TY  - JOUR
AU  - Stanković, Marija
AU  - Đorđević, Valentina
AU  - Tomović, Valentina
AU  - Nagorni-Obradović, Ljudmila
AU  - Petrović-Stanojević, Nataša
AU  - Kovač, Mirjana
AU  - Radojković, Dragica
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1654
AB  - Background: Chronic  obstructive  pulmonary  disease(COPD) is a complex disorder with unexplained heritability.Interactions  of  genetic  and  environmental  factors  arethought  to  be  crucial  in  COPD.  So,  we  aim  to  examineinteractions of the endothelial nitric oxide synthase (eNOS)and angiotensin converting enzyme (ACE) genes and ciga-rette smoking in COPD. Methods:The  eNOS  G894T  and  ACE  ID  variants  wereanalyzed  in  122  COPD  patients  and  200  controls  fromSerbia. The effect of the variants on COPD was assessed bylogistic  regression.  Interactions  between  eNOS,  ACE  andcigarette  smoking  in  COPD  were  evaluated  using  a  case-control model. Interaction between the genes was analyzedin silico. Results:No effect of the eNOS G894T and ACE ID variantson  COPD  was  found  in  our  study.  Gene-gene  interactionbetween  the  eNOS  TT  and  ACE  D  was  identified(p=0.033) in COPD. The interaction is realized within the complex network of biochemical pathways. Gene-environ-ment  interactions  between  the  eNOS  T  and  cigarettesmoking (p=0.013), and the ACE II and cigarette smoking(p=0.009) were detected in COPD in our study. Conclusions:This is the first research to reveal interactionsof  the  eNOS  and  ACE  genes  and  cigarette  smoking  inCOPD progressing our understanding of COPD heritabilityand contributing to the development of appropriate treat-ments.
AB  - Uvod: Hronična opstruktivna bolest pluća (HOBP) je složeno oboljenje sa nerazjašnjenom genetičkom osnovom.Smatra se da su interakcije genetskih i spoljašnjih faktora ključne u HOBP. Stoga je naš cilj bio da ispitamo interakcijegena za endotelijalnu azot-monoksid sintazu (eNOS) i angiotenzin konvertujući enzim (ACE) i duvanskog dima uHOBP. Metode :eNOS G894T i ACE ID varijante su analiziranekod 122 HOBP pacijenta i 200 kontrola iz Srbije. Uticajvarijanti na HOBP je ispitan logističkom regresijom. Interakcije izme|u eNOS, ACE i duvanskog dima u HOBP suispitane korišćenjem modela slučaj-kontrola. Interakciaja između gena je analizirana in silico. Rezultati: Prema ovoj studiji eNOS G894T i ACE ID varijante nemaju uticaj na HOBP. Gen-gen interakcija između eNOS TT i ACE D je identifikovana (p=0,033) u HOBP.Ova interakcija se ostvaruje u okviru složene mreže bio-hemijskih puteva. Gen-sredina interakcije izme|u eNOS Ti duvanskog dima (p=0,013), i ACE II i duvanskog dima(p=0,009) su detektovane u HOBP u ovoj studiji.Zaključak: Ovo je prvo istraživanje u kome su otkriveneinterakcije između eNOS i ACE gena i duvanskog dima uHOBP što doprinosi našem razumevanju genetičke osnove HOBP i razvoju adekvatnog tretmana.
PB  - Belgrade : Society of Medical Biochemists of Serbia
T2  - Journal of Medical Biochemistry
T1  - Interactions of the eNOS and ACE genes and cigarette smoking in chronic obstructive pulmonary disease
T1  - Interakcije eNOS i ACE gena i duvanskog dima u hroničnoj opstruktivnoj bolesti pluća
EP  - 104
IS  - 1
SP  - 94
VL  - 41
DO  - 10.5937/jomb0-34017
ER  - 

@article{
author = "Stanković, Marija and Đorđević, Valentina and Tomović, Valentina and Nagorni-Obradović, Ljudmila and Petrović-Stanojević, Nataša and Kovač, Mirjana and Radojković, Dragica",
year = "2023",
abstract = "Background: Chronic  obstructive  pulmonary  disease(COPD) is a complex disorder with unexplained heritability.Interactions  of  genetic  and  environmental  factors  arethought  to  be  crucial  in  COPD.  So,  we  aim  to  examineinteractions of the endothelial nitric oxide synthase (eNOS)and angiotensin converting enzyme (ACE) genes and ciga-rette smoking in COPD. Methods:The  eNOS  G894T  and  ACE  ID  variants  wereanalyzed  in  122  COPD  patients  and  200  controls  fromSerbia. The effect of the variants on COPD was assessed bylogistic  regression.  Interactions  between  eNOS,  ACE  andcigarette  smoking  in  COPD  were  evaluated  using  a  case-control model. Interaction between the genes was analyzedin silico. Results:No effect of the eNOS G894T and ACE ID variantson  COPD  was  found  in  our  study.  Gene-gene  interactionbetween  the  eNOS  TT  and  ACE  D  was  identified(p=0.033) in COPD. The interaction is realized within the complex network of biochemical pathways. Gene-environ-ment  interactions  between  the  eNOS  T  and  cigarettesmoking (p=0.013), and the ACE II and cigarette smoking(p=0.009) were detected in COPD in our study. Conclusions:This is the first research to reveal interactionsof  the  eNOS  and  ACE  genes  and  cigarette  smoking  inCOPD progressing our understanding of COPD heritabilityand contributing to the development of appropriate treat-ments., Uvod: Hronična opstruktivna bolest pluća (HOBP) je složeno oboljenje sa nerazjašnjenom genetičkom osnovom.Smatra se da su interakcije genetskih i spoljašnjih faktora ključne u HOBP. Stoga je naš cilj bio da ispitamo interakcijegena za endotelijalnu azot-monoksid sintazu (eNOS) i angiotenzin konvertujući enzim (ACE) i duvanskog dima uHOBP. Metode :eNOS G894T i ACE ID varijante su analiziranekod 122 HOBP pacijenta i 200 kontrola iz Srbije. Uticajvarijanti na HOBP je ispitan logističkom regresijom. Interakcije izme|u eNOS, ACE i duvanskog dima u HOBP suispitane korišćenjem modela slučaj-kontrola. Interakciaja između gena je analizirana in silico. Rezultati: Prema ovoj studiji eNOS G894T i ACE ID varijante nemaju uticaj na HOBP. Gen-gen interakcija između eNOS TT i ACE D je identifikovana (p=0,033) u HOBP.Ova interakcija se ostvaruje u okviru složene mreže bio-hemijskih puteva. Gen-sredina interakcije izme|u eNOS Ti duvanskog dima (p=0,013), i ACE II i duvanskog dima(p=0,009) su detektovane u HOBP u ovoj studiji.Zaključak: Ovo je prvo istraživanje u kome su otkriveneinterakcije između eNOS i ACE gena i duvanskog dima uHOBP što doprinosi našem razumevanju genetičke osnove HOBP i razvoju adekvatnog tretmana.",
publisher = "Belgrade : Society of Medical Biochemists of Serbia",
journal = "Journal of Medical Biochemistry",
title = "Interactions of the eNOS and ACE genes and cigarette smoking in chronic obstructive pulmonary disease, Interakcije eNOS i ACE gena i duvanskog dima u hroničnoj opstruktivnoj bolesti pluća",
pages = "104-94",
number = "1",
volume = "41",
doi = "10.5937/jomb0-34017"
}

