I Elezović

Klinički centar Srbije, Beograd, Central Serbia, Serbia

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Publications (99)114.62 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The current widely accepted stratification defined by age and previous thrombosis in patients with essential thrombocythemia (ET) probably deserves deeper analysis. The aim of our study was to identify additional factors at the time of diagnosis, which have an impact on the thrombosis prediction. We conducted a study of 244 consecutive ET patients with median follow-up of 83 months. We analyzed the influence of age, gender, laboratory parameters, history of previous thrombosis, spleen size, JAK2 mutation as well as cardiovascular (CV) risk factors including arterial hypertension, diabetes, active tobacco use and hyperlipidemia in the terms of thrombosis. The most important predictors of thrombosis in multivariate Cox regression model were the presence of CV risk factors (p = 0.004) and previous thrombosis (p = 0.038). Accordingly, we assigned risk scores based on multivariable analysis-derived hazard ratios (HR) to the presence of 1 CV risk factor (HR = 3.5; 1 point), >1 CV risk factors (HR = 8.3; 2 points) and previous thrombosis (HR = 2.0; 1 point). A final three-tiered prognostic model for thrombosis prediction was developed as low (score 0), intermediate (score 1 or 2) and high risk (score 3) (p < 0.001). The hazard of thrombosis was 3.8 % in low-risk group, 16.7 % in the intermediate-risk group and 60 % in the high-risk group (p < 0.001). Patients with thrombotic complications during the follow-up had a significantly shorter survival (p = 0.018). The new score based on CV risk factors and previous thrombotic events allows a better patient selection within prognostic-risk groups and improved identification of the high-risk patients for thrombosis.
    Medical oncology (Northwood, London, England). 10/2014; 31(10):231.
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    ABSTRACT: Introduction Bernard-Soulier syndrome (BSS) is a rare inherited bleeding disorder characterized by giant platelets thrombocytopenia, prolonged bleeding time, frequent hemorrhages with considerable morbidity. Data on the outcome of pregnancy and gynecological intervention in BSS are rare and there are no general therapeutic recommendations.
    Srpski arhiv za celokupno lekarstvo 05/2014; 142(5-6):351-5. · 0.23 Impact Factor
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    ABSTRACT: Abstract 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 × 10(9 )cells/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.
    Platelets 04/2014; · 2.24 Impact Factor
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    ABSTRACT: Some patients with paraproteinemia have platelet aggregation disorders and the aim of this study was to examine disturbance of platelet aggregation in healthy blood donors by isolated paraprotein in vitro. Using Rivanol, paraprotein was separated from the serum of ten patients with paraproteinemia, who had decreased platelet aggregation with several inducers. Platelet aggregation in ten healthy donors was measured with and without addition of the isolated induced paraprotein. The test was repeated with added human immunoglobulins for intravenous use. Average of maximal levels of platelet aggregation has been significantly decreased in plasma rich in platelets (PRP) of healthy donors after addition of paraprotein when inducers are used: adenosine diphosphate (ADP) (P = 0.007), collagen (COL) (P = 0.008), ristocetin (RIS) (P = 0.001), and epinephrine (EPI) (P = 0.002). Average of latent time of platelet aggregation was significantly prolonged in healthy donors after addition of paraprotein with inducers: COL (P = 0.008), RIS (P = 0.008) and EPI (P = 0.006) while addition of human immunoglobulins caused no change in platelet aggregation. In comparison, when human immunoglobulins were added, maximal platelet aggregation and latent time did not change significantly. Paraprotein isolated from patients with paraproteinamia, who had decrease platelet aggregation, had significantly decreased platelet aggregation when added to PRP of healthy donors, in vitro. Platelet aggregation was not significantly changed was confirmed with addition of human immunoglobulins.
    Journal of Clinical Laboratory Analysis 01/2014; · 1.36 Impact Factor
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    ABSTRACT: The goal of this study was to compare the validity of two laboratory assays, rotation thromboelastometry (ROTEM) and endogenous thrombin potential (ETP), in monitoring and evaluating different prophylactic treatment regimens in patients with severe haemophilia.
    Clinical laboratory. 01/2014; 60(8):1325-31.
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    ABSTRACT: 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 81-131×10(9)/L) and three had additional hemostatic defects (reduced collagen platelet aggregation, FV, FXI and FXII deficiencies).
