-
[show abstract]
[hide abstract]
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
-
[show abstract]
[hide abstract]
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
-
Blood Cells Molecules and Diseases 03/2012; 49(1):58-9. · 2.35 Impact Factor
-
[show abstract]
[hide abstract]
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. · 2.34 Impact Factor
-
[show abstract]
[hide abstract]
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. · 1.85 Impact Factor
-
[show abstract]
[hide abstract]
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
-
[show abstract]
[hide abstract]
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. · 2.40 Impact Factor
-
Irena Djunic, Ivo Elezovic,
Milica Marinkovic,
Nada Suvajdzic-Vukovic,
Dragica Tomin,
Gradimir Jankovic,
Jelena Bila,
Darko Antic,
Ana Vidovic,
Borka Neskovic,
Dragica Nikolic-Vukosavljevic
[show abstract]
[hide abstract]
ABSTRACT: The degradation product of collagen type I carboxy terminal telopeptide (ICTP) represents a new biochemical parameter that reflects the changes in the resorption properties of skeletal system. Affection of the skeleton is one of the most important characteristics of multiple myeloma (MM). We estimated significance of ICTP as osteolysis predictor and overall survival in comparison with standard prognostic parameters β(2)-microglobulin and C-reactive protein (CRP), in patients with MM. With our results, we have shown significant difference in serum level of ICTP (P = 0.009) between patients with and without osteolysis on conventional radiography. It was proved that ICTP is the most significant predictor of osteolysis (P = 0.09), while CRP is the most significant risk factor for overall survival (P < 0.01). Being highly significant predictor of osteolysis, ICTP can be used for identification of patients with MM who had increased risk for developing osteolytic lesions.
Medical Oncology 03/2011; 28(1):237-40. · 2.14 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Prediction of veno-occlusive disease (VOD), its precise diagnosis, and treatment have been the subject of various studies, but still remain unclear. Our goal was to investigate the levels of activated coagulation and fibrinolysis markers and natural anticoagulants in pediatric patients with VOD after hematopoietic stem cell transplantation (HSCT). We investigated 47 pediatric patients: 20 with neuroblastoma, 17 with leukemias, and 10 with lymphomas and measured the values of antithrombin (AT), protein C (PC), fibrinogen (FI), thrombin AT complex, prothrombin fragments 1+2 (F1+2), and D-dimer from day -7 to day +30 post-HSCT. Patients were monitored for the occurrence of VOD, and it occurred in 10 patients at a median post-HSCT day of 17.5 (range: 2 to 28 d). In the VOD group, at baseline the levels of FI were significantly lower, and on days +7 and +14 a relevant difference existed in F1+2 levels. The levels of PC were significantly lower on day +14. Logistic multivariate regression analysis between the groups showed significantly different D-dimer levels on day +14. On day +30, the levels of PC, AT, and F1+2 were different between these 2 groups of patients. The levels of D-dimer and F1+2 were increased, and PC and FI decreased before the clinical onset of VOD. The parameter differences may have a predictive value in VOD onset, which makes them candidates to be routinely monitored in patients after HSCT.
Journal of Pediatric Hematology/Oncology 02/2011; 33(3):227-34. · 1.16 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Myeloid sarcoma (MS) is a rare disease that presents as an extramedullary tumor of myeloid cells. Most patients subsequently develop acute myelogenous leukemia (AML), and their prognosis is poor. Here, we report the case of a 28-year-old woman with a primary isolated myeloid sarcoma which originated in the gastrointestinal (GI) tract. Two months after initial presentation, bone marrow tests led to a diagnosis of AML. This case is noteworthy because GI tract infiltration with leukemic cells is very rare, and it is even more rare as an occurrence preceding the development of systemic leukemia.
Internal Medicine 01/2010; 49(9):853-6. · 0.94 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: D-dimer testing has an important role in the exclusion of acute venous thromboembolism (VTE) in the nonpregnant population. Establishing D-dimers role in the diagnosis of VTE in pregnancy is hampered because of the substantial increase of D-dimer throughout gestational age.
In a prospective study we followed 89 healthy pregnant women to establish the reference range of D-dimer for each trimester. D-dimer testing was also performed in 12 women with clinical suspicion of VTE and their results were compared with the established new reference range of D-dimer, and with the recorded ultrasound findings.
In the first trimester, 84% women from reference group had normal D-dimer, in the second 33%, and by the third trimester only 1%, which suggests that D-dimer has no practical diagnostic use in ruling out VTE if the threshold of 230 ng/mL for abnormal is used. All pregnant women with thrombosis who had positive ultrasound findings also had statistically significant elevation of the D-dimer level, considering the established reference range of the corresponding trimester. We found 100% sensitivity of D-dimer test. A women developed thrombosis in the first trimester had 6.7-7.6 time higher level of D-dimer than the mean value in the reference group, and in the third trimester thrombotic women had 2.0-3.8 time higher level of D-dimer, p<0.0001.
D-dimer test with the new threshold for: the first of 286, the second of 457 and the third trimester of 644 ng/mL can be useful in diagnosis of pregnancy related VTE.
