Backović, Dragana

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  • Backović, Dragana (3)
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Influence of DOACS and DOAC-REMOVE® on coagulation assays during thrombophilia testing in DOAC-treated patients

Kovač, Mirjana; Basarić, Dušica; Tomić, Branko; Gvozdenov, Maja; Backović, Dragana; Lalić-Ćosić, Sanja

(Inst. Sci. inf., Univ. Defence in Belgrade, 2022)

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://farfar.pharmacy.bg.ac.rs/handle/123456789/4437
AB  - Background/Aim. 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  - Uvod/Cilj. 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) na
testove koagulacije tokom ispitivanja trombofilije. Metode.
Istraživanjem, sprovedenim od januara 2019. do juna 2020.
godine, obuhvaćeno je 30 bolesnika lečenih DOAK-om i
testiranih na trombofiliju zbog venskog tromboembolzma
(VTE). Bilo je 14 žena i 16 muškaraca, starosti od 23 do 63
godine (medijana 47,6 godina). Ispitivanje trombofilije izvršeno
je upotrebom DOAC-Remove® tableta (aktivni ugalj).
Upoređivani su rezultati pre i posle primene DOAC-Remove®.
Rezultati. Pozitivni rezultati za lupus antikoagulantni (LA) test
dobijeni su kod 20% bolesnika lečenih apiksabanom, kod
100% bolesnika lečenih dabigatranom i kod 70% lečenih riva-
roksabanom, a u uzorcima posle DOAC-Remove® pozitivnost
na LA dobijena je samo kod jednog bolesnika iz grupe lečnih
apiksabanom. Pre primene DOAC-Remove®, rezistencija na
aktivisani protein C (activated protein C resistance – APC-R) bila je
merljiva 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 posle
primene DOAC-Remove®, primećena je razlika u odnosu na
sve 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. Nakon
primene DOAC-Remove® tableta, DOAK su praktično
inaktivisani što je omogućilo izvođenje analiza za LA i APC-R i
dobijanje 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 testiranja
trombofilije kod bolesnika lečenih primenom DOAK
VL  - 79
IS  - 12
SP  - 1248
EP  - 1254
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 = "Background/Aim. 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., Uvod/Cilj. 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) na
testove koagulacije tokom ispitivanja trombofilije. Metode.
Istraživanjem, sprovedenim od januara 2019. do juna 2020.
godine, obuhvaćeno je 30 bolesnika lečenih DOAK-om i
testiranih na trombofiliju zbog venskog tromboembolzma
(VTE). Bilo je 14 žena i 16 muškaraca, starosti od 23 do 63
godine (medijana 47,6 godina). Ispitivanje trombofilije izvršeno
je upotrebom DOAC-Remove® tableta (aktivni ugalj).
Upoređivani su rezultati pre i posle primene DOAC-Remove®.
Rezultati. Pozitivni rezultati za lupus antikoagulantni (LA) test
dobijeni su kod 20% bolesnika lečenih apiksabanom, kod
100% bolesnika lečenih dabigatranom i kod 70% lečenih riva-
roksabanom, a u uzorcima posle DOAC-Remove® pozitivnost
na LA dobijena je samo kod jednog bolesnika iz grupe lečnih
apiksabanom. Pre primene DOAC-Remove®, rezistencija na
aktivisani protein C (activated protein C resistance – APC-R) bila je
merljiva 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 posle
primene DOAC-Remove®, primećena je razlika u odnosu na
sve 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. Nakon
primene DOAC-Remove® tableta, DOAK su praktično
inaktivisani što je omogućilo izvođenje analiza za LA i APC-R i
dobijanje 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 testiranja
trombofilije kod bolesnika lečenih primenom DOAK",
volume = "79",
number = "12",
pages = "1248-1254",
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 . .

Clopidogrel High On-Treatment Platelet Reactivity in Patients with Carotid Artery Stenosis Undergoing Endarterectomy. A Pilot Study

Backović, Dragana; Ignjatović, Svetlana; Rakicević, Ljiljana; Novković, Mirjana; Kusić-Tisma, Jelena; Radojković, Dragica; Strugarević, Evgenija; Čalija, Branko; Radak, Đorđe; Kovac, Mirjana

(Bentham Science Publ Ltd, Sharjah, 2016)