Stanković, M., Đorđević, V., Tomović, V., Nagorni-Obradović, L., Petrović-Stanojević, N., Kovač, M.,& Radojković, D.. (2023). Interactions of the eNOS and ACE genes and cigarette smoking in chronic obstructive pulmonary disease. in Journal of Medical Biochemistry
Belgrade : Society of Medical Biochemists of Serbia., 41(1), 94-104.
https://doi.org/10.5937/jomb0-34017

Stanković M, Đorđević V, Tomović V, Nagorni-Obradović L, Petrović-Stanojević N, Kovač M, Radojković D. Interactions of the eNOS and ACE genes and cigarette smoking in chronic obstructive pulmonary disease. in Journal of Medical Biochemistry. 2023;41(1):94-104.
doi:10.5937/jomb0-34017 .

Stanković, Marija, Đorđević, Valentina, Tomović, Valentina, Nagorni-Obradović, Ljudmila, Petrović-Stanojević, Nataša, Kovač, Mirjana, Radojković, Dragica, "Interactions of the eNOS and ACE genes and cigarette smoking in chronic obstructive pulmonary disease" in Journal of Medical Biochemistry, 41, no. 1 (2023):94-104,
https://doi.org/10.5937/jomb0-34017 . .

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  - Rakićević, Ljiljana
AU  - Kovač, Mirjana
AU  - Radojković, Dragica
AU  - Radojković, Milica
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1587
AB  - Uvod/Cilj Terapija kumarinima predstavlja jedan od najboljih modela za primenu farmakogenetike. Doprinos faktora koji utiču na terapiju kumarinima može značajno da varira između etničkih grupa, što opravdava sprovođenje studija specifičnih za populaciju. Cilj ove studije je bio da se analizira uticaj najvažnijih genetičkih faktora (geni VKORC1 i CYP2C9) koji utiču na terapiju kumarinima kod bolesnika iz Srbije. Metode Sprovedena je retrospektivna studija koja je obuhvatila 207 bolesnika na terapiji acenokumarolom. Genetičke analize su vršene direktnim sekvenciranjem. Analiziran je uticaj na dozu acenokumarola varijanti (VKORC1*2, CYP2C9*2, CYP2C9*3) koje izazivaju preosetljivost i varijanti gena VKORC1 koje izazivaju rezistenciju na kumarine. Višestruka regresiona analiza je korišćena u cilju dizajniranja matematičkog modela za predviđanje individualne doze leka na osnovu kliničko-demografskih i genetičkih podataka. Rezultati Studija je potvrdila značajan uticaj analiziranih genetičkih faktora na održavanje doze acenokumarola. Dizajniran je matematički model za predviđanje individualne doze acenokumarola i njegov nekorigovani R2 je bio 61,8. Prilikom testiranja, naš model je dao R2 vrednost od 42,6 i pokazao bolje predviđanje u poređenju sa modelom koji su dali drugi autori. Kod analiziranih bolesnika pronađeno je devet različitih varijanti u kodirajućem regionu gena VKORC1. Među nosiocima ovih varijanti 78% je bilo potpuno rezistentno, te nije bilo moguće postići terapeutski efekat čak ni sa visokim dozama acenokumarola. Zaključci Populacioni model za predviđanje individualne doze acenokumarola može pokazati prednosti u odnosu na modele koji se koriste na generalizovan način. Takođe, VKORC1 varijante koje izazivaju rezistenciju na kumarin treba uzeti u obzir prilikom planiranja terapije.
AB  - Introduction/Objective Coumarin therapy represents one of the best models for applying pharmacogenetics. The contribution of factors influencing coumarin therapy can vary significantly between ethnic groups, which justifies conducting population-specific studies. The aim of this study was to analyze the influence of the most important genetic factors (VKORC1 and CYP2C9 genes) that affect coumarin therapy in patients from Serbia. Methods A retrospective study involving 207 patients on acenocoumarol therapy was conducted. Genetic analyses were performed by direct sequencing. Influence on acenocoumarol dose of variants (VKORC1, CYP2C9*2, CYP2C9*3) causing hypersensitivity and VKORC1 variants causing resistance to acenocoumarol were analyzed. Multiple regression analysis was used to design a mathematical model for predicting individual drug dosage based on clinical-demographic and genetic data. Results The study confirmed significant influence of the analyzed genetic factors on acenocoumarol maintenance dose. We designed mathematical model for predicting individual acenocoumarol dose and its unadjusted R2 was 61.8. In the testing cohort, our model gave R2 value of 42.6 and showed better prediction in comparison with model given by other authors. In the analyzed patients, nine different variants in the VKORC1 coding region were found. Among carriers of these variants 78% were completely resistant, and it was not possible to achieve therapeutic effect even with high doses of acenocoumarol. Conclusions Population-specific model for prediction individual dose of acenocoumarol, may show advantages over protocols that are used in a generalized manner. Also, VKORC1 variants which cause coumarin resistance should be considered when planning therapy.
PB  - Srpsko lekarsko društvo, Beograd
T2  - Srpski arhiv za celokupno lekarstvo
T1  - Varijante gena "VKORC1" i "CYP2C9" kao farmakogenetički faktori u terapiji acenokumarolom kod bolesnika u Srbiji - razmatranje preosetljivosti i rezistencije
T1  - The 'VKORC1' and 'CYP2C9' gene variants as pharmacogenetic factors in acenocoumarol therapy in Serbian patients: Consideration of hypersensitivity and resistance
EP  - 162
IS  - 3-4
SP  - 156
VL  - 150
DO  - 10.2298/SARH211118013R
ER  - 

