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Browsing by Author "Mitrovic, Mirjana (54972086700)"

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    Acquired von Willebrand syndrome in patients with Gaucher disease
    (2014)
    Mitrovic, Mirjana (54972086700)
    ;
    Elezovic, Ivo (12782840600)
    ;
    Miljic, Predrag (6604038486)
    ;
    Suvajdzic, Nada (7003417452)
    Although various coagulation abnormalities occur in patients with Gaucher disease (GD), von Willebrand factor (vWF) deficiency has rarely been reported. A retrospective review of six treatment naïve cases with GD and concomitant vWF deficiency over a 12-year-period in a single center is presented. All patients had a personal history of prior hemorrhages. Based on both reduced level of vWF antigen (vWF:Ag, range 14-56%) and ristocetin cofactor activity (vWF:RCo, range 12-53%), with a vWF:RCo/Ag ratio >0.7, the diagnosis of type 1 von Willebrand disease was made in all six cases. During enzyme replacement therapy (ERT) of a 2-year duration all patients normalized their vWF:Ag levels. Based on the positive ERT effect on vWF:Ag levels, vWF deficiency was assumed to be acquired. It should be noted that beside vWF deficiency four patients with GD exhibited mild thrombocytopenia (range 81-131×109/L) and three had additional hemostatic defects (reduced collagen platelet aggregation, FV, FXI and FXII deficiencies). © 2013 Elsevier Inc.
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    Acquired von Willebrand syndrome in patients with Gaucher disease
    (2014)
    Mitrovic, Mirjana (54972086700)
    ;
    Elezovic, Ivo (12782840600)
    ;
    Miljic, Predrag (6604038486)
    ;
    Suvajdzic, Nada (7003417452)
    Although various coagulation abnormalities occur in patients with Gaucher disease (GD), von Willebrand factor (vWF) deficiency has rarely been reported. A retrospective review of six treatment naïve cases with GD and concomitant vWF deficiency over a 12-year-period in a single center is presented. All patients had a personal history of prior hemorrhages. Based on both reduced level of vWF antigen (vWF:Ag, range 14-56%) and ristocetin cofactor activity (vWF:RCo, range 12-53%), with a vWF:RCo/Ag ratio >0.7, the diagnosis of type 1 von Willebrand disease was made in all six cases. During enzyme replacement therapy (ERT) of a 2-year duration all patients normalized their vWF:Ag levels. Based on the positive ERT effect on vWF:Ag levels, vWF deficiency was assumed to be acquired. It should be noted that beside vWF deficiency four patients with GD exhibited mild thrombocytopenia (range 81-131×109/L) and three had additional hemostatic defects (reduced collagen platelet aggregation, FV, FXI and FXII deficiencies). © 2013 Elsevier Inc.
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    Acute leukemia and SARS-CoV-2 infection: clinical characteristics and risk factors for mortality
    (2021)
    Mitrovic, Mirjana (54972086700)
    ;
    Pantic, Nikola (57221630977)
    ;
    Sabljic, Nikica (57221634280)
    ;
    Vucic, Miodrag (9840397700)
    ;
    Bukumiric, Zoran (36600111200)
    ;
    Virijevic, Marijana (36969618100)
    ;
    Pravdic, Zlatko (57221636770)
    ;
    Rajic, Jovan (57435044600)
    ;
    Todorovic-Balint, Milena (55773026600)
    ;
    Vidovic, Ana (6701313789)
    ;
    Suvajdzic-Vukovic, Nada (36446767400)
    Patients with acute leukemia (AL) have a high mortality rate from coronavirus disease 2019 (COVID-19). However, studies including patients with AL and COVID-19 are few. Fifty-one patients with AL and COVID-19 were included in our study. The mortality rate was 17/51 (29.4%). In all cases, death was associated with COVID-19 pneumonia. The major driver of outcome was the disease status (worse outcome was observed in newly diagnosed (OR, 6.00; 95% CI, 1.133–15.188) and patients with bone marrow aplasia (OR 4.148 [95% CI 1.133–15.188])). Higher mortality rate was associated with lower platelet count, prolonged PT, higher ISTH DIC score, CRP and LDH. Moreover, careful risk-benefit assessment regarding the continuation of anticancer therapy is required in patients receiving nonintensive and supportive therapy. Considering the high frequency of intrahospital viral transmission (50.98%), isolation of AL patients in single rooms, and permanent symptom monitoring and testing should be prioritized. © 2021 Informa UK Limited, trading as Taylor & Francis Group.