    Blood Cells Molecules and Diseases 11/2013; · 2.26 Impact Factor
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    ABSTRACT: Patients with haemophilia A have seriously impaired thrombin generation due to an inherited deficiency of factor (F)VIII, making them form unstable fibrin clots that are unable to maintain haemostasis. Data on fibrin structure in haemophilia patients remain limited. Fibrin permeability, assessed by a flow measurement technique, was investigated in plasma from 20 patients with severe haemophilia A treated on demand, before and 30 minutes after FVIII injection. The results were correlated with concentrations of fibrinogen, FVIII and thrombin-activatable fibrinolysis inhibitor (TAFI), and global haemostatic markers: endogenous thrombin potential (ETP) and overall haemostatic potential (OHP). Fibrin structure was visualized using scanning electron microscopy (SEM). The permeability coefficient Ks decreased significantly after FVIII treatment. Ks correlated significantly with FVIII levels and dosage, and with ETP, OHP and levels of TAFI. SEM images revealed irregular, porous fibrin clots composed of thick and short fibers before FVIII treatment. The clots had recovered after FVIII replacement almost to levels in control samples, revealing compact fibrin with smaller intrinsic pores. To the best of our knowledge, this is the first description of fibrin porosity and structure before and after FVIII treatment of selected haemophilia patients. It seems that thrombin generation is the main determinant of fibrin structure in haemophilic plasma.
    Thrombosis and Haemostasis 11/2013; 111(4). · 5.76 Impact Factor
  • Platelets 10/2013; · 2.24 Impact Factor
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    ABSTRACT: The study included 48 untreated patients with monoclonal gammopathies (MG). Paraprotein was isolated from the serum of 10 patients with decreased platelet aggregation. Platelet aggregation was measured before and after the addition of the isolated paraprotein to platelet-rich plasma (PRP) from 10 healthy donors, in vitro. Expression of platelet von Willebrand factor (vWF) receptor glycoprotein (GP)Ib and platelet collagen receptor GPVI was determined by flow cytometry in the PRP of healthy donors before and after the addition of isolated paraprotein using the monoclonal antibodies, CD42b (for GPIb) and CD36 (for GPVI). Flowcytometry showed that expression of CD42b and CD36 positive cells was reduced after the addition of isolated paraprotein to PRP from healthy donors (p < 0.001). These investigations demonstrated that paraprotein causes platelet dysfunction in patients with MG due to specific binding to the platelet vWF receptor GPIb and platelet collagen receptor GPVI.
    Acta Haematologica 03/2013; 130(2):101-107. · 0.89 Impact Factor
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    ABSTRACT: High-hemorrhagic early death (ED) rate is a major impediment in the managing of acute promyelocytic leukemia (APL). In our group of 56 newly diagnosed APL patients, ED occurred in 12 subjects, due to endocranial bleeding (8/12), differentiation syndrome (2/12), or infection (2/12). Predictors of hemorrhagic ED were as follows: white blood cells count ≥20 × 10(9)/L (P = 0.002337), Eastern cooperative oncology group performance status ≥3 (P = 0.00173), fibrinogen level <2 g/L (P = 0.004907), prothrombin time <50% (P = 0.0124), and International Society of Thrombosis and Hemostasis Scoring System for disseminated intravascular coagulation (ISTH DIC score) ≥6 (P = 0.00741). Multivariate analysis indicated ISTH DIC score ≥6 to be the most significant predictor for hemorrhagic ED (P = 0.008). The main finding of this study is that simple coagulation-related tests, performed on hospital admission and combined in the ISTH DIC score, might help to identify patients at high risk for fatal bleeding needing more aggressive supportive measures.
    Medical Oncology 03/2013; 30(1):478. · 2.14 Impact Factor
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    ABSTRACT: 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).
    Blood Cells Molecules and Diseases 01/2013; · 2.26 Impact Factor
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    ABSTRACT: Isolated myeloid sarcoma is an extramedullary tumor of immature myeloid cells defined by the absence of leukemia history, myelodisplastic syndrome, or myeloproliferative neoplasma with a negative bone marrow biopsy. Myeloid sarcoma is a very rare condition, and few cases have been reported. We reviewed data of 12 patients with isolated myeloid sarcoma managed at a single center to determine the possible prognostic factors affecting patient survival, such as age, sex, type, localization, and treatment options. Patients were mostly men (n=8), with a median age of 39 years. Patients were initially treated with chemotherapy (n=7) or surgery (n=5). In three patients, hematopoietic stem cell transplantation was performed. During the follow-up period, nine patients died. The median overall survival was 13 months, while event-free survival was 8 months. Regarding initial treatment strategy, no significant difference in overall survival was observed. Both chemotherapy and hematopoietic stem cell transplantation independently improved event-free survival. In addition, patients who received chemotherapy combined with hematopoietic stem cell transplantation had significantly longer event-free survival than those treated with chemotherapy alone. Age<40 years together with chemotherapy/hematopoietic stem cell transplantation significant affected event-free survival. Based on our results, the treatment of myeloid sarcoma requires a systemic rather than a localized approach with surgery or radiotherapy. While prospective evaluations are needed, chemotherapy with allogenic hematopoietic stem cell transplantation should be considered as the optimal therapy for isolated myeloid sarcoma.