@article{
author = "Rakićević, Ljiljana and Kovač, Mirjana and Radojković, Dragica and Radojković, Milica",
year = "2022",
abstract = "Uvod/Cilj Terapija kumarinima predstavlja jedan od najboljih modela za primenu farmakogenetike. Doprinos faktora koji utiču na terapiju kumarinima može značajno da varira između etničkih grupa, što opravdava sprovođenje studija specifičnih za populaciju. Cilj ove studije je bio da se analizira uticaj najvažnijih genetičkih faktora (geni VKORC1 i CYP2C9) koji utiču na terapiju kumarinima kod bolesnika iz Srbije. Metode Sprovedena je retrospektivna studija koja je obuhvatila 207 bolesnika na terapiji acenokumarolom. Genetičke analize su vršene direktnim sekvenciranjem. Analiziran je uticaj na dozu acenokumarola varijanti (VKORC1*2, CYP2C9*2, CYP2C9*3) koje izazivaju preosetljivost i varijanti gena VKORC1 koje izazivaju rezistenciju na kumarine. Višestruka regresiona analiza je korišćena u cilju dizajniranja matematičkog modela za predviđanje individualne doze leka na osnovu kliničko-demografskih i genetičkih podataka. Rezultati Studija je potvrdila značajan uticaj analiziranih genetičkih faktora na održavanje doze acenokumarola. Dizajniran je matematički model za predviđanje individualne doze acenokumarola i njegov nekorigovani R2 je bio 61,8. Prilikom testiranja, naš model je dao R2 vrednost od 42,6 i pokazao bolje predviđanje u poređenju sa modelom koji su dali drugi autori. Kod analiziranih bolesnika pronađeno je devet različitih varijanti u kodirajućem regionu gena VKORC1. Među nosiocima ovih varijanti 78% je bilo potpuno rezistentno, te nije bilo moguće postići terapeutski efekat čak ni sa visokim dozama acenokumarola. Zaključci Populacioni model za predviđanje individualne doze acenokumarola može pokazati prednosti u odnosu na modele koji se koriste na generalizovan način. Takođe, VKORC1 varijante koje izazivaju rezistenciju na kumarin treba uzeti u obzir prilikom planiranja terapije., Introduction/Objective Coumarin therapy represents one of the best models for applying pharmacogenetics. The contribution of factors influencing coumarin therapy can vary significantly between ethnic groups, which justifies conducting population-specific studies. The aim of this study was to analyze the influence of the most important genetic factors (VKORC1 and CYP2C9 genes) that affect coumarin therapy in patients from Serbia. Methods A retrospective study involving 207 patients on acenocoumarol therapy was conducted. Genetic analyses were performed by direct sequencing. Influence on acenocoumarol dose of variants (VKORC1, CYP2C9*2, CYP2C9*3) causing hypersensitivity and VKORC1 variants causing resistance to acenocoumarol were analyzed. Multiple regression analysis was used to design a mathematical model for predicting individual drug dosage based on clinical-demographic and genetic data. Results The study confirmed significant influence of the analyzed genetic factors on acenocoumarol maintenance dose. We designed mathematical model for predicting individual acenocoumarol dose and its unadjusted R2 was 61.8. In the testing cohort, our model gave R2 value of 42.6 and showed better prediction in comparison with model given by other authors. In the analyzed patients, nine different variants in the VKORC1 coding region were found. Among carriers of these variants 78% were completely resistant, and it was not possible to achieve therapeutic effect even with high doses of acenocoumarol. Conclusions Population-specific model for prediction individual dose of acenocoumarol, may show advantages over protocols that are used in a generalized manner. Also, VKORC1 variants which cause coumarin resistance should be considered when planning therapy.",
publisher = "Srpsko lekarsko društvo, Beograd",
journal = "Srpski arhiv za celokupno lekarstvo",
title = "Varijante gena "VKORC1" i "CYP2C9" kao farmakogenetički faktori u terapiji acenokumarolom kod bolesnika u Srbiji - razmatranje preosetljivosti i rezistencije, The 'VKORC1' and 'CYP2C9' gene variants as pharmacogenetic factors in acenocoumarol therapy in Serbian patients: Consideration of hypersensitivity and resistance",
pages = "162-156",
number = "3-4",
volume = "150",
doi = "10.2298/SARH211118013R"
}

Rakićević, L., Kovač, M., Radojković, D.,& Radojković, M.. (2022). Varijante gena "VKORC1" i "CYP2C9" kao farmakogenetički faktori u terapiji acenokumarolom kod bolesnika u Srbiji - razmatranje preosetljivosti i rezistencije. in Srpski arhiv za celokupno lekarstvo
Srpsko lekarsko društvo, Beograd., 150(3-4), 156-162.
https://doi.org/10.2298/SARH211118013R

Rakićević L, Kovač M, Radojković D, Radojković M. Varijante gena "VKORC1" i "CYP2C9" kao farmakogenetički faktori u terapiji acenokumarolom kod bolesnika u Srbiji - razmatranje preosetljivosti i rezistencije. in Srpski arhiv za celokupno lekarstvo. 2022;150(3-4):156-162.
doi:10.2298/SARH211118013R .

