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

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

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

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

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

TY  - JOUR
AU  - Backović, Dragana
AU  - Ignjatović, Svetlana
AU  - Rakićević, Ljiljana
AU  - Novković, Mirjana
AU  - Kušić-Tišma, Jelena
AU  - Radojković, Dragica
AU  - Strugarević, Evgenija
AU  - Calija, Branko
AU  - Radak, Djordje
AU  - Kovač, Mirjana
PY  - 2016
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/920
AB  - Objectives: A considerable number of patients do not achieve an adequate response to clopidogrel. Our study aimed to evaluate genetic and non-genetic factors as possible risks for clopidogrel high on-treatment platelet reactivity (HTPR) in patients (n=112) with carotid artery stenosis undergoing endarterectomy (CEA). Methods: Using multiple-electrode impedance aggregometry (MEA) the antiplatelet effectiveness of clopidogrel was measured after 24 h, 7 and 30 days of clopidogrel treatment, which was introduced after elective CEA at a dose of 75 mg daily, for at least 30 days. Results: HTPR was observed among 25% patients after clopidogrel therapy for 30 days. Further analysis showed that 53.3% of patients carrying the CYP2C19*2 gene variant had clopidogrel-HTPR, while in the wild type group there were 14.6% (p lt 0.001). Multivariate logistic regression analysis identified the CYP2C19*2 variant allele (OR 4.384; 95% CI 1.296-14.833, p=0.017) and high total cholesterol level (OR 2.090; 95% CI 1.263-3.459, p=0.004) as the only independent risk factors for clopidogrel-HTPR. Conclusion: The CYP2C19*2 gene variant and high total cholesterol level were major factors for clopidogrel-HTPR in patients with carotid artery stenosis undergoing CEA.
PB  - Bentham Science Publ Ltd, Sharjah
T2  - Current Vascular Pharmacology
T1  - Clopidogrel High On-Treatment Platelet Reactivity in Patients with Carotid Artery Stenosis Undergoing Endarterectomy. A Pilot Study
EP  - 569
IS  - 6
SP  - 563
VL  - 14
DO  - 10.2174/1570161114666160714103148
ER  - 

@article{
author = "Backović, Dragana and Ignjatović, Svetlana and Rakićević, Ljiljana and Novković, Mirjana and Kušić-Tišma, Jelena and Radojković, Dragica and Strugarević, Evgenija and Calija, Branko and Radak, Djordje and Kovač, Mirjana",
year = "2016",
abstract = "Objectives: A considerable number of patients do not achieve an adequate response to clopidogrel. Our study aimed to evaluate genetic and non-genetic factors as possible risks for clopidogrel high on-treatment platelet reactivity (HTPR) in patients (n=112) with carotid artery stenosis undergoing endarterectomy (CEA). Methods: Using multiple-electrode impedance aggregometry (MEA) the antiplatelet effectiveness of clopidogrel was measured after 24 h, 7 and 30 days of clopidogrel treatment, which was introduced after elective CEA at a dose of 75 mg daily, for at least 30 days. Results: HTPR was observed among 25% patients after clopidogrel therapy for 30 days. Further analysis showed that 53.3% of patients carrying the CYP2C19*2 gene variant had clopidogrel-HTPR, while in the wild type group there were 14.6% (p lt 0.001). Multivariate logistic regression analysis identified the CYP2C19*2 variant allele (OR 4.384; 95% CI 1.296-14.833, p=0.017) and high total cholesterol level (OR 2.090; 95% CI 1.263-3.459, p=0.004) as the only independent risk factors for clopidogrel-HTPR. Conclusion: The CYP2C19*2 gene variant and high total cholesterol level were major factors for clopidogrel-HTPR in patients with carotid artery stenosis undergoing CEA.",
publisher = "Bentham Science Publ Ltd, Sharjah",
journal = "Current Vascular Pharmacology",
title = "Clopidogrel High On-Treatment Platelet Reactivity in Patients with Carotid Artery Stenosis Undergoing Endarterectomy. A Pilot Study",
pages = "569-563",
number = "6",
volume = "14",
doi = "10.2174/1570161114666160714103148"
}

Backović, D., Ignjatović, S., Rakićević, L., Novković, M., Kušić-Tišma, J., Radojković, D., Strugarević, E., Calija, B., Radak, D.,& Kovač, M.. (2016). Clopidogrel High On-Treatment Platelet Reactivity in Patients with Carotid Artery Stenosis Undergoing Endarterectomy. A Pilot Study. in Current Vascular Pharmacology
Bentham Science Publ Ltd, Sharjah., 14(6), 563-569.
https://doi.org/10.2174/1570161114666160714103148

Backović D, Ignjatović S, Rakićević L, Novković M, Kušić-Tišma J, Radojković D, Strugarević E, Calija B, Radak D, Kovač M. Clopidogrel High On-Treatment Platelet Reactivity in Patients with Carotid Artery Stenosis Undergoing Endarterectomy. A Pilot Study. in Current Vascular Pharmacology. 2016;14(6):563-569.
doi:10.2174/1570161114666160714103148 .