    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 11/2012; · 2.24 Impact Factor
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    ABSTRACT: Haemophilia A patients with similar levels of factor VIII (FVIII) may have different bleeding phenotypes and responses to treatment with FVIII concentrate. Therefore, a test which determines overall haemostasis may be appropriate for treatment monitoring in some patients. We studied two global haemostatic methods:endogenous thrombin potential (ETP) and overall haemostatic potential(OHP) before and after injection of FVIII concentrate in patients with haemophilia A treated prophylactically and on-demand. A significant correlation between FVIII and both ETP and OHP was observed, while ETP and OHP differed between patients with severe and mild clinical phenotypes. Both ETP and OHP differed significantly between severe, moderate and mild haemophilia A and controls. ETP and OHP increased after intravenous injection of FVIII concentrate in both groups of patients, but in spite of higher pre-treatment values of both ETP and OHP in patients treated prophylactically, and much higher post-treatment FVIII levels in comparison with the values in patients treated on-demand, no difference after treatment was observed for either ETP or OHP. ETP and OHP may be additional alternatives for monitoring (and even for individual tailoring) treatment in patients with haemophilia A.
    Thrombosis and Haemostasis 04/2012; 108(1):21-31. · 5.76 Impact Factor
  • Blood Cells Molecules and Diseases 03/2012; 49(1):58-9. · 2.26 Impact Factor
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    ABSTRACT: Prognostic parameters for treatment outcome in 42 consecutive patients with t-AML diagnosed and treated in a single centre between 2000-2010 (mean age: 56.07 years, range: 23-84; 30 females) were evaluated retrospectively/prospectively. Antecedent malignancy occurred in 37 patients (88.15%): 28 solid cancers (breast, n=14), nine haematological. History of previous chemotherapy (CT), radiotherapy (RT) alone and combined CT/RT was present in 42.9%, 6.19% and 30.1% patients, respectively. Primary disease was active in 11 patients (six relapsed or metastatic cancers; five autoimmune diseases). Myelodysplastic syndrome preceded t-AML in 29% of patients. Median latency period from prior CT/RT was 54.62 months (range: 6-243). Median WBC count was 27.23 × 10⁹/L, platelet count 62.29 × 10⁹/L, haemoglobin level 87.83 g/L, peripheral blood and bone marrow blast percentage 30.7% and 66.7% respectively, serum LDH 1216 U/L. Aberrant expression of B or T lymphoid markers was registered in seven out of 39 and six out of 39 patients, respectively. Aberrant karyotype was detected in 24 out of 33 (72.7%) of eligible patients: favourable: 15.2%, intermediate: 42.4% and unfavourable: 42.4%. Eastern Cooperative Oncology Group (ECOG) performance status greater or equal to 2 and Haematopoietic Cell Transplantation Specific Comorbidity Index (HCT-CI) greater or equal to 3 exhibited 83.3% and 76.2% patients, respectively. Intensive induction CT for t-AML was administered in 24 patients. The median follow-up and the median overall survival (OS) for the whole cohort were 2 months and 5.94 months (range: 0.5-34), respectively. In 10 patients (23.8%) achieving complete remission (CR), median disease free survival (DFS) was 11.8 months (range: 4-32). Only CD19 expression, pretreatment karyotype, ECOG PS, HCT-CI and activity of primary disease had impact on OS (P<0.05).
    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 02/2012; 66(4):285-92. · 2.24 Impact Factor
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    ABSTRACT: Repeated thromboses are the most frequent clinical manifestation of antiphospholipid syndrome (APS) in the presence of antiphospholipid antibodies (aPL). The objective of this study was to observe the prevalence and localization of thrombosis, and to investigate the importance of aPL type and level for thrombosis-related events in patients diagnosed with APS. These are the first results of patients enrolled in Serbian National Cohort Study which comprises 256 patients: 162 with primary antiphospholipid syndrome (PAPS) and 94 with APS associated with systemic lupus erythematosus (SLE). aPL analysis included detection of aCL (IgG/IgM), β(2)GPI, and lupus anticoagulant. Thrombosis was diagnosed in 119 (46.5%) patients, with higher prevalence in PAPS compared with SLE patients (51.2% and 38.3%, respectively, p = 0.045). There was similar prevalence of arterial thrombosis in PAPS and SLE groups (34.6% and 34%, respectively, p = 0.932) although venous thrombosis was more frequent in PAPS (25.9% and 8.5%, respectively, p = 0.001). Thrombosis was observed in 92 (55.8%) patients who had more than one type of antibody (category I), in 13 (41.9%) patients with category IIa, in 19 (46.3%) patients with category IIb, and in 73 (44.2%) patients with category IIc (p = 0.10). The patients with thrombosis were older than those without thrombosis (49.8 and 39.8 years, respectively, p = 0.001). Overall, older age was a risk factor for thrombosis. The prevalence of venous thrombosis was higher in the PAPS group, but with lower frequency than in literature data. Any aPL type and level is a risk factor for thrombosis.