Rakićević, Ljiljana, Kovač, Mirjana, Radojković, Dragica, Radojković, Milica, "Varijante gena "VKORC1" i "CYP2C9" kao farmakogenetički faktori u terapiji acenokumarolom kod bolesnika u Srbiji - razmatranje preosetljivosti i rezistencije" in Srpski arhiv za celokupno lekarstvo, 150, no. 3-4 (2022):156-162,
https://doi.org/10.2298/SARH211118013R . .

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

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

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

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

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

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

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

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

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

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

TY  - CONF
AU  - Bačković, Dragana
AU  - Novković, Mirjana
AU  - Matić, Dragan
AU  - Antonijević, Nebojša
AU  - Strugarević, Evgenija
AU  - Kovač, Mirjana
AU  - Kušić-Tišma, Jelena
AU  - Rakićević, Ljiljana
AU  - Radojković, Dragica
PY  - 2021
UR  - https://www.uksrb.rs/en/magazine/archive/heart-and-blood-vessels-number-32021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2344
AB  - Introduction. Despite proven clinical effect of clopidogrel, a
considerable number of patients do not have an adequate
response to this type of medication. Problems during therapy occur in the form of resistance, which is present in 11%
of patients or bleeding that occurs in about 9% of patients.
Pharmacogenomics studies demonstrated that variants of
the CYP2C19 gene significantly influence the interindividual heterogenity of the clopidogrel response. The American
Heart Association, US Food and Drug Administration and the
European Medicines Agency, cite the CYP2C19 gene as a significant factor which influences patients response to clopidogrel. Further, it has been shown that the contribution of
genetic and non-genetic factors affecting clopidogrel therapy
may vary between patients from different populations, which
justifies conducting population-specific studies.
The aim. The aim of our study was to examine the significance
of the CYP2C19*2 and the CYP2C19*17 variants in the individual response to clopidogrel, in Serbian patients.
Methods. The study involved 108 patients with carotid artery
stenosis who underwent endarterectomy and received clopidogrel for at least 30 days after the intervention. Also, 120
patients with myocardial infarction receiving clopidogrel after PCI (percutaneous coronary intervention) were included.
Commercial tests were used for standard laboratory testing.
Allelic discrimination was performed after Sanger sequencing.
Results were analysed using statistical tests.
Results. In patients undergoing endarterectomy CYP2C19*2
carriers had a higher risk for being clopidogrel low-responder
in comparison with non-carriers (1.250, 95% CI 1.695–1.658,
P<0.01). In the group of patients undergoing PCI, risk for reinfarction in patients who were carriers of CYP2C19*2 was higher
compared to patients with wild type genotype (OR 5.355, 95%
CI 0.955-31.08; P=0.038). Variant CYP2C19*17 showed no association with variations in response to clopidogrel therapy.
Conclusion. The CYP2C19*2 variant shows significant association with a poor response to clopidogrel and it should be
considered when planning therapy.
PB  - Beograd : Udruženje kardiologa Srbije
C3  - Heart and Blood Vessels
T1  - Analysis of the association of the CYP2C19 variants with the effects of clopidogrel therapy in patients underwent to carotid endarterectomy
IS  - 3
VL  - 40
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2344
ER  - 

@conference{
author = "Bačković, Dragana and Novković, Mirjana and Matić, Dragan and Antonijević, Nebojša and Strugarević, Evgenija and Kovač, Mirjana and Kušić-Tišma, Jelena and Rakićević, Ljiljana and Radojković, Dragica",
year = "2021",
abstract = "Introduction. Despite proven clinical effect of clopidogrel, a
considerable number of patients do not have an adequate
response to this type of medication. Problems during therapy occur in the form of resistance, which is present in 11%
of patients or bleeding that occurs in about 9% of patients.
Pharmacogenomics studies demonstrated that variants of
the CYP2C19 gene significantly influence the interindividual heterogenity of the clopidogrel response. The American
Heart Association, US Food and Drug Administration and the
European Medicines Agency, cite the CYP2C19 gene as a significant factor which influences patients response to clopidogrel. Further, it has been shown that the contribution of
genetic and non-genetic factors affecting clopidogrel therapy
may vary between patients from different populations, which
justifies conducting population-specific studies.
The aim. The aim of our study was to examine the significance
of the CYP2C19*2 and the CYP2C19*17 variants in the individual response to clopidogrel, in Serbian patients.
Methods. The study involved 108 patients with carotid artery
stenosis who underwent endarterectomy and received clopidogrel for at least 30 days after the intervention. Also, 120
patients with myocardial infarction receiving clopidogrel after PCI (percutaneous coronary intervention) were included.
Commercial tests were used for standard laboratory testing.
Allelic discrimination was performed after Sanger sequencing.
Results were analysed using statistical tests.
Results. In patients undergoing endarterectomy CYP2C19*2
carriers had a higher risk for being clopidogrel low-responder
in comparison with non-carriers (1.250, 95% CI 1.695–1.658,
P<0.01). In the group of patients undergoing PCI, risk for reinfarction in patients who were carriers of CYP2C19*2 was higher
compared to patients with wild type genotype (OR 5.355, 95%
CI 0.955-31.08; P=0.038). Variant CYP2C19*17 showed no association with variations in response to clopidogrel therapy.
Conclusion. The CYP2C19*2 variant shows significant association with a poor response to clopidogrel and it should be
considered when planning therapy.",
publisher = "Beograd : Udruženje kardiologa Srbije",
journal = "Heart and Blood Vessels",
title = "Analysis of the association of the CYP2C19 variants with the effects of clopidogrel therapy in patients underwent to carotid endarterectomy",
number = "3",
volume = "40",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2344"
}

Bačković, D., Novković, M., Matić, D., Antonijević, N., Strugarević, E., Kovač, M., Kušić-Tišma, J., Rakićević, L.,& Radojković, D.. (2021). Analysis of the association of the CYP2C19 variants with the effects of clopidogrel therapy in patients underwent to carotid endarterectomy. in Heart and Blood Vessels
Beograd : Udruženje kardiologa Srbije., 40(3).
https://hdl.handle.net/21.15107/rcub_imagine_2344

Bačković D, Novković M, Matić D, Antonijević N, Strugarević E, Kovač M, Kušić-Tišma J, Rakićević L, Radojković D. Analysis of the association of the CYP2C19 variants with the effects of clopidogrel therapy in patients underwent to carotid endarterectomy. in Heart and Blood Vessels. 2021;40(3).
https://hdl.handle.net/21.15107/rcub_imagine_2344 .