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    Acute leukemia and SARS-CoV-2 infection: clinical characteristics and risk factors for mortality
    (2021)
    Mitrovic, Mirjana (54972086700)
    ;
    Pantic, Nikola (57221630977)
    ;
    Sabljic, Nikica (57221634280)
    ;
    Vucic, Miodrag (9840397700)
    ;
    Bukumiric, Zoran (36600111200)
    ;
    Virijevic, Marijana (36969618100)
    ;
    Pravdic, Zlatko (57221636770)
    ;
    Rajic, Jovan (57435044600)
    ;
    Todorovic-Balint, Milena (55773026600)
    ;
    Vidovic, Ana (6701313789)
    ;
    Suvajdzic-Vukovic, Nada (36446767400)
    Patients with acute leukemia (AL) have a high mortality rate from coronavirus disease 2019 (COVID-19). However, studies including patients with AL and COVID-19 are few. Fifty-one patients with AL and COVID-19 were included in our study. The mortality rate was 17/51 (29.4%). In all cases, death was associated with COVID-19 pneumonia. The major driver of outcome was the disease status (worse outcome was observed in newly diagnosed (OR, 6.00; 95% CI, 1.133–15.188) and patients with bone marrow aplasia (OR 4.148 [95% CI 1.133–15.188])). Higher mortality rate was associated with lower platelet count, prolonged PT, higher ISTH DIC score, CRP and LDH. Moreover, careful risk-benefit assessment regarding the continuation of anticancer therapy is required in patients receiving nonintensive and supportive therapy. Considering the high frequency of intrahospital viral transmission (50.98%), isolation of AL patients in single rooms, and permanent symptom monitoring and testing should be prioritized. © 2021 Informa UK Limited, trading as Taylor & Francis Group.
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    Application of Rotational Thromboelastometry in Patients with Acute Promyelocytic Leukemia
    (2022)
    Sabljic, Nikica (57221634280)
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    Pantic, Nikola (57221630977)
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    Virijevic, Marijana (36969618100)
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    Bukumiric, Zoran (36600111200)
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    Novakovic, Tina (57191900614)
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    Pravdic, Zlatko (57221636770)
    ;
    Rajic, Jovan (57435044600)
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    Vidovic, Ana (6701313789)
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    Suvajdzic, Nada (7003417452)
    ;
    Jaradeh, Mark (57190871817)
    ;
    Fareed, Jawed (7102367063)
    ;
    Antic, Darko (23979576100)
    ;
    Mitrovic, Mirjana (54972086700)
    Introduction: Hemorrhagic early death (HED) remains a major cause of treatment failure among patients with acute promyelocytic leukemia (APL). We aimed to investigate the prognostic potential of rotational thromboelastometry (ROTEM) for bleeding in patients with APL. Materials and Methods: 31 newly-diagnosed APL patients (median age of 40 years; 14 female/17 male) that underwent treatment at the Clinic of Hematology UCCS from 2016-2020 with all-trans retinoic acid and anthracyclines were recruited. CBCs (complete blood count), conventional coagulation tests (CCTs), and ROTEM parameters obtained before treatment initiation were evaluated. Results: All patients demonstrated at least one ROTEM parameter out of the reference range. ROTEM parameters associated with significant hemorrhage were EXTEM clotting time (CT) (P = 0.041) and INTEM amplitude 10 (A10) (P = 0.039), however, only EXTEM CT (P = 0.036) was associated with HED. Among CBCs and CCTs, only platelets were associated with significant bleeding (P = 0.015), while D-dimer was associated with both bleeding and HED (P = 0.001 and P = 0.002, respectively). Conclusion: Our results indicate that ROTEM parameters may reveal hypocoagulability in APL patients and have the potential to improve current hemorrhage prognostic methods. Additionally, these results suggest the combination of ROTEM and CCTs might be useful in identifying patients at risk for HED. © The Author(s) 2022.
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    Arterial Thrombosis in Patients with Acute Myeloid Leukemia: Incidence and Risk Factors
    (2023)
    Mitrovic, Mirjana (54972086700)
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    Pantic, Nikola (57221630977)
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    Sabljic, Nikica (57221634280)
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    Bukumiric, Zoran (36600111200)
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    Virijevic, Marijana (36969618100)
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    Pravdic, Zlatko (57221636770)
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    Cvetkovic, Mirjana (58716866000)
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    Rajic, Jovan (57435044600)
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    Bodrozic, Jelena (55895034400)
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    Milosevic, Violeta (24399200100)
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    Todorovic-Balint, Milena (55773026600)
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    Vidovic, Ana (6701313789)
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    Suvajdzic-Vukovic, Nada (36446767400)
    ;
    Antic, Darko (23979576100)
    Background: Patients with hematological malignancies have an increased risk of arterial thrombotic events (ATEs) after diagnosis, compared to matched controls without cancer. However, data about incidence and risk factors for ATE development in patients with acute myeloid leukemia (AML) are missing. Aim: The objectives of this study were to determine the incidence of ATE in non-promyelocytic-AML patients and to define the potential risk factors for ATE development. Methods: We conducted a retrospective cohort study of adult patients with newly diagnosed AML. The primary outcome was the occurrence of confirmed ATE, defined as myocardial infarction, stroke or critical limb ischemia. Results: Out of 626 eligible AML patients, 18 (2.9%) patients developed ATE in the median time of 3 (range: 0.23–6) months. Half of these patients died due to ATE complications. Five parameters were predictors of ATE: BMI > 30 (p = 0.000, odds ratio [OR] 20.488, 95% CI: 6.581–63.780), prior history of TE (p = 0.041, OR 4.233, 95% CI: 1.329–13.486), presence of comorbidities (p = 0.027, OR 5.318, 95% CI: 1.212–23.342), presence of cardiovascular comorbidities (p < 0.0001, OR 8.0168, 95% CI: 2.948–21.800) and cytogenetic risk score (p = 0.002, OR 2.113, 95% CI: 1.092–5.007). Conclusions: Our study showed that patients with AML are at increased risk of ATE. The risk was increased in patients with cardiovascular comorbidities, previous thrombosis, adverse cytogenetic risk as well as BMI > 30. © 2023 by the authors.