Backović, Dragana, Ignjatović, Svetlana, Rakićević, Ljiljana, Novković, Mirjana, Kušić-Tišma, Jelena, Radojković, Dragica, Strugarević, Evgenija, Calija, Branko, Radak, Djordje, Kovač, Mirjana, "Clopidogrel High On-Treatment Platelet Reactivity in Patients with Carotid Artery Stenosis Undergoing Endarterectomy. A Pilot Study" in Current Vascular Pharmacology, 14, no. 6 (2016):563-569,
https://doi.org/10.2174/1570161114666160714103148 . .

TY  - JOUR
AU  - Rakićević, Ljiljana
AU  - Kušić-Tišma, Jelena
AU  - Kovač, Mirjana
AU  - Backović, Dragana
AU  - Radojković, Dragica 
PY  - 2013
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/651
AB  - During the last decade genetic factors affecting coumarin therapy have been extensively investigated. The most important genes appear to be CYP2C9 and VKORC1, and different studies have shown that DNA testing can dramatically improve the safety and effectiveness of the therapy. However, the implementation of pharmacogenetic testing in everyday practice is still not a reality. Facilities and ability to get results before the start of therapy are very important. The implementation of specific methodology and equipment for particular type of diagnostics can represent a serious, even impossible, financial hurdle to overcome (especially in developing countries). For this reason, the use of every tool that contributes to rationalization of the existing methods can be a considerable asset. Therefore, we set the goal to rationalize our current DNA sequencing based protocol for analysis of the VKORC1 c.-1639G gt A, CYP2C9*2 and CYP2C9*3 variant alleles, in order to obtain shorter and easier procedure. Simplification of the protocol was achieved by setting up multiplex PCR and omitting DNA extraction. This rationalization of the existing DNA sequencing based procedure allows getting results in 12 hours. The new protocol was tested on 118 samples. Obtained results have shown full accordance to those obtained with previous, non-modified protocol. Therefore, given the circumstances, we consider that protocol for pharmocogenetic testing should be made more accessible - both to doctors and patients. It is one of the prerequisites in order to make genotyping prior to the therapy common practice.
PB  - Taylor & Francis Ltd, Abingdon
T2  - Scandinavian Journal of Clinical & Laboratory Investigation
T1  - Rationalized DNA sequencing-based protocol for genotyping patients receiving coumarin therapy
EP  - 527
IS  - 6
SP  - 523
VL  - 73
DO  - 10.3109/00365513.2013.809142
ER  - 

@article{
author = "Rakićević, Ljiljana and Kušić-Tišma, Jelena and Kovač, Mirjana and Backović, Dragana and Radojković, Dragica ",
year = "2013",
abstract = "During the last decade genetic factors affecting coumarin therapy have been extensively investigated. The most important genes appear to be CYP2C9 and VKORC1, and different studies have shown that DNA testing can dramatically improve the safety and effectiveness of the therapy. However, the implementation of pharmacogenetic testing in everyday practice is still not a reality. Facilities and ability to get results before the start of therapy are very important. The implementation of specific methodology and equipment for particular type of diagnostics can represent a serious, even impossible, financial hurdle to overcome (especially in developing countries). For this reason, the use of every tool that contributes to rationalization of the existing methods can be a considerable asset. Therefore, we set the goal to rationalize our current DNA sequencing based protocol for analysis of the VKORC1 c.-1639G gt A, CYP2C9*2 and CYP2C9*3 variant alleles, in order to obtain shorter and easier procedure. Simplification of the protocol was achieved by setting up multiplex PCR and omitting DNA extraction. This rationalization of the existing DNA sequencing based procedure allows getting results in 12 hours. The new protocol was tested on 118 samples. Obtained results have shown full accordance to those obtained with previous, non-modified protocol. Therefore, given the circumstances, we consider that protocol for pharmocogenetic testing should be made more accessible - both to doctors and patients. It is one of the prerequisites in order to make genotyping prior to the therapy common practice.",
publisher = "Taylor & Francis Ltd, Abingdon",
journal = "Scandinavian Journal of Clinical & Laboratory Investigation",
title = "Rationalized DNA sequencing-based protocol for genotyping patients receiving coumarin therapy",
pages = "527-523",
number = "6",
volume = "73",
doi = "10.3109/00365513.2013.809142"
}

Rakićević, L., Kušić-Tišma, J., Kovač, M., Backović, D.,& Radojković, D.. (2013). Rationalized DNA sequencing-based protocol for genotyping patients receiving coumarin therapy. in Scandinavian Journal of Clinical & Laboratory Investigation
Taylor & Francis Ltd, Abingdon., 73(6), 523-527.
https://doi.org/10.3109/00365513.2013.809142

Rakićević L, Kušić-Tišma J, Kovač M, Backović D, Radojković D. Rationalized DNA sequencing-based protocol for genotyping patients receiving coumarin therapy. in Scandinavian Journal of Clinical & Laboratory Investigation. 2013;73(6):523-527.
doi:10.3109/00365513.2013.809142 .

Rakićević, Ljiljana, Kušić-Tišma, Jelena, Kovač, Mirjana, Backović, Dragana, Radojković, Dragica , "Rationalized DNA sequencing-based protocol for genotyping patients receiving coumarin therapy" in Scandinavian Journal of Clinical & Laboratory Investigation, 73, no. 6 (2013):523-527,
https://doi.org/10.3109/00365513.2013.809142 . .