Bačković, Dragana, Novković, Mirjana, Matić, Dragan, Antonijević, Nebojša, Strugarević, Evgenija, Kovač, Mirjana, Kušić-Tišma, Jelena, Rakićević, Ljiljana, Radojković, Dragica, "Analysis of the association of the CYP2C19 variants with the effects of clopidogrel therapy in patients underwent to carotid endarterectomy" in Heart and Blood Vessels, 40, no. 3 (2021),
https://hdl.handle.net/21.15107/rcub_imagine_2344 .

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

TY  - JOUR
AU  - Kovač, Mirjana
AU  - Mitić, Gorana
AU  - Lalić-Cosić, Sanja
AU  - Đorđević, Valentina
AU  - Tomić, Branko
AU  - Muszbek, Laszlo
AU  - Bereczky, Zsuzsanna
PY  - 2018
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1108
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Thrombosis Research
T1  - Evaluation of endogenous thrombin potential among patients with antithrombin deficiency
EP  - 53
SP  - 50
VL  - 166
DO  - 10.1016/j.thromres.2018.04.004
ER  - 

@article{
author = "Kovač, Mirjana and Mitić, Gorana and Lalić-Cosić, Sanja and Đorđević, Valentina and Tomić, Branko and Muszbek, Laszlo and Bereczky, Zsuzsanna",
year = "2018",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Thrombosis Research",
title = "Evaluation of endogenous thrombin potential among patients with antithrombin deficiency",
pages = "53-50",
volume = "166",
doi = "10.1016/j.thromres.2018.04.004"
}

Kovač, M., Mitić, G., Lalić-Cosić, S., Đorđević, V., Tomić, B., Muszbek, L.,& Bereczky, Z.. (2018). Evaluation of endogenous thrombin potential among patients with antithrombin deficiency. in Thrombosis Research
Pergamon-Elsevier Science Ltd, Oxford., 166, 50-53.
https://doi.org/10.1016/j.thromres.2018.04.004

Kovač M, Mitić G, Lalić-Cosić S, Đorđević V, Tomić B, Muszbek L, Bereczky Z. Evaluation of endogenous thrombin potential among patients with antithrombin deficiency. in Thrombosis Research. 2018;166:50-53.
doi:10.1016/j.thromres.2018.04.004 .

Kovač, Mirjana, Mitić, Gorana, Lalić-Cosić, Sanja, Đorđević, Valentina, Tomić, Branko, Muszbek, Laszlo, Bereczky, Zsuzsanna, "Evaluation of endogenous thrombin potential among patients with antithrombin deficiency" in Thrombosis Research, 166 (2018):50-53,
https://doi.org/10.1016/j.thromres.2018.04.004 . .

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  - 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  - Kovač, Mirjana
AU  - Mitić, Gorana
AU  - Jesić, Milos
AU  - Đorđević, Valentina
AU  - Muszbek, Laszlo
AU  - Bereczky, Zsuzsanna
PY  - 2017
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1072
AB  - The overall incidence of thromboembolic events in the neonatal period is 5 per 100 000 births, wherein more than 40% of all such manifestations are symptomatic renal vein thromboses. We describe the case of a newborn female who developed extensive thrombosis, which filled the inferior vena cava and renal vein and was diagnosed in the first weeks of life. A homozygous type II heparin-binding site antithrombin deficiency (c.391C gt T, p.Leu131Phe) was detected in the background. Despite the timely diagnosis and appropriate treatment, clinical signs of renal insufficiency, because of left kidney atrophy and arterial hypertension, were observed. Our case demonstrates the seriousness of the consequences arising after early onset of venous thrombosis caused by homozygous type II heparin-binding site antithrombin deficiency. In addition to prompt diagnosis, of huge importance is the determination of inherited thrombophilia, as it significantly affects therapeutic treatment and indicates that long-term follow-up is mandatory.
PB  - Lippincott Williams & Wilkins, Philadelphia
T2  - Blood Coagulation & Fibrinolysis
T1  - Early onset of abdominal venous thrombosis in a newborn with homozygous type II heparin-binding site antithrombin deficiency
EP  - 266
IS  - 3
SP  - 264
VL  - 28
DO  - 10.1097/MBC.0000000000000570
ER  - 

@article{
author = "Kovač, Mirjana and Mitić, Gorana and Jesić, Milos and Đorđević, Valentina and Muszbek, Laszlo and Bereczky, Zsuzsanna",
year = "2017",
abstract = "The overall incidence of thromboembolic events in the neonatal period is 5 per 100 000 births, wherein more than 40% of all such manifestations are symptomatic renal vein thromboses. We describe the case of a newborn female who developed extensive thrombosis, which filled the inferior vena cava and renal vein and was diagnosed in the first weeks of life. A homozygous type II heparin-binding site antithrombin deficiency (c.391C gt T, p.Leu131Phe) was detected in the background. Despite the timely diagnosis and appropriate treatment, clinical signs of renal insufficiency, because of left kidney atrophy and arterial hypertension, were observed. Our case demonstrates the seriousness of the consequences arising after early onset of venous thrombosis caused by homozygous type II heparin-binding site antithrombin deficiency. In addition to prompt diagnosis, of huge importance is the determination of inherited thrombophilia, as it significantly affects therapeutic treatment and indicates that long-term follow-up is mandatory.",
publisher = "Lippincott Williams & Wilkins, Philadelphia",
journal = "Blood Coagulation & Fibrinolysis",
title = "Early onset of abdominal venous thrombosis in a newborn with homozygous type II heparin-binding site antithrombin deficiency",
pages = "266-264",
number = "3",
volume = "28",
doi = "10.1097/MBC.0000000000000570"
}

