11, no. 10 (2013):1936-1939,
https://doi.org/10.1111/jth.12367 . .