    Lupus 01/2012; 21(3):338-45. · 2.78 Impact Factor
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    ABSTRACT: Myelodysplastic syndromes (MDS) are clonal stem cell diseases that can result in cytopenias, dysplasia in one or more cell lineages, infective hematopoiesis, and increase the risk of progression to acute myeloid leukemia (AML). MDSs are characterized by several recurrent cytogenetic defects, which can affect diagnosis, prognosis, and treatment. Some of that chromosomal alterations are associated with very poor prognosis. Conventional cytogenetics cannot accurately define the rearranged karyotype. Instead, molecular cytogenetics analyses can provide important diagnostic and prognostic information for patients affected by MDS, allowing the characterization of the whole mutational spectrum and, mainly, novel chromosomal lesions. In this paper, we report a MDS case with a novel chromosomal translocation [t(17;22)(q12;q22)], described for the first time here. Following Giemsa-banding karyotyping, fluorescent in situ hybridization analyses, by using chromosome-specific probes, displayed the breakpoint regions at chromosomes 17 and 22, within which intra and inter-chromosomal segmental duplications (SD) are present. Because of the occurrence of SDs in breakpoint region, it was not possible to finely define the genomic regions where breaks fell. Further investigations could be required to better understand the molecular basis of the novel translocation t(17;22)(q12;q12) acting in MDS context and to explain if SDs could contribute to the pathogenesis of MDS.
    Gene 11/2011; 493(1):161-4. · 2.20 Impact Factor
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    ABSTRACT: 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-naïve GDPs and the effects of ERT. 31 Serbian treatment-naïve 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 5 µmol/L (ADP(5) 0.46) and collagen 5 µmol/L (Col(5) 0.47). Splenic volume inversely correlated with the platelet count and a reduced response to arachidonic acid (AA), Col(5) and ADP(5) (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 ERT(0) to ERT(24) (PT(0) 65%, PT(24) 81%; p < 0.05). The von Willebrand factor had increased significantly by ERT(6) and ERT(24) (ERT(0) 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: ERT(0) 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.
    Platelets 07/2011; 23(2):143-9. · 2.24 Impact Factor
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    ABSTRACT: We investigated molecular and biological parameters reflecting the biology of chronic lymphocytic leukemia (CLL) that may help us to predict the time to first treatment (TTT). A group of 33 patients with newly diagnosed CLL (Binet stage A) were analyzed. We developed a new scoring system based on the serum levels of β(2)-microglobulin (β(2)M) and vascular endothelial growth factor (VEGF) and the expression of lipoprotein lipase (LPL). Patients with a score of 0 had a TTT of 58.4 months, while patients with a score of 3 (increased levels of β(2)M, LPL, and VEGF) had a significantly shorter TTT of only 10.6 months (p < 0.0001).
    Leukemia & lymphoma 07/2011; 52(7):1394-7. · 2.61 Impact Factor
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    ABSTRACT: Acquired von Willebrand syndrome (AvWS) is an uncommon complication of multiple myeloma (MM), and it is believed to be connected with paraprotein. The aim of this study was to determine the incidence of AvWS in patients with MM, and estimate the role of paraprotein in its occurrence. The study included 40 patients with MM. The plasma level of paraprotein, platelet adhesion on glass pearls, plasma von Willebrand factor antigen concentration, and ristocetin-induced platelet aggregation (RIPA) were measured initially. Absence of RIPA was found in six patients with MM (15%); however, all six of them had normal levels of von Willebrand factor antigen. Paraprotein was isolated from the serum of these patients. Platelet aggregation was measured in six healthy donors before and after addition of the isolated paraprotein. RIPA was significantly decreased in healthy donors in the presence of paraprotein (P<0·001). The same test was repeated with added human immunoglobulins for intravenous use without any change in RIPA. A significant negative correlation between plasma paraprotein level and RIPA was found (P<0·001). These investigations have shown that paraprotein is associated with AvWS in patients with MM.
    Hematology (Amsterdam, Netherlands) 07/2011; 16(4):209-12. · 1.33 Impact Factor

Publication Stats

190 Citations
114.62 Total Impact Points


  • 1998–2014
    • Klinički centar Srbije
      • • Institute of Haematology
      • • Clinical Center of Serbia
      Beograd, Central Serbia, Serbia
  • 1989–2012
    • University of Belgrade
      Beograd, Central Serbia, Serbia
  • 2010–2011
    • Institut za zdravstvenu zaštitu majke i deteta Srbije Dr Vukan Čupić
      Beograd, Central Serbia, Serbia
  • 2008–2010
    • Institut za transfuziju krvi Srbije
      Beograd, Central Serbia, Serbia