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    Arterial Thrombosis in Patients with Acute Myeloid Leukemia: Incidence and Risk Factors
    (2023)
    Mitrovic, Mirjana (54972086700)
    ;
    Pantic, Nikola (57221630977)
    ;
    Sabljic, Nikica (57221634280)
    ;
    Bukumiric, Zoran (36600111200)
    ;
    Virijevic, Marijana (36969618100)
    ;
    Pravdic, Zlatko (57221636770)
    ;
    Cvetkovic, Mirjana (58716866000)
    ;
    Rajic, Jovan (57435044600)
    ;
    Bodrozic, Jelena (55895034400)
    ;
    Milosevic, Violeta (24399200100)
    ;
    Todorovic-Balint, Milena (55773026600)
    ;
    Vidovic, Ana (6701313789)
    ;
    Suvajdzic-Vukovic, Nada (36446767400)
    ;
    Antic, Darko (23979576100)
    Background: Patients with hematological malignancies have an increased risk of arterial thrombotic events (ATEs) after diagnosis, compared to matched controls without cancer. However, data about incidence and risk factors for ATE development in patients with acute myeloid leukemia (AML) are missing. Aim: The objectives of this study were to determine the incidence of ATE in non-promyelocytic-AML patients and to define the potential risk factors for ATE development. Methods: We conducted a retrospective cohort study of adult patients with newly diagnosed AML. The primary outcome was the occurrence of confirmed ATE, defined as myocardial infarction, stroke or critical limb ischemia. Results: Out of 626 eligible AML patients, 18 (2.9%) patients developed ATE in the median time of 3 (range: 0.23–6) months. Half of these patients died due to ATE complications. Five parameters were predictors of ATE: BMI > 30 (p = 0.000, odds ratio [OR] 20.488, 95% CI: 6.581–63.780), prior history of TE (p = 0.041, OR 4.233, 95% CI: 1.329–13.486), presence of comorbidities (p = 0.027, OR 5.318, 95% CI: 1.212–23.342), presence of cardiovascular comorbidities (p < 0.0001, OR 8.0168, 95% CI: 2.948–21.800) and cytogenetic risk score (p = 0.002, OR 2.113, 95% CI: 1.092–5.007). Conclusions: Our study showed that patients with AML are at increased risk of ATE. The risk was increased in patients with cardiovascular comorbidities, previous thrombosis, adverse cytogenetic risk as well as BMI > 30. © 2023 by the authors.
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    CAN PHARMACOGENETICS IMPACT THE THERAPEUTIC EFFECT OF CYTARABINE AND ANTHRACYCLINES IN ADULT ACUTE MYELOID LEUKAEMIA PATIENTS? A SERBIAN EXPERIENCE; [DA LI FARMAKOGENETIKA IMA UTICAJ NA ISHOD LEČENJA ODRASLIH PACIJENATA SA AKUTNOM MIJELOIDNOM LEUKEMIJOM LEČENIH PRIMENOM CITARABINA I ANTRACIKLINA? SRPSKO ISKUSTVO]
    (2024)
    Pravdic, Zlatko (57221636770)
    ;
    Vukovic, Nada Suvajdzic (36446767400)
    ;
    Virijevic, Marijana (36969618100)
    ;
    Mitrovic, Mirjana (54972086700)
    ;
    Pantic, Nikola (57221630977)
    ;
    Sabljic, Nikica (57221634280)
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    Pavlovic, Djordje (57409501100)
    ;
    Marjanovic, Irena (57189225697)
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    Bukumiric, Zoran (36600111200)
    ;
    Vidovic, Ana (6701313789)
    ;
    Jakovic, Ljubomir (21742748500)
    ;
    Pavlovic, Sonja (7006514877)
    ;
    Gasic, Vladimir (57095898600)
    Background: Cytarabine-anthracycline-based induction chemotherapy remains the standard of care for remission induction among patients with newly diagnosed acute myeloid leukaemia (AML). There are remarkable differences in therapy response among AML patients. This fact could be partly explained by the patients’ genetic variability related to the metabolic paths of cytarabine and anthracyclines. This study aims to evaluate the effect of variants in pharmacogenes SLC29A1, DCK, ABCB1, GSTM1, and GSTT1, as well as laboratory and AML-related parameters on clinical outcomes in adult AML patients. Methods: A total of 100 AML patients were included in the study. Pharmacogenetic variants SLC29A1 rs9394992, DCK rs12648166, ABCB1 rs2032582, and GSTM1 and GSTT1 gene deletions were detected by methodology based on PCR, fragment analysis and direct sequencing. The methods of descriptive and analytic statistics were used. Survival analysis was done using the Kaplan-Meier method using the Log-Rank test. Results: This is the first study of adult AML pharmacogenetics in the Serbian population. Clinical outcomes in our cohort of AML patients were not impacted by analysed variants in SLC29A1, DCK, ABCB1 and GSTT1, and GSTM1 genes, independently or in combinations. Achievement of complete remission was identified as an independent prognostic indicator of clinical outcome. Conclusions: The population-specific genomic profile has to be considered in pharmacogenetics. Since the data on AML pharmacogenetics in European populations is limited, our results contribute to knowledge in this field and strongly indicate that a high-throughput approach must be applied to find particular pharmacogenetic markers of AML in the European population. © 2024 Society of Medical Biochemists of Serbia. All rights reserved.
