Browsing by Author "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.

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.

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.

Clinical features of 40 lymphoproliferative neoplasm patients in the setting of systemic autoimmune diseases managed in the Clinic of Hematology during 1994-2006 were analyzed retrospectively. The classification of systemic autoimmune disease patients was as follows: 15 systemic lupus erythematosus-SLE, 11 rheumatoid arthritis-RA, 12 Sjögren's syndrome-SS, 1 scleroderma, and 1 dermatomyositis. Patients comprised 31 women and 9 men of mean age 55 years (range 33-76). Systemic autoimmune diseases preceeded the development of lymphoproliferative neoplasms in 37/40 (92.5%) patients. Mean latency period between the onset of systemic autoimmune diseases and lymphoproliferative neoplasms occurrence was significantly longer in RA (113 months) than in SLE (75 months) and SS patients (65 months)-P < 0.05. The most frequent lymphoproliferative neoplasms were non-Hodgkin's lymphoma-NHL (35/40; 88%), diffuse large B-cell lymphoma (DBCL)-12 (34%), follicular lymphoma (FC)-7 (20%), small lymphocytic (SL), and marginal zone lymphoma (MZL)-5 (14%) each. The primary site of NHL was extranodal in 18/35 (51.5%) cases. Advanced disease on diagnosis (III + IV clinical stages), constitutional symptoms, and bulky disease were diagnosed in 27/35 (77%), 26/35 (74%), and 3/35 (8.5%) patients, respectively. The overall survival (OS) was as follows (months): DBCL-12, FC-63, SLL-60, and MZL-48. There was no association between the lymphoproliferative neoplasm histological subtype and the systemic autoimmune diseases type or antirheumatic treatment P > 0.05. Our findings are in line with earlier reports showing a high proportion of patients with advanced disease, constitutional symptoms, extranodal manifestations, high grade histology, and low OS in the systemic autoimmune diseases setting. Copyright © Springer Science+Business Media, LLC 2011.

Clinical features of 40 lymphoproliferative neoplasm patients in the setting of systemic autoimmune diseases managed in the Clinic of Hematology during 1994-2006 were analyzed retrospectively. The classification of systemic autoimmune disease patients was as follows: 15 systemic lupus erythematosus-SLE, 11 rheumatoid arthritis-RA, 12 Sjögren's syndrome-SS, 1 scleroderma, and 1 dermatomyositis. Patients comprised 31 women and 9 men of mean age 55 years (range 33-76). Systemic autoimmune diseases preceeded the development of lymphoproliferative neoplasms in 37/40 (92.5%) patients. Mean latency period between the onset of systemic autoimmune diseases and lymphoproliferative neoplasms occurrence was significantly longer in RA (113 months) than in SLE (75 months) and SS patients (65 months)-P < 0.05. The most frequent lymphoproliferative neoplasms were non-Hodgkin's lymphoma-NHL (35/40; 88%), diffuse large B-cell lymphoma (DBCL)-12 (34%), follicular lymphoma (FC)-7 (20%), small lymphocytic (SL), and marginal zone lymphoma (MZL)-5 (14%) each. The primary site of NHL was extranodal in 18/35 (51.5%) cases. Advanced disease on diagnosis (III + IV clinical stages), constitutional symptoms, and bulky disease were diagnosed in 27/35 (77%), 26/35 (74%), and 3/35 (8.5%) patients, respectively. The overall survival (OS) was as follows (months): DBCL-12, FC-63, SLL-60, and MZL-48. There was no association between the lymphoproliferative neoplasm histological subtype and the systemic autoimmune diseases type or antirheumatic treatment P > 0.05. Our findings are in line with earlier reports showing a high proportion of patients with advanced disease, constitutional symptoms, extranodal manifestations, high grade histology, and low OS in the systemic autoimmune diseases setting. Copyright © Springer Science+Business Media, LLC 2011.