Kovač, M., Mitić, G., Jesić, M., Đorđević, V., Muszbek, L.,& Bereczky, Z.. (2017). Early onset of abdominal venous thrombosis in a newborn with homozygous type II heparin-binding site antithrombin deficiency. in Blood Coagulation & Fibrinolysis
Lippincott Williams & Wilkins, Philadelphia., 28(3), 264-266.
https://doi.org/10.1097/MBC.0000000000000570

Kovač M, Mitić G, Jesić M, Đorđević V, Muszbek L, Bereczky Z. Early onset of abdominal venous thrombosis in a newborn with homozygous type II heparin-binding site antithrombin deficiency. in Blood Coagulation & Fibrinolysis. 2017;28(3):264-266.
doi:10.1097/MBC.0000000000000570 .

Kovač, Mirjana, Mitić, Gorana, Jesić, Milos, Đorđević, Valentina, Muszbek, Laszlo, Bereczky, Zsuzsanna, "Early onset of abdominal venous thrombosis in a newborn with homozygous type II heparin-binding site antithrombin deficiency" in Blood Coagulation & Fibrinolysis, 28, no. 3 (2017):264-266,
https://doi.org/10.1097/MBC.0000000000000570 . .

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  - JOUR
AU  - Kovač, Mirjana
AU  - Mitić, Gorana
AU  - Miković, Zeljko
AU  - Mandić, Vesna
AU  - Đorđević, Valentina
AU  - Muszbek, Laszlo
AU  - Bereczky, Zsuzsanna
PY  - 2016
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/990
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Thrombosis Research
T1  - Pregnancy related stroke in the setting of homozygous type-II HBS antithrombin deficiency
EP  - 113
SP  - 111
VL  - 139
DO  - 10.1016/j.thromres.2016.01.018
ER  - 

@article{
author = "Kovač, Mirjana and Mitić, Gorana and Miković, Zeljko and Mandić, Vesna and Đorđević, Valentina and Muszbek, Laszlo and Bereczky, Zsuzsanna",
year = "2016",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Thrombosis Research",
title = "Pregnancy related stroke in the setting of homozygous type-II HBS antithrombin deficiency",
pages = "113-111",
volume = "139",
doi = "10.1016/j.thromres.2016.01.018"
}

Kovač, M., Mitić, G., Miković, Z., Mandić, V., Đorđević, V., Muszbek, L.,& Bereczky, Z.. (2016). Pregnancy related stroke in the setting of homozygous type-II HBS antithrombin deficiency. in Thrombosis Research
Pergamon-Elsevier Science Ltd, Oxford., 139, 111-113.
https://doi.org/10.1016/j.thromres.2016.01.018

Kovač M, Mitić G, Miković Z, Mandić V, Đorđević V, Muszbek L, Bereczky Z. Pregnancy related stroke in the setting of homozygous type-II HBS antithrombin deficiency. in Thrombosis Research. 2016;139:111-113.
doi:10.1016/j.thromres.2016.01.018 .

Kovač, Mirjana, Mitić, Gorana, Miković, Zeljko, Mandić, Vesna, Đorđević, Valentina, Muszbek, Laszlo, Bereczky, Zsuzsanna, "Pregnancy related stroke in the setting of homozygous type-II HBS antithrombin deficiency" in Thrombosis Research, 139 (2016):111-113,
https://doi.org/10.1016/j.thromres.2016.01.018 . .