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    CAN PHARMACOGENETICS IMPACT THE THERAPEUTIC EFFECT OF CYTARABINE AND ANTHRACYCLINES IN ADULT ACUTE MYELOID LEUKAEMIA PATIENTS? A SERBIAN EXPERIENCE; [DA LI FARMAKOGENETIKA IMA UTICAJ NA ISHOD LEČENJA ODRASLIH PACIJENATA SA AKUTNOM MIJELOIDNOM LEUKEMIJOM LEČENIH PRIMENOM CITARABINA I ANTRACIKLINA? SRPSKO ISKUSTVO]
    (2024)
    Pravdic, Zlatko (57221636770)
    ;
    Vukovic, Nada Suvajdzic (36446767400)
    ;
    Virijevic, Marijana (36969618100)
    ;
    Mitrovic, Mirjana (54972086700)
    ;
    Pantic, Nikola (57221630977)
    ;
    Sabljic, Nikica (57221634280)
    ;
    Pavlovic, Djordje (57409501100)
    ;
    Marjanovic, Irena (57189225697)
    ;
    Bukumiric, Zoran (36600111200)
    ;
    Vidovic, Ana (6701313789)
    ;
    Jakovic, Ljubomir (21742748500)
    ;
    Pavlovic, Sonja (7006514877)
    ;
    Gasic, Vladimir (57095898600)
    Background: Cytarabine-anthracycline-based induction chemotherapy remains the standard of care for remission induction among patients with newly diagnosed acute myeloid leukaemia (AML). There are remarkable differences in therapy response among AML patients. This fact could be partly explained by the patients’ genetic variability related to the metabolic paths of cytarabine and anthracyclines. This study aims to evaluate the effect of variants in pharmacogenes SLC29A1, DCK, ABCB1, GSTM1, and GSTT1, as well as laboratory and AML-related parameters on clinical outcomes in adult AML patients. Methods: A total of 100 AML patients were included in the study. Pharmacogenetic variants SLC29A1 rs9394992, DCK rs12648166, ABCB1 rs2032582, and GSTM1 and GSTT1 gene deletions were detected by methodology based on PCR, fragment analysis and direct sequencing. The methods of descriptive and analytic statistics were used. Survival analysis was done using the Kaplan-Meier method using the Log-Rank test. Results: This is the first study of adult AML pharmacogenetics in the Serbian population. Clinical outcomes in our cohort of AML patients were not impacted by analysed variants in SLC29A1, DCK, ABCB1 and GSTT1, and GSTM1 genes, independently or in combinations. Achievement of complete remission was identified as an independent prognostic indicator of clinical outcome. Conclusions: The population-specific genomic profile has to be considered in pharmacogenetics. Since the data on AML pharmacogenetics in European populations is limited, our results contribute to knowledge in this field and strongly indicate that a high-throughput approach must be applied to find particular pharmacogenetic markers of AML in the European population. © 2024 Society of Medical Biochemists of Serbia. All rights reserved.
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    Clinical and laboratory characteristics of cyclic thrombocytopenia: An observational study
    (2020)
    Steinbrecher, Oskar (57201450692)
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    Mitrovic, Mirjana (54972086700)
    ;
    Eischer, Lisbeth (24472457400)
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    Šinkovec, Hana (57194406834)
    ;
    Eichinger, Sabine (7005214951)
    ;
    Kyrle, Paul A. (7005143085)
    [No abstract available]
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    Complex haemostatic abnormalities as a cause of bleeding after neurosurgery in a patient with Gaucher disease
    (2015)
    Mitrovic, Mirjana (54972086700)
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    Elezovic, Ivo (12782840600)
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    Grujicic, Danica (7004438060)
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    Miljic, Predrag (6604038486)
    ;
    Suvajdzic, Nada (7003417452)
    We report a treatment-naïve patient with Gaucher disease (GD) who experienced repeated bleeding after three neurosurgeries for a brain tumour, identified as an oligoastrocytoma. The patient had normal values on basic haemostatic tests: prothrombin time, 75-105%; activated partial thromboplastin time, 30.3-34 s; and mild thrombocytopaenia, 96-115 × 109cells/l. However, additional tests showed mild von Willebrand factor (vWF) deficiency (vWF antigen, 56%; vWF ristocetin cofactor, 49%; factor VIII [FVIII], 54%) and abnormal collagen-mediated platelet aggregation (0.45-0.55). Bleeding control was achieved after vWF/FVIII concentrate and platelet transfusions. This case raises questions about the safe platelet count and basic haemostatic tests for assessing bleeding risk in patients with GD prior to surgery. In patients with GD, a minimum haemostatic evaluation should include platelet count and basic haemostatic tests such as fibrinogen, prothrombin time, activated partial thromboplastin time as well as platelet function tests and assessing vWF and FVIII levels. Specific coagulation factors or platelet function deficiencies should be corrected with factor concentrates or platelet transfusions. © 2014 Informa UK Ltd.