European journal of obstetrics, gynecology, and reproductive biology 10/2009; 148(1):27-30. · 1.97 Impact Factor
-
International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 09/2009; 107(3):250-1. · 1.41 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: It is considered that high plasma levels of procarboxypeptidase U (proCPU or TAFI) can promote the development of thrombosis, but data comparing proCPU levels in thrombophilia carriers and healthy subjects are rather scarce. Moreover, the results of previous studies on the risk of thrombosis related to high proCPU concentration in this population were not consistent. Although the 325 polymorphism of proCPU has a significant effect on the CPU half-life, it's influence on the risk of thrombosis or spontaneous pregnancy loss in carriers of hereditary thrombophilia is not clear.
The study population consisted of 144 thrombophilic patients (94 heterozygous and 10 homozygous carriers of FV Leiden, 26 heterozygous carriers of the prothrombin G20210A variation and 14 double carriers of FV Leiden and FII variation) and 69 healthy controls.
The results show that patients with inherited thrombophilia have a tendency toward lower mean proCPU plasma levels compared to healthy controls, however, this difference was only significant in carriers of FII G20210A (p=0.014). A higher frequency of the most stable Ile325Ile proCPU was seen among carriers of FII G20210A mutation compared to the control group (19% vs 7%; p=0.186). In the second part of the study proCPU as a risk factor for thrombosis was evaluated. In heterozygous carriers of FV Leiden or FII G20210A high levels of proCPU conferred to an almost 4-fold increased risk for spontaneous onset thrombosis. The more stable Ile325Ile proCPU seems to impose a higher risk for clinical manifestation of the thrombophilic condition. Finally, a significant positive correlation between F1+2 and proCPU concentration was seen.
The increased risk of thrombosis in thrombophilia patients is not only ascribable to an increased thrombin generation, but also high levels of proCPU and the presence of the 325Ile genotype tip the balance towards thrombotic tendency even further.
Thrombosis Research 03/2009; 124(4):427-32. · 2.44 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A previously healthy 24-year-old male presented with a 3-month history of progressive backache and weakness in both legs. Magnetic resonance imaging of the spine showed a large soft tissue mass infiltrating paraspinal musculature of lumbosacral area, sacral laminas, last lumbar and all sacral vertebra, protruding into the spinal canal, and with propagation into pelvis. Baseline laboratory data were normal. Decompressive laminectomy and tumor removal were performed resulting in neurological improvement. Histological examination identified granulocytic sarcoma (GS). Bone marrow biopsy showed normal findings. The patient underwent adjuvant chemotherapy and radiotherapy, resulting in the elimination of residual lesion, followed by autologous transplant. Immediate diagnosis and adequate systematic treatment are essential to achieve optimal results in patients with isolated GS. The patient is alive and free of the disease 14 months from the diagnosis.
International journal of hematology 01/2009; 89(1):95-7. · 1.17 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The absolute rate of recurrence of venous thromboembolism (VTE) is approximately 5% per year. There is a lower rate of recurrence in provoked VTE, and higher in idiopathic one. So far, there is no consensus whether hereditary thrombophilia should be considered as a persistent risk factor, and whether it requires long-term anticoagulant therapy. The aim of our study was to estimate the risk of recurrent VTE in patients carrying FV Leiden mutation in Serbian population. In retrospective study (1994-2006), we have evaluated the risk of recurrent VTE in 56 patients who are carriers of FV Leiden mutation, in comparison to group consisting of 56 patients non-carriers of FV Leiden mutation. Patients with FII G20210A and MTHFR C677T mutations, antiphospholipid antibodies, antithrombin III, protein C or protein S deficiency, malignancies and diabetes were excluded from the study. Recurrent VTE occurred in 44.6% of the patients, carriers of the FV Leiden mutations, vs. 26.7% in non-carriers group (P<0.05). The incidence rate was 3.7 and 2.2% per year, respectively. The estimated relative risk of recurrence for FV Leiden carriers was 1.67 (95% CI 0.99-2.81, P=0.049). The 60% of patients with mutation and only 13% without mutation develop rethrombosis during first year after discontinuance of therapy (P<0.01). In our study patients with symptomatic VTE who are carriers of the FV Leiden gene mutations have a higher risk of recurrent VTE than non-carriers. Our data suggest the importance of the FV Leiden mutation detection and the estimation of the clinical condition for successful secondary prophylaxis of VTE.
Journal of Thrombosis and Thrombolysis 07/2008; 25(3):284-7. · 1.48 Impact Factor
-
British Journal of Haematology 05/2008; 141(2):134. · 4.94 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Extrapelvis or retroperitoneal haemorrhage has long been appreciated as having many causes and considerable variability in subsequent morbidity; however, to date only two cases have been reported in patients with Gaucher disease, the most common lysosomal storage disorder. It had been our assumption that these cases were unique and a consequence of severe disease in patients who had not been treated with enzyme (or other disease-specific) therapy. Herein we present three more cases (as well as our first patient), which allow one to make some generalizations. Ultrasound was used in one centre and computed tomography in the second centre to make the definitive diagnosis. The trigger for the bleeding in all cases was muscle strain after activity. All patients were young with massive hepatosplenomegaly, anaemia, thrombocytopenia, and bone pain with skeletal involvement; the last was the most obvious commonality among these patients. Differential diagnosis is complicated by exquisite groin pain that is common to both Gaucher disease and extrapelvis haemorrhage, but not necessarily.
Journal of Inherited Metabolic Disease 09/2006; 29(4):593. · 3.58 Impact Factor