The study aimed to identify genetic lesions associated with secondary acute myeloid leukemia (sAML) in comparison with AML arising de novo (dnAML) and assess their impact on patients' overall survival (OS). High-resolution genotyping and loss of heterozygosity mapping was performed on DNA samples from 86 sAML and 117 dnAML patients, using Affymetrix Genome-Wide Human SNP 6.0 arrays. Genes TP53, RUNX1, CBL, IDH1/2, NRAS, NPM1, and FLT3 were analyzed for mutations in all patients. We identified 36 recurrent cytogenetic aberrations (more than five events). Mutations in TP53, 9pUPD, and del7q (targeting CUX1 locus) were significantly associated with sAML, while NPM1 and FLT3 mutations associated with dnAML. Patients with sAML carrying TP53 mutations demonstrated lower 1-year OS rate than those with wild-type TP53 (14.3% ± 9.4% vs. 35.4% ± 7.2%; P = 0.002), while complex karyotype, del7q (CUX1) and del7p (IKZF1) showed no significant effect on OS. Multivariate analysis confirmed that mutant TP53 was the only independent adverse prognostic factor for OS in sAML (hazard ratio 2.67; 95% CI: 1.33-5.37; P = 0.006). Patients with dnAML and complex karyotype carried sAML-associated defects (TP53 defects in 54.5%, deletions targeting FOXP1 and ETV6 loci in 45.4% of the cases). We identified several co-occurring lesions associated with either sAML or dnAML diagnosis. Our data suggest that distinct genetic lesions drive leukemogenesis in sAML. High karyotype complexity of sAML patients does not influence OS. Somatic mutations in TP53 are the only independent adverse prognostic factor in sAML. Patients with dnAML and complex karyotype show genetic features associated with sAML and myeloproliferative neoplasms. © 2012 Wiley Periodicals, Inc.

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.

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.

A retrospective survey of 210 consecutive patients aged ≥65 years (median age 69 years, range 65- 88 years) with acute myeloid leukemia (AML) diagnosed at a single center over a 6-year period (January 2001 to December 2006) is presented. De novo AML was diagnosed in 179 (85.2 %) patients and 31 (14.7 %) patients had a secondary AML. Twenty-three patients had M0 (11 %), 36 M1 (17.15 %), 57 M2 (27.1 %), eight M3 (3.8 %), 45 M4 (21.4 %), 31 M5 (14.8 %), one M6 (0.5 %), one M7 (0.5 %), and eight patients had unclassified myeloid leukemia (3.8 %) according to French-American-British (FAB) Study Group Classification. Eight patients with M3 (acute promyelocytic leukemia) were excluded from the study. Cytogenetic analysis was performed in 172/202 (85 %) patients. The normal karyotype was found in 81/ 172 (47 %), high risk aberrations in 32/172 (18.6 %), and favorable karyotype in 13/172 (7.5 %) patients. Supportive and palliative therapies were applied in 115 (56.9 %) patients, a no induction chemotherapy (NIC) group, and 87 (43.1 %) patients received induction chemotherapy (IC group). Complete remission (CR) was achieved in 45/87 (51.7 %) in the IC group and in 5/115 (4.3 %) in the NIC group of patients. After a median follow up of 4 years, 194 (96 %) patients died. The variables significantly associated with a longer overall survival (OS) by univariate analysis were an age of <75 years, a better ECOG performance status (PS) (p00.000, CI 95.0 %, 1.358-2.049), a serum LDH activity <600 U/l (p00.000, CI 95.0 %, 1.465-2.946), lower white blood cell (WBC) count at diagnosis (p00.011, CI 95.0 %, 1.102-2.100), lower comorbidity HCT-CI index (p00.000, CI 95 % 2.209-3.458), absence of splenomegaly (p00.015, CI 95.0 %, 1.082-2.102) and hepatomegaly (p0 0.008, CI 95.0 %, 1.125-2.171), and no preceding nonhematological malignancy. Multivariate analysis showed that significant factors affecting OS in the IC group were achievement of CR (p00.000), the ECOG PS (p00.045) and the ECOG PS (p00.000), and HCT-CI (p00.000) in the NIC group of elderly patients. The present study suggests that a subgroup of elderly patients with both ECOG PS and HCT-CI≤2 at presentation may be eligible for intensive induction chemotherapy. © 2012 Springer-Verlag.

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. © 2013 Springer Science+Business Media New York.

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. © 2013 Springer Science+Business Media New York.

[No abstract available]

[No abstract available]

We evaluated coagulation abnormalities via traditional tests and rotational thromboelastometry (ROTEM) in a group of 94 patients with confirmed SARS-CoV-2 infection and different severity of pneumonia (34 moderate, 25 severe, 35 critical) with the hypothesis that ROTEM parameters differed by coronavirus disease 2019 (COVID-19) severity. Shorter than normal clotting time (CT) and higher than normal maximum clot firmness (MCF) in extrinsic rotational thromboelastometry (EXTEM) and fibrinogen rotational thromboelastometry (FIBTEM), shorter than normal EXTEM clot formation time (CFT), and higher than normal α-angle were classified as markers of hypercoagulable state. Increment in the number of patients with ≥2 hypercoagulable parameters, higher EXTEM (P =.0001), FIBTEM MCF (P =.0001) and maximum lysis decrement (P =.002) with increment in disease severity was observed (P =.0001). Significant positive correlations between IL6 and CT EXTEM (P =.003), MCF EXTEM (P =.033), MCF FIBTEM (P =.01), and negative with ML EXTEM (P =.006) were seen. Our findings based on analysis of different disease severity groups confirmed that a hypercoagulable ROTEM pattern characterized by clot formation acceleration, high clot strength, and reduced fibrinolysis was more frequent in advanced disease groups and patients with high IL6. These results supported the need for different thromboprophylaxis approaches for different severity groups. © 2021 Taylor & Francis Group, LLC.