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    Coronavirus disease 2019 in patients with chronic immune thrombocytopenia on thrombopoietin receptor agonists: new perspectives and old challenges
    (2022)
    Pantic, Nikola (57221630977)
    ;
    Suvajdzic-Vukovic, Nada (36446767400)
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    Virijevic, Marijana (36969618100)
    ;
    Pravdic, Zlatko (57221636770)
    ;
    Sabljic, Nikica (57221634280)
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    Adzic-Vukicevic, Tatjana (56888756300)
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    Mitrovic, Mirjana (54972086700)
    There are limited data on the impact of severe acute respiratory syndrome corona virus 2 infection in patients previously diagnosed with primary immune thrombocytopenia (ITP) on thrombopoietin receptor agonist therapy (TPO-RA). Seven chronic ITP patients who had contracted COVID-19 and had been treated with TPO-RA are included in the study. Demographic, ITP treatment and comorbidities data were collected retrospectively from patients' medical records. Data regarding clinical course of COVID-19 were collected prospectively. During the infection, all patients had platelet count higher than average, and platelet count peak was mainly observed on day 7. For that reason, therapy modification was required. However, platelet count increment was transient in most ITP patients. One patient developed pulmonary embolism despite the use of therapeutic dose of anticoagulants. One patient died of respiratory failure whereas another developed rebound thrombocytopenia after the infection and consequential intracerebral hemorrhage. Careful platelet count monitoring and therapy management are needed in chronic ITP patients on TPO-RAs with COVID-19. © 2021 Wolters Kluwer Health, Inc. All rights reserved.
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    COVID-19 Presented with Deep Vein Thrombosis in a Patient with Paroxysmal Nocturnal Haemoglobinuria
    (2021)
    Pravdic, Zlatko (57221636770)
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    Mitrovic, Mirjana (54972086700)
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    Bogdanovic, Andrija (6603686934)
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    Virijevic, Marijana (36969618100)
    ;
    Sabljic, Nikica (57221634280)
    ;
    Pantic, Nikola (57221630977)
    ;
    Vukovic, Nada Suvajdzic (36446767400)
    Paroxysmal nocturnal haemoglobinuria (PNH) is a rare, acquired clonal haematological disease characterized by complement-mediated haemolysis, bone marrow failure and venous thrombosis. Anticomplement therapy eculizumab improves survival and reduces complications. Severe acute respiratory distress syndrome corona virus 2 (SARS-CoV-2) disease 2019 (COVID-19) is associated with high incidence of both venous and arterial thrombosis in hospitalized patients with pneumonia. Deep venous thrombosis (DVT) as the presenting symptom of COVID-19 is a rare event. We describe a well-controlled PNH patient on eculizumab for more than 5 years who presented with DVT, while on warfarin, as the first sign of COVID-19. To our knowledge, this is the first described case of DVT in a PNH patient with COVID-19. © 2021 Georg Thieme Verlag. All rights reserved.