TY  - JOUR
AU  - Backović, Dragana
AU  - Ignjatović, Svetlana
AU  - Rakicević, Ljiljana
AU  - Novković, Mirjana
AU  - Kusić-Tisma, Jelena
AU  - Radojković, Dragica
AU  - Strugarević, Evgenija
AU  - Čalija, Branko
AU  - Radak, Đorđe
AU  - Kovac, Mirjana
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2756
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
VL  - 14
IS  - 6
SP  - 563
EP  - 569
DO  - 10.2174/1570161114666160714103148
ER  - 
@article{
author = "Backović, Dragana and Ignjatović, Svetlana and Rakicević, Ljiljana and Novković, Mirjana and Kusić-Tisma, Jelena and Radojković, Dragica and Strugarević, Evgenija and Čalija, Branko and Radak, Đorđe and Kovac, 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",
volume = "14",
number = "6",
pages = "563-569",
doi = "10.2174/1570161114666160714103148"
}
Backović, D., Ignjatović, S., Rakicević, L., Novković, M., Kusić-Tisma, J., Radojković, D., Strugarević, E., Čalija, B., Radak, Đ.,& Kovac, 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, Rakicević L, Novković M, Kusić-Tisma J, Radojković D, Strugarević E, Čalija B, Radak Đ, Kovac 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, Rakicević, Ljiljana, Novković, Mirjana, Kusić-Tisma, Jelena, Radojković, Dragica, Strugarević, Evgenija, Čalija, Branko, Radak, Đorđe, Kovac, 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 . .
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Influence of Cyp2c19∗2 Gene Variant on Therapeutic Response during Clopidogrel Treatment in Patients with Carotid Artery Stenosis

Backović, Dragana; Ignjatović, Svetlana; Rakicević, Ljiljana; Kusić-Tisma, Jelena; Radojković, Dragica; Čalija, Branko; Strugarević, Evgenija; Radak, Đorđe; Kovac, Mirjana

(Društvo medicinskih biohemičara Srbije, Beograd i Versita, 2016)

TY  - JOUR
AU  - Backović, Dragana
AU  - Ignjatović, Svetlana
AU  - Rakicević, Ljiljana
AU  - Kusić-Tisma, Jelena
AU  - Radojković, Dragica
AU  - Čalija, Branko
AU  - Strugarević, Evgenija
AU  - Radak, Đorđe
AU  - Kovac, Mirjana
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2573
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 CYP2C19*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 CYP2C19*2 allele vs. wild type (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  - Influence of Cyp2c19∗2 Gene Variant on Therapeutic Response during Clopidogrel Treatment in Patients with Carotid Artery Stenosis
VL  - 35
IS  - 1
SP  - 26
EP  - 33
DO  - 10.1515/jomb-2015-0009
ER  - 
@article{
author = "Backović, Dragana and Ignjatović, Svetlana and Rakicević, Ljiljana and Kusić-Tisma, Jelena and Radojković, Dragica and Čalija, Branko and Strugarević, Evgenija and Radak, Đorđe and Kovac, Mirjana",
year = "2016",
abstract = "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 CYP2C19*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 CYP2C19*2 allele vs. wild type (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 = "Influence of Cyp2c19∗2 Gene Variant on Therapeutic Response during Clopidogrel Treatment in Patients with Carotid Artery Stenosis",
volume = "35",
number = "1",
pages = "26-33",
doi = "10.1515/jomb-2015-0009"
}
Backović, D., Ignjatović, S., Rakicević, L., Kusić-Tisma, J., Radojković, D., Čalija, B., Strugarević, E., Radak, Đ.,& Kovac, M.. (2016). Influence of Cyp2c19∗2 Gene Variant on Therapeutic Response during Clopidogrel Treatment in Patients with Carotid Artery Stenosis. in Journal of Medical Biochemistry
Društvo medicinskih biohemičara Srbije, Beograd i Versita., 35(1), 26-33.
https://doi.org/10.1515/jomb-2015-0009
Backović D, Ignjatović S, Rakicević L, Kusić-Tisma J, Radojković D, Čalija B, Strugarević E, Radak Đ, Kovac M. Influence of Cyp2c19∗2 Gene Variant on Therapeutic Response during Clopidogrel Treatment in Patients with Carotid Artery Stenosis. in Journal of Medical Biochemistry. 2016;35(1):26-33.
doi:10.1515/jomb-2015-0009 .
Backović, Dragana, Ignjatović, Svetlana, Rakicević, Ljiljana, Kusić-Tisma, Jelena, Radojković, Dragica, Čalija, Branko, Strugarević, Evgenija, Radak, Đorđe, Kovac, Mirjana, "Influence of Cyp2c19∗2 Gene Variant on Therapeutic Response during Clopidogrel Treatment in Patients with Carotid Artery Stenosis" in Journal of Medical Biochemistry, 35, no. 1 (2016):26-33,
https://doi.org/10.1515/jomb-2015-0009 . .
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