TY  - JOUR
AU  - Bačković, Dragana
AU  - Ignjatović, Svetlana
AU  - Rakićević, Ljiljana
AU  - Kušić-Tišma, Jelena
AU  - Radojković, Dragica
AU  - Ćalija, Branko
AU  - Strugarević, Evgenija
AU  - Radak, Đorđe
AU  - Kovač, Mirjana
PY  - 2016
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/988
AB  - Uvod: I pored dokazanog kliničkog efekta oralne antiagregacijske terapije, značajan broj pacijenata nema adekvatan odgovor na primenjeni klopidogrel. Cilj naše studije je bio da se utvrdi uticaj prisutne CYP2C19*2 varijante gena na terapijski odgovor u toku primene klopidogrela kod pacijenata sa stenozom karotidne arterije. Metode: U jednogodišnju prospektivnu studiju uključeno je 112 pacijenata sa stenozom karotidne arterije kod kojih je izvršena endarterektomija. Posle operativnog zahvata, pacijenti su primali 75 mg dnevno klopidogrela u trajanju od najmanje mesec dana. Svi ispitanici su praćeni od momenta prijema. Za CYP2C19 genotipizaciju korišćen je TaqMan test. Uticaj CYP2C19*2 alela na trombocitnu reaktivnost ispitivan je primenom multiple-electrode aggregometry (MEA). Rezultati: Rezultati genotipizacije su pokazali da su 82 (73,2%) ispitanika homozigoti za wild-type, 29 (25,9%) heterozigoti za CYP2C19*2 alel, dok je 1 (0,9%) bio homozigot za CYP2C19*2. Nakon 24 sata, u grupi sa wild-type genotipom 29,3% ispitanika dali su odgovor na klopidogrel, a u grupi sa CYP2C19*2 varijantom gena 10% ispitanika. U grupi sa wild-type genotipom, 74,4% ispitanika su imali terapijski odgovor nakon 7 dana, odnosno 82,9% nakon 30 dana od primene klopidogrela. U grupi sa CYP2C19*2 alelom broj ispitanika sa terapijskim odgovorom raste do 46,7% nakon 7 dana, odnosno do 53,3% nakon 30 dana od primene klopidogrela. Rizik za slab odgovor je veći kod nosilaca CYP2C19*2 alela u odnosu na nenosioce (wild-type) (OR 4,250, 95% CI 1 .695 -10.658 , P lt  0,01). Zaključak: CYP2C19*2 varijanta gena značajno utiče na terapijski odgovor u toku primene klopidogrela kod bolesnika sa stenozom karotidne arterije kod kojih je izvršena endarterektomija.
AB  - Background: Despite the proven clinical effect of oral antiplatelet drugs, a considerable number of patients do not have an adequate response to clopidogrel. The aim of our study was to determine the influence of CYP2C19*2 loss-of-function variant allele on clopidogrel responsiveness in patients with carotid artery stenosis. Methods: One hundred and twelve patients with carotid artery stenosis undergoing endarterectomy were included in this one-year prospective study. All of them received clopidogrel (75 mg daily) for at least 30 days after the intervention. They were followed from the moment of hospital admission. CYP2C19*2 genotyping was performed by TaqMan Assay. The influence of c Yp 2C 19*2 variant allele on clopidogrel platelet reactivity was determined using multiple-electrode aggregometry (MEA). Results: Genotyping results showed that 82 (73.2% ) patients were homozygous for wild type, 29 (25.9%) were heterozygous for the CYP2C19*2 allele and 1 (0.9%) was CYP2C19*2 homozygous. After 24 hours, among those with the wild type 29.3% were clopidogrel responders, and in those with the CYP2C19*2 alleles 10%. In the wild type group, 74.4% were clopidogrel responders after 7 days of taking the drug; 82.9% after 30 days of clopidogrel introduction, respectively. In patients with the CYP2C19*2 alleles the number of responders increased up to 46.7% after 7 days; 53.3% after 30 days of taking the drug, respectively. The risk for being a low-responder is higher for the patients heterozygous for the c Yp 2C 19*2 allele vs. wildtype (OR 4.250, 95% CI 1.695 -10.658 , P lt  0.01). Conclusions: The CYP2C19*2 loss-of-function variant allele has significant influence on clopidogrel response in patients with carotid artery stenosis undergoing endarterectomy.
PB  - Društvo medicinskih biohemičara Srbije, Beograd i Versita
T2  - Journal of Medical Biochemistry
T1  - Uticaj CYP2C19*2 varijante gena na terapijski odgovor u toku primene klopidogrela kod bolesnika sa stenozom karotidne arterije
T1  - Influence of CYP2C19*2 gene variant on therapeutic response during clopidogrel treatment in patients with carotid artery stenosis
EP  - 33
IS  - 1
SP  - 26
VL  - 35
DO  - 10.1515/jomb-2015-0009
ER  - 

@article{
author = "Bačković, Dragana and Ignjatović, Svetlana and Rakićević, Ljiljana and Kušić-Tišma, Jelena and Radojković, Dragica and Ćalija, Branko and Strugarević, Evgenija and Radak, Đorđe and Kovač, Mirjana",
year = "2016",
abstract = "Uvod: I pored dokazanog kliničkog efekta oralne antiagregacijske terapije, značajan broj pacijenata nema adekvatan odgovor na primenjeni klopidogrel. Cilj naše studije je bio da se utvrdi uticaj prisutne CYP2C19*2 varijante gena na terapijski odgovor u toku primene klopidogrela kod pacijenata sa stenozom karotidne arterije. Metode: U jednogodišnju prospektivnu studiju uključeno je 112 pacijenata sa stenozom karotidne arterije kod kojih je izvršena endarterektomija. Posle operativnog zahvata, pacijenti su primali 75 mg dnevno klopidogrela u trajanju od najmanje mesec dana. Svi ispitanici su praćeni od momenta prijema. Za CYP2C19 genotipizaciju korišćen je TaqMan test. Uticaj CYP2C19*2 alela na trombocitnu reaktivnost ispitivan je primenom multiple-electrode aggregometry (MEA). Rezultati: Rezultati genotipizacije su pokazali da su 82 (73,2%) ispitanika homozigoti za wild-type, 29 (25,9%) heterozigoti za CYP2C19*2 alel, dok je 1 (0,9%) bio homozigot za CYP2C19*2. Nakon 24 sata, u grupi sa wild-type genotipom 29,3% ispitanika dali su odgovor na klopidogrel, a u grupi sa CYP2C19*2 varijantom gena 10% ispitanika. U grupi sa wild-type genotipom, 74,4% ispitanika su imali terapijski odgovor nakon 7 dana, odnosno 82,9% nakon 30 dana od primene klopidogrela. U grupi sa CYP2C19*2 alelom broj ispitanika sa terapijskim odgovorom raste do 46,7% nakon 7 dana, odnosno do 53,3% nakon 30 dana od primene klopidogrela. Rizik za slab odgovor je veći kod nosilaca CYP2C19*2 alela u odnosu na nenosioce (wild-type) (OR 4,250, 95% CI 1 .695 -10.658 , P lt  0,01). Zaključak: CYP2C19*2 varijanta gena značajno utiče na terapijski odgovor u toku primene klopidogrela kod bolesnika sa stenozom karotidne arterije kod kojih je izvršena endarterektomija., Background: Despite the proven clinical effect of oral antiplatelet drugs, a considerable number of patients do not have an adequate response to clopidogrel. The aim of our study was to determine the influence of CYP2C19*2 loss-of-function variant allele on clopidogrel responsiveness in patients with carotid artery stenosis. Methods: One hundred and twelve patients with carotid artery stenosis undergoing endarterectomy were included in this one-year prospective study. All of them received clopidogrel (75 mg daily) for at least 30 days after the intervention. They were followed from the moment of hospital admission. CYP2C19*2 genotyping was performed by TaqMan Assay. The influence of c Yp 2C 19*2 variant allele on clopidogrel platelet reactivity was determined using multiple-electrode aggregometry (MEA). Results: Genotyping results showed that 82 (73.2% ) patients were homozygous for wild type, 29 (25.9%) were heterozygous for the CYP2C19*2 allele and 1 (0.9%) was CYP2C19*2 homozygous. After 24 hours, among those with the wild type 29.3% were clopidogrel responders, and in those with the CYP2C19*2 alleles 10%. In the wild type group, 74.4% were clopidogrel responders after 7 days of taking the drug; 82.9% after 30 days of clopidogrel introduction, respectively. In patients with the CYP2C19*2 alleles the number of responders increased up to 46.7% after 7 days; 53.3% after 30 days of taking the drug, respectively. The risk for being a low-responder is higher for the patients heterozygous for the c Yp 2C 19*2 allele vs. wildtype (OR 4.250, 95% CI 1.695 -10.658 , P lt  0.01). Conclusions: The CYP2C19*2 loss-of-function variant allele has significant influence on clopidogrel response in patients with carotid artery stenosis undergoing endarterectomy.",
publisher = "Društvo medicinskih biohemičara Srbije, Beograd i Versita",
journal = "Journal of Medical Biochemistry",
title = "Uticaj CYP2C19*2 varijante gena na terapijski odgovor u toku primene klopidogrela kod bolesnika sa stenozom karotidne arterije, Influence of CYP2C19*2 gene variant on therapeutic response during clopidogrel treatment in patients with carotid artery stenosis",
pages = "33-26",
number = "1",
volume = "35",
doi = "10.1515/jomb-2015-0009"
}