Introduction Thrombotic events (TE) appear to be more common in acute promyelocytic leukemia (APL) than in other acute leukemias, with reported prevalence ranging from 2 to10-15%. Materials and Methods We retrospectively analyzed the data on TE appearance in 63 APL patients. Results TE occured in 13 (20.6%) cases, four arterial (6.3%) and nine venous (14.3%). TE were more frequently diagnosed after initiation of weekly D-dimer monitoring (7 TE during 20 months vs 6 during 76 months, P = 0.032). Patients with and without venous thrombosis were significantly different regarding female/male ratio (P = 0.046), PT (P = 0.022), aPTT (P = 0.044), ISTH DIC score (P = 0.001), bcr3 (P = 0.02) and FLT3-ITD (P = 0.028) mutation. The most significant risk factor for venous TE occurrence in multivariate analysis was FLT3-ITD mutation (P = 0.034). PAI-1 4G/4G polymorphism was five times more frequent in patients with venous TE than without it (P = 0.05). Regarding risk factors for arterial TE we failed to identify any. Conclusions We have demonstrated that APL-related TE rate is higher than previously reported and that weekly D-dimer monitoring might help to identify patients with silent thrombosis. Moreover, our study suggests a possible relationship between venous TE occurrence and several laboratory findings (PT, aPTT, ISTH DIC score, bcr3 isoform, FLT3-ITD mutation and PAI 4G/4G). Prophylactic use of heparin might be considered in patients with ISTH DIC score < 5, bcr3 isoform, FLT3-ITD mutation and PAI 4G/4G. © 2014 Elsevier Ltd.

We present two cases of acute myeloid leukemia (AML) who developed Varicella-Zoster Virus (VZV) encephalitis after completion of standard "3 + 7" induction remission chemotherapy. A 50-year-old patient developed disseminated cutaneous Herpes Zoster (HZ) 2 days after completion of induction chemotherapy for AML. The patient was treated with intravenous acyclovir 7 days and then orally. On the second day following intravenous acyclovir discontinuation confusion, cerebelar ataxia somnolescence and VZV encephalitis was diagnosed. The other 38-year-old patient developed neuroleukemia and VZV encephalitis without skin rash after completion of induction chemotherapy. In both patients the diagnosis was confirmed by polymerase chain reaction (PCR) for VZV DNA in serum and liquor. The first patient completely recovered after reinstitution of intravenous acyclovir while the other patient a month later. This is unusual presentation of VZV encephalitis occurring in a patient with AML after standard induction remission chemotherapy which implies the significance of early diagnosis and screening for viral infections in AML patients with unusual neurologic presentation even in absence of rash. The screening for viral infections should be performed because antiviral prophylaxis is not routinely recommended for AML during standard induction chemotherapy by most clinical guidelines. © 2013 Elsevier Masson SAS.

We present two cases of acute myeloid leukemia (AML) who developed Varicella-Zoster Virus (VZV) encephalitis after completion of standard "3 + 7" induction remission chemotherapy. A 50-year-old patient developed disseminated cutaneous Herpes Zoster (HZ) 2 days after completion of induction chemotherapy for AML. The patient was treated with intravenous acyclovir 7 days and then orally. On the second day following intravenous acyclovir discontinuation confusion, cerebelar ataxia somnolescence and VZV encephalitis was diagnosed. The other 38-year-old patient developed neuroleukemia and VZV encephalitis without skin rash after completion of induction chemotherapy. In both patients the diagnosis was confirmed by polymerase chain reaction (PCR) for VZV DNA in serum and liquor. The first patient completely recovered after reinstitution of intravenous acyclovir while the other patient a month later. This is unusual presentation of VZV encephalitis occurring in a patient with AML after standard induction remission chemotherapy which implies the significance of early diagnosis and screening for viral infections in AML patients with unusual neurologic presentation even in absence of rash. The screening for viral infections should be performed because antiviral prophylaxis is not routinely recommended for AML during standard induction chemotherapy by most clinical guidelines. © 2013 Elsevier Masson SAS.