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    Covid-19-associated pulmonary aspergillosis in patients with acute leukemia: A single-center study
    (2021)
    Rajic, Jovan (57435044600)
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    Gmizic, Ivana (57205466405)
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    Gunjak, Tara (57314224900)
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    Milosevic, Violeta (24399200100)
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    Pantic, Nikola (57221630977)
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    Sabljic, Nikica (57221634280)
    ;
    Mitrovic, Mirjana (54972086700)
    ;
    Stefanovic, Aleksandra Djuric (59026442300)
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    Lazic, Ljubica (36093093100)
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    Jovanovic, Snezana (7102384849)
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    Milošević, Ivana (58456808200)
    ;
    Barac, Aleksandra (55550748700)
    ;
    Vidovic, Ana (6701313789)
    Patients with coronavirus disease 19 (COVID-19) have increased susceptibility to secondary respiratory infections including invasive pulmonary aspergillosis (IPA). COVID-19-associated pulmonary aspergillosis (CAPA) is difficult to diagnose and can be associated with increased mortality especially in severe immunodeficiency such as hematological malignancies. Our study evaluates IPA in COVID-19 patients defined as COVID-19-CAPA among patients with acute leukemia (AL). A retrospective single-center study analyzed 46 patients with COVID-19 infection and acute leukemia, admitted to the Clinic for Haematology, Clinical Center of Serbia, Belgrade between the 2 April 2020 and 15 May 2021. During hospitalization, all participants were diagnosed with probable IPA according to the previous consensus definitions. Positive serology and galactomannan (GM) detection values in bronchoalveolar lavage (BAL) and serum were used as microbiological criteria. COVID-19 associated probable IPA was found in 22% (9/41) tested patients, where serum GM and IgM anti-Aspergillus antibodies were positive in 12% (5/41) and 10% (4/41) had positive serology for aspergillosis. One patient died while eight recovered during follow-up. Our study showed that COVID-19 might be a risk factor for IPA development in patients with AL. Early diagnosis and prompt treatment are required as reported mortality rates are high. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
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    Covid-19-associated pulmonary aspergillosis in patients with acute leukemia: A single-center study
    (2021)
    Rajic, Jovan (57435044600)
    ;
    Gmizic, Ivana (57205466405)
    ;
    Gunjak, Tara (57314224900)
    ;
    Milosevic, Violeta (24399200100)
    ;
    Pantic, Nikola (57221630977)
    ;
    Sabljic, Nikica (57221634280)
    ;
    Mitrovic, Mirjana (54972086700)
    ;
    Stefanovic, Aleksandra Djuric (59026442300)
    ;
    Lazic, Ljubica (36093093100)
    ;
    Jovanovic, Snezana (7102384849)
    ;
    Milošević, Ivana (58456808200)
    ;
    Barac, Aleksandra (55550748700)
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    Vidovic, Ana (6701313789)
    Patients with coronavirus disease 19 (COVID-19) have increased susceptibility to secondary respiratory infections including invasive pulmonary aspergillosis (IPA). COVID-19-associated pulmonary aspergillosis (CAPA) is difficult to diagnose and can be associated with increased mortality especially in severe immunodeficiency such as hematological malignancies. Our study evaluates IPA in COVID-19 patients defined as COVID-19-CAPA among patients with acute leukemia (AL). A retrospective single-center study analyzed 46 patients with COVID-19 infection and acute leukemia, admitted to the Clinic for Haematology, Clinical Center of Serbia, Belgrade between the 2 April 2020 and 15 May 2021. During hospitalization, all participants were diagnosed with probable IPA according to the previous consensus definitions. Positive serology and galactomannan (GM) detection values in bronchoalveolar lavage (BAL) and serum were used as microbiological criteria. COVID-19 associated probable IPA was found in 22% (9/41) tested patients, where serum GM and IgM anti-Aspergillus antibodies were positive in 12% (5/41) and 10% (4/41) had positive serology for aspergillosis. One patient died while eight recovered during follow-up. Our study showed that COVID-19 might be a risk factor for IPA development in patients with AL. Early diagnosis and prompt treatment are required as reported mortality rates are high. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
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    Deep venous thrombosis in patients with atresia of the inferior vena cava and right kidney hypoplasia (KILT syndrome): Systematic review of the literature
    (2024)
    Pantic, Nikola (57221630977)
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    Cvetkovic, Mirjana (58716866000)
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    Milin-Lazovic, Jelena (57023980700)
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    Vukmirovic, Jelica (58973602200)
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    Pavlovic, Aleksandar (58553335800)
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    Virijevic, Marijana (36969618100)
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    Pravdic, Zlatko (57221636770)
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    Kozarac, Sofija (58973969700)
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    Sabljic, Nikica (57221634280)
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    Suvajdzic-Vukovic, Nada (36446767400)
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    Dragas, Marko (25027673300)
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    Mitrovic, Mirjana (54972086700)
    Inferior vena cava (IVC) anomalies are uncommon congenital causes of deep vein thrombosis (DVT). KILT syndrome (kidney and IVC abnormalities with leg thrombosis) has only been described as case reports in the literature. Therefore, the characteristics, evaluation, and management of patients with KILT syndrome have not yet been standardized. This study aimed to systematically review and analyze the clinical and radiographic data and treatment of previously reported cases of KILT syndrome. In this systematic review, we performed a literature search of the PubMed, Scopus, and Web of Science databases in December 2023, with no restrictions on the publication date. After duplicate extractions, 4195 articles were screened. Case reports and case series reporting on KILT syndrome were included. In addition to previously published cases, we included a new case of a previously healthy 25-year-old man with KILT syndrome in the analysis. A total of 34 cases were therefore included in this study. The majority (76.5%) were male patients with a median age of 24 years. In most patients, unprovoked bilateral iliofemoral thrombosis was diagnosed, and 64.7% had left kidney abnormalities. Our study suggests that anomalies of the IVC should be suspected in all young patients, especially male patients, with proximal, recurrent, or idiopathic DVT. If an IVC anomaly is confirmed, the kidneys should be examined to monitor and preserve healthy kidneys in cases of KILT syndrome. The data collected from all patients emphasize the requirement of long-term anticoagulation and risk factor control. Surgical measures may be effective for treating symptomatic refractory cases. © The Author(s) 2024.
