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 . .

TY  - JOUR
AU  - Lalić-Ćosić, Sanja
AU  - Dopsaj, Violeta
AU  - Kovač, Mirjana
AU  - Mandić-Marković, Vesna
AU  - Miković, Željko
AU  - Mobarrez, Fariborz
AU  - Antović, Aleksandra
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3997
AB  - Background: Pre-eclampsia (P-EC) is associated with systemic inflammation, endothelial dysfunction and hypercoagulability. The role of extracellular vesicles (EVs) in coagulation disturbances affecting the development and severity of P-EC remains elusive. We aimed to evaluate the concentration of EVs expressing phosphatidylserine (PS) and specific markers in relation to the thrombin and fibrin formation as well as fibrin clot properties, in pregnant women with P-EC in comparison to healthy pregnant women of similar gestational age. Methods: Blood samples of 30 pregnant women diagnosed with P-EC were collected on the morning following admission to hospital and after delivery (mean duration 5 days). The concentration of the PS-exposing EVs (PS+ EVs) from platelets (CD42a+, endothelial cells (CD62E+), and PS+ EVs expressing tissue factor (TF) and vascular cell adhesion molecule 1 (VCAM-1) were measured by flow cytometry. Further phenotyping of EVs also included expression of PlGF. Markers of maternal haemostasis were correlated with EVs concentration in plasma. Results: Preeclamptic pregnancy was associated with significantly higher plasma levels of PS+ CD42a+ EVs and PS+ VCAM-1+ EVs in comparison with normotensive pregnancy. P-EC patients after delivery had markedly elevated concentration of PS+ CD42a+ EVs, CD62E+ EVs, TF+ EVs, and VCAM-1+ EVs compared to those before delivery. Inverse correlation was observed between EVs concentrations (PS+, PS+ TF+, and PlGF+) and parameters of overall haemostatic potential (OHP) and fibrin formation, while PS+ VCAM-1+ EVs directly correlated with FVIII activity in plasma. Conclusion: Increased levels of PS+ EVs subpopulations in P-EC and their association with global haemostatic parameters, as well as with fibrin clot properties may suggest EVs involvement in intravascular fibrin deposition leading to subsequent microcirculation disorders.
PB  - Frontiers Media S.A.
T2  - Frontiers in Medicine
T1  - Phosphatidylserine Exposing Extracellular Vesicles in Pre-eclamptic Patients
VL  - 8
DO  - 10.3389/fmed.2021.761453
ER  - 

@article{
author = "Lalić-Ćosić, Sanja and Dopsaj, Violeta and Kovač, Mirjana and Mandić-Marković, Vesna and Miković, Željko and Mobarrez, Fariborz and Antović, Aleksandra",
year = "2021",
abstract = "Background: Pre-eclampsia (P-EC) is associated with systemic inflammation, endothelial dysfunction and hypercoagulability. The role of extracellular vesicles (EVs) in coagulation disturbances affecting the development and severity of P-EC remains elusive. We aimed to evaluate the concentration of EVs expressing phosphatidylserine (PS) and specific markers in relation to the thrombin and fibrin formation as well as fibrin clot properties, in pregnant women with P-EC in comparison to healthy pregnant women of similar gestational age. Methods: Blood samples of 30 pregnant women diagnosed with P-EC were collected on the morning following admission to hospital and after delivery (mean duration 5 days). The concentration of the PS-exposing EVs (PS+ EVs) from platelets (CD42a+, endothelial cells (CD62E+), and PS+ EVs expressing tissue factor (TF) and vascular cell adhesion molecule 1 (VCAM-1) were measured by flow cytometry. Further phenotyping of EVs also included expression of PlGF. Markers of maternal haemostasis were correlated with EVs concentration in plasma. Results: Preeclamptic pregnancy was associated with significantly higher plasma levels of PS+ CD42a+ EVs and PS+ VCAM-1+ EVs in comparison with normotensive pregnancy. P-EC patients after delivery had markedly elevated concentration of PS+ CD42a+ EVs, CD62E+ EVs, TF+ EVs, and VCAM-1+ EVs compared to those before delivery. Inverse correlation was observed between EVs concentrations (PS+, PS+ TF+, and PlGF+) and parameters of overall haemostatic potential (OHP) and fibrin formation, while PS+ VCAM-1+ EVs directly correlated with FVIII activity in plasma. Conclusion: Increased levels of PS+ EVs subpopulations in P-EC and their association with global haemostatic parameters, as well as with fibrin clot properties may suggest EVs involvement in intravascular fibrin deposition leading to subsequent microcirculation disorders.",
publisher = "Frontiers Media S.A.",
journal = "Frontiers in Medicine",
title = "Phosphatidylserine Exposing Extracellular Vesicles in Pre-eclamptic Patients",
volume = "8",
doi = "10.3389/fmed.2021.761453"
}

Lalić-Ćosić, S., Dopsaj, V., Kovač, M., Mandić-Marković, V., Miković, Ž., Mobarrez, F.,& Antović, A.. (2021). Phosphatidylserine Exposing Extracellular Vesicles in Pre-eclamptic Patients. in Frontiers in Medicine
Frontiers Media S.A.., 8.
https://doi.org/10.3389/fmed.2021.761453

Lalić-Ćosić S, Dopsaj V, Kovač M, Mandić-Marković V, Miković Ž, Mobarrez F, Antović A. Phosphatidylserine Exposing Extracellular Vesicles in Pre-eclamptic Patients. in Frontiers in Medicine. 2021;8.
doi:10.3389/fmed.2021.761453 .

Lalić-Ćosić, Sanja, Dopsaj, Violeta, Kovač, Mirjana, Mandić-Marković, Vesna, Miković, Željko, Mobarrez, Fariborz, Antović, Aleksandra, "Phosphatidylserine Exposing Extracellular Vesicles in Pre-eclamptic Patients" in Frontiers in Medicine, 8 (2021),
https://doi.org/10.3389/fmed.2021.761453 . .

TY  - JOUR
AU  - Lalić-Ćosić, Sanja
AU  - Dopsaj, Violeta
AU  - Kovač, Mirjana
AU  - Pruner, Iva
AU  - Littmann, Karin
AU  - Mandić-Marković, Vesna
AU  - Miković, Željko
AU  - Antović, Aleksandra
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3609
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-Blackwell
T2  - International Journal of Laboratory Hematology
T1  - Evaluation of global haemostatic assays and fibrin structure in patients with pre-eclampsia
VL  - 42
IS  - 3
SP  - 322
EP  - 330
DO  - 10.1111/ijlh.13183
ER  - 

@article{
author = "Lalić-Ćosić, Sanja and Dopsaj, Violeta and Kovač, Mirjana and Pruner, Iva and Littmann, Karin and Mandić-Marković, Vesna and Miković, Željko 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-Blackwell",
journal = "International Journal of Laboratory Hematology",
title = "Evaluation of global haemostatic assays and fibrin structure in patients with pre-eclampsia",
volume = "42",
number = "3",
pages = "322-330",
doi = "10.1111/ijlh.13183"
}

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

Lalić-Ćosić S, Dopsaj V, Kovač M, Pruner I, Littmann K, Mandić-Marković V, Miković Ž, 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-Ćosić, Sanja, Dopsaj, Violeta, Kovač, Mirjana, Pruner, Iva, Littmann, Karin, Mandić-Marković, Vesna, Miković, Željko, 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 . .