Bačković, D., Ignjatović, S., Rakićević, L., Kušić-Tišma, J., Radojković, D., Ćalija, B., Strugarević, E., Radak, Đ.,& Kovač, M.. (2016). Uticaj CYP2C19*2 varijante gena na terapijski odgovor u toku primene klopidogrela kod bolesnika sa stenozom karotidne arterije. in Journal of Medical Biochemistry
Društvo medicinskih biohemičara Srbije, Beograd i Versita., 35(1), 26-33.
https://doi.org/10.1515/jomb-2015-0009

Bačković D, Ignjatović S, Rakićević L, Kušić-Tišma J, Radojković D, Ćalija B, Strugarević E, Radak Đ, Kovač M. Uticaj CYP2C19*2 varijante gena na terapijski odgovor u toku primene klopidogrela kod bolesnika sa stenozom karotidne arterije. in Journal of Medical Biochemistry. 2016;35(1):26-33.
doi:10.1515/jomb-2015-0009 .

Bačković, Dragana, Ignjatović, Svetlana, Rakićević, Ljiljana, Kušić-Tišma, Jelena, Radojković, Dragica, Ćalija, Branko, Strugarević, Evgenija, Radak, Đorđe, Kovač, Mirjana, "Uticaj CYP2C19*2 varijante gena na terapijski odgovor u toku primene klopidogrela kod bolesnika sa stenozom karotidne arterije" in Journal of Medical Biochemistry, 35, no. 1 (2016):26-33,
https://doi.org/10.1515/jomb-2015-0009 . .

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  - 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  - CONF
AU  - Backović, D.
AU  - Ignjatović, S.
AU  - Rakićević, Ljiljana
AU  - Novković, Mirjana
AU  - Kušić-Tišma, Jelena
AU  - Radojković, Dragica
AU  - Strugarević, E.
AU  - Calija, B.
AU  - Radak, D.
AU  - Kovač, Mirjana
PY  - 2016
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/940
PB  - Wiley-Blackwell, Hoboken
C3  - Journal of Thrombosis and Haemostasis
T1  - Risk factors for clopidogrel high on-treatment platelet reactivity in patients with carotid artery stenosis undergoing endarterectomy
EP  - 110
SP  - 110
VL  - 14
UR  - https://hdl.handle.net/21.15107/rcub_imagine_940
ER  - 

@conference{
author = "Backović, D. and Ignjatović, S. and Rakićević, Ljiljana and Novković, Mirjana and Kušić-Tišma, Jelena and Radojković, Dragica and Strugarević, E. and Calija, B. and Radak, D. and Kovač, Mirjana",
year = "2016",
publisher = "Wiley-Blackwell, Hoboken",
journal = "Journal of Thrombosis and Haemostasis",
title = "Risk factors for clopidogrel high on-treatment platelet reactivity in patients with carotid artery stenosis undergoing endarterectomy",
pages = "110-110",
volume = "14",
url = "https://hdl.handle.net/21.15107/rcub_imagine_940"
}

Backović, D., Ignjatović, S., Rakićević, L., Novković, M., Kušić-Tišma, J., Radojković, D., Strugarević, E., Calija, B., Radak, D.,& Kovač, M.. (2016). Risk factors for clopidogrel high on-treatment platelet reactivity in patients with carotid artery stenosis undergoing endarterectomy. in Journal of Thrombosis and Haemostasis
Wiley-Blackwell, Hoboken., 14, 110-110.
https://hdl.handle.net/21.15107/rcub_imagine_940

Backović D, Ignjatović S, Rakićević L, Novković M, Kušić-Tišma J, Radojković D, Strugarević E, Calija B, Radak D, Kovač M. Risk factors for clopidogrel high on-treatment platelet reactivity in patients with carotid artery stenosis undergoing endarterectomy. in Journal of Thrombosis and Haemostasis. 2016;14:110-110.
https://hdl.handle.net/21.15107/rcub_imagine_940 .

Backović, D., Ignjatović, S., Rakićević, Ljiljana, Novković, Mirjana, Kušić-Tišma, Jelena, Radojković, Dragica, Strugarević, E., Calija, B., Radak, D., Kovač, Mirjana, "Risk factors for clopidogrel high on-treatment platelet reactivity in patients with carotid artery stenosis undergoing endarterectomy" in Journal of Thrombosis and Haemostasis, 14 (2016):110-110,
https://hdl.handle.net/21.15107/rcub_imagine_940 .