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    Early Prediction and Streamline of Nucleophosmin Mutation Status in Acute Myeloid Leukemia Using Cup-Like Nuclear Morphology
    (2024)
    Jakovic, Ljubomir (21742748500)
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    Djordjevic, Vesna (57215460423)
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    Kraguljac Kurtovic, Nada (37037758700)
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    Virijevic, Marijana (36969618100)
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    Mitrovic, Mirjana (54972086700)
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    Trajkovic, Lazar (59347542100)
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    Vidovic, Ana (6701313789)
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    Bogdanovic, Andrija (6603686934)
    Background and Objectives: With the advent of novel therapies for nucleophosmin gene (NPM1)-mutated acute myeloid leukemia (AML), there is a growing need for the reliable prediction of NPM1 mutations. This study explored the role of cytomorphological features in the early prediction of NPM1-mutated AML. Materials and Methods: Altogether, 212 de novo AML cases with normal karyotypes, diagnosed and treated at a single institution within 5 years (2018–2023), were retrospectively evaluated. A final diagnosis of NPM1-mutated AML, based on the World Health Organization (WHO) integrated criteria, including real-time based identification of NPM1 mutation and normal karyotype, was established in 83/212 (39.15%) cases. Results: Cup-like blasts (CLBs), a cytomorphological feature suggestive of NPM1-mutated AML, were detected in 56/83 (67%) patients. Most cases (44/56, 78.6%) had CLB ≥ 10%. In total, 27 of 83 AML NPM1-mutated patients had no CLB morphology (missed call). Additionally, two of 212 had CLB morphology without confirmed NPM1 mutation (wrong call). The positive/negative predictive values of cytomorphological evaluation for CLB ≥ 10% were 95.7%/75.6%, with sensitivity/specificity of 53%/98.5%, while the accuracy was 80.7%. We noted an increased percentage of CLBs (≥15%) in 77.8% and 50% of patients with AML without and with granulocytic maturation, respectively (the specificity for NPM1 mutation prediction was 100%). CLB was associated with fms-like tyrosine kinase 3 (FLT3) mutation (p = 0.03), but, without statistical significance for CLB ≥ 10% and CLB ≥ 15%. Conclusions: Our investigation confirmed that the morphological identification of CLB at diagnosis represents a reliable and easily reproducible tool for the early prediction of NPM1 mutations, enabling a streamlined genetic work-up for its confirmation. This may facilitate considering the early administration of individualized therapies by clinicians for specific patients. © 2024 by the authors.
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    Haemostatic abnormalities in treatment-nave patients with Type 1 Gaucher's disease
    (2012)
    Mitrovic, Mirjana (54972086700)
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    Antic, Darko (23979576100)
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    Elezovic, Ivo (12782840600)
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    Janic, Dragana (15729368500)
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    Miljic, Predrag (6604038486)
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    Sumarac, Zorica (6603643930)
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    Nikolic, Tanja (54978526200)
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    Suvajdzic, Nada (7003417452)
    There is a paucity of data on the effects of enzyme replacement therapy (ERT) on the coagulation abnormalities and platelet function of patients with Gaucher's disease (GDPs) and much of this data are controversial. This study investigates the haemostatic parameters in treatment-nave GDPs and the effects of ERT. 31 Serbian treatment-nave type 1 GDPs (M/F 17/14; median age 49 years, splenectomized 9/31) were studied. The complete blood count, prothrombin time (PT), activated partial tromboplastin time (aPTT) and coagulation factors were measured using the standard methods. Platelet aggregation was assessed with a whole-blood aggregometer. Splenic volumes were assessed using computer tomography. Twenty-one patients were treated with ERT (Imiglucerase). The haemostatic parameters were assessed after 6, 12 and 24 months (ERT 6, 12, 24). Initially bleeding episodes were registered in 10/31 GDPs. Median platelet count was 108×10 9/L; 22/31 GDPs were thrombocytopenic. The PT and aPTT values were abnormal in 16/31 and 13/31 GDPs, respectively. Platelet aggregation abnormalities were recorded in 19/31GDPs. Median platelet aggregation was reduced in response to adenosine-diphosphate 5mol/L (ADP 5 0.46) and collagen 5mol/L (Col5 0.47). Splenic volume inversely correlated with the platelet count and a reduced response to arachidonic acid (AA), Col5 and ADP5 (p<0.05). The splenectomized GDPs had a significantly lower platelet aggregation to Col 10 (p<0.05). Bleeding GDPs had a significantly lower platelet count, higher chitotriosidase levels and a greater splenic volume compared to non-bleeding patients (p<0.01). ERT: The number of bleeding GDPs had significantly decreased by ERT 6 (1/10; p<0.01). The platelet count had significantly increased by ERT 6 (ERT 6 180×10 9/L, p<0.01). The PT increased significantly from ERT0 to ERT 24 (PT0 65%, PT 24 81%; p<0.05). The von Willebrand factor had increased significantly by ERT 6 and ERT 24 (ERT0 56%, ERT 6 70%, ERT 12 70%, ERT 24 86%; p<0.01). The number of GDPs with abnormal platelet aggregation had decreased significantly by ERT 6 (10/19; p<0.05). Platelet aggregation on ADP 10 and AA significantly increased by ERT 6 (ADP 10: ERT 0 0.75, ERT 6 0.8 p<0.01; AA: ERT0 0.7, ERT 6 0.8 p<0.05). In conclusion, platelet dysfunction and coagulation abnormalities were found in a considerable number of our GDPs. The absence of severe bleeding episodes suggests that the haemostatic system is sufficiently balanced and therefore the exact mechanism of the etiology of these abnormalities need to be fully clarified. ERT resulted in the cessation of bleeding and marked increase in platelet count, PT, vWF and platelet aggregation. © 2012 Informa UK Ltd. All rights reserved.
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    Hemorrhage in acute promyelocytic leukemia—fibrinolysis in focus
    (2024)
    Sabljic, Nikica (57221634280)
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    Thachil, Jecko (23029666900)
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    Pantic, Nikola (57221630977)
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    Mitrovic, Mirjana (54972086700)
    Coagulopathy continues to be a major challenge in the management of patients with acute promyelocytic leukemia (APL). Novel differentiating agents have led to improved survival in these patients, but perturbations in coagulation continue to have an impact on their prognosis. The most worrisome of coagulation disturbances is bleeding, which is not an uncommon cause of early death in APL. Despite this, there are no consistent predictors of this high risk of fatal hemorrhage in APL. In this context, the fibrinolytic system has been identified as a crucial role player in APL coagulopathy. However, the current guidelines for the management of APL give little regard to tests that measure the fibrinolytic system while giving more importance to close monitoring of conventional coagulation tests and platelet counts to identify the coagulopathy. More recently, viscoelastic tests have come to usefulness in determining global hemostasis and have been widely used for “diagnosing” hyperfibrinolysis in selected clinical settings. In this review, we attempt to describe risk assessment models for diagnosing APL coagulopathy, describe the possible application of viscoelastic tests in this setting, and persuade clinicians to reconsider the use of antifibrinolytics to improve survival of APL patients. © 2024 The Authors
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    Incidence, risk factors, and outcome of asymptomatic central nervous system involvement in adult patients with acute myeloid leukemia
    (2024)
    Virijevic, Marijana (36969618100)
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    Kraguljac-Kurtovic, Nada (37037758700)
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    Mitrovic, Mirjana (54972086700)
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    Jakovic, Ljubomir (21742748500)
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    Bukumuric, Zoran (58855087200)
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    Pantic, Nikola (57221630977)
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    Sabljic, Nikica (57221634280)
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    Pravdic, Zlatko (57221636770)
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    Cvetkovic, Mirjana (58716866000)
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    Knezevic, Vesna (56806620700)
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    Dragovic-Ivancevic, Tijana (56806924600)
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    Djunić, Irena (23396871100)
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    Rajic, Jovan (57435044600)
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    Milosevic, Violeta (24399200100)
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    Todorovic-Balint, Milena (55773026600)
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    Vidovic, Ana (6701313789)
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    Suvajdzic-Vukovic, Nada (36446767400)
    Examination of central nervous system (CNS) involvement is not routine diagnostic practice in adult patients with acute myeloid leukemia (AML). Therefore, many asymptomatic patients with CNS involvement might go undetected. The effect of CNS involvement on the AML disease course is not well defined, with conflicting results regarding clinical outcome. This study aimed to determine the incidence of asymptomatic CNS involvement in AML estimated by multiparametric flow cytometry of cerebrospinal fluid (MFC-CSF) at diagnosis, the related potential risk factors, and prognosis. In total, 645 patients with de novo AML were screened; 183 (28.4%) of them fulfilled institutional practice for MFC-CSF analysis based on presence of CNS symptoms and/or clinical features. CNS symptoms and signs were observed in 8/183 (4.4%) patients, but most patients (175/183, 95.6%) were asymptomatic. In the asymptomatic group, 73/175 (41.7%) patients had positive or suspicious cerebrospinal fluid (CSF) findings categorized as CNS positive (CNSpos) and 102/175 (58.3%) had normal CNS findings categorized as CNS negative (CNSneg). The presence of leukemic blasts was confirmed in 81/183 (44.3%) patients; the total incidence of CNS involvement in the whole AML group was 12.6% (81/645). Compared with asymptomatic patients with CNSneg, those with CNSpos had a significantly higher frequency of lymphadenopathy, white blood cell count ≥30 × 109/L, presence of the monocytic phenotype, and a high percentage of bone marrow (BM) blasts. The multivariate logistic regression model identified monocytic phenotype (p = 0.047) and high percentage of BM blasts (p = 0.042) as predictors for CNSpos. CNSpos did not affect overall survival in patients with AML. There was a higher incidence of CNS involvement in asymptomatic adult patients with de novo AML, emphasizing possible undervalued rates of CNS disease at diagnosis. Prospective studies should determine whether diagnostic lumbar puncture for MFC-CSF analysis and CNS prophylaxis could contribute to better selection and prognosis in this patient population. © 2024 John Wiley & Sons Ltd.
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