Publications by authors named "Minodora Onisâi"

23 Publications

  • Page 1 of 1

The Impact of Increased Fib-4 Score in Patients with Type II Diabetes Mellitus on Covid-19 Disease Prognosis.

Medicina (Kaunas) 2021 Apr 30;57(5). Epub 2021 Apr 30.

Gastroenterology Department, Emergency University Hospital of Bucharest, "Carol Davila" University of Medicine and Pharmacy, 050098 Bucharest, Romania.

Emerging evidence suggests that patients with metabolic (dysfunction) associated fatty liver disease (MAFLD) are prone to severe forms of coronavirus disease (COVID-19), especially those with underlying liver fibrosis. The aim of our study is to assess the association of an increased FIB-4 score with COVID-19 disease prognosis. We performed a prospective study on hospitalized patients with known type II diabetes mellitus (T2DM) and confirmed COVID-19, with imaging evidence of liver steatosis within the last year or known diagnosis of MAFLD. All individuals were screened for liver fibrosis with a FIB-4 index. We evaluated the link between FIB-4 and disease prognosis. Of 138 participants, 91.3% had MAFLD and 21.5% patients had a high risk of fibrosis. In the latter group of patients, the number of severe forms of disease, the hospital stay length, the rate of ICU admissions and the number of deaths reported registered a statistically significant increase. The independent predictors for developing severe forms of COVID-19 were obesity (odds ratio (OR), 3.24; 95% confidence interval (CI), = 0.003), higher values of ferritin (OR-1.9; 95% CI, 1.17-8.29, = 0.031) and of FIB-4 ≥ 3.25 (OR-4.89; 95% CI, 1.34-12.3, = 0.02). Patients with high scores of FIB-4 have poor clinical outcomes and liver fibrosis may have a relevant prognostic role. Although the link between liver fibrosis and the prognosis of COVD-19 needs to be evaluated in further studies, screening for liver fibrosis with FIB-4 index, particularly in patients at risk, such as those with T2DM, will make a huge contribution to patient risk stratification.
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http://dx.doi.org/10.3390/medicina57050434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147130PMC
April 2021

Effects of Ibrutinib on biophysical parameters of platelet in patients with chronic lymphocytic leukaemia.

Am J Blood Res 2020 15;10(6):311-319. Epub 2020 Dec 15.

Biophysics and Cellular Biotechnology Department, Carol Davila University of Medicine and Pharmacy 8 Eroii Sanitari Boulevard, Bucharest 050474, Romania.

Patients with chronic lymphocytic leukemia (CLL) treated with Ibrutinib often present hemorrhagic complications. Platelets dysfunction is well documented by aggregometry and flow cytometry, but the mechanisms by which Ibrutinib treatment influences the platelets status is yet to be evaluated. The aim of this study is to identify platelet membrane parameters in chronic lymphocytic leukemia (CLL) that could be altered by Ibrutinib administration. In this paper we propose a set of fluorescence measurements of the following parameters: membrane fluidity, resting membrane potential, and reactive oxygen species production of platelets suspensions obtained from CLL patients treated or not with Ibrutinib as markers for platelets status in this pathological situation. Platelets from CLL patients treated with Ibrutinib have higher membrane fluidity, lower resting membrane potential and higher level of reactive oxygen species production compared to the untreated CLL patients. These patients are also presenting higher membrane fluidity and lower resting membrane potential compared to healthy volunteers.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811905PMC
December 2020

Effects of Exogenous Androgens on Platelet Activity and Their Thrombogenic Potential in Supraphysiological Administration: A Literature Review.

J Clin Med 2021 Jan 4;10(1). Epub 2021 Jan 4.

Division of Physiology and Neuroscience, Department of Functional Sciences, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania.

Anabolic androgenic steroids (AAS), simply called "androgens", represent the most widespread drugs used to enhance performance and appearance in a sporting environment. High-dosage and/or long-term AAS administration has been associated frequently with significant alterations in the cardiovascular system, some of these with severe endpoints. The induction of a prothrombotic state is probably the most life-threatening consequence, suggested by numerous case reports in AAS-abusing athletes, and by a considerable number of human and animal studies assessing the influence of exogenous androgens on hemostasis. Despite over fifty years of research, data regarding the thrombogenic potential of exogenous androgens are still scarce. The main reason is the limited possibility of conducting human prospective studies. However, human observational studies conducted in athletes or patients, in vitro human studies, and animal experiments have pointed out that androgens in supraphysiological doses induce enhanced platelet activity and thrombopoiesis, leading to increased platelet aggregation. If this tendency overlaps previously existing coagulation and/or fibrinolysis dysfunctions, it may lead to a thrombotic diathesis, which could explain the multitude of thromboembolic events reported in the AAS-abusing population. The influence of androgen excess on the platelet activity and fluid-coagulant balance remains a subject of debate, urging for supplementary studies in order to clarify the effects on hemostasis, and to provide new compelling evidence for their claimed thrombogenic potential.
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http://dx.doi.org/10.3390/jcm10010147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795962PMC
January 2021

Synchronous Multiple Breast Cancers-Do We Need to Reshape Staging?

Medicina (Kaunas) 2020 May 11;56(5). Epub 2020 May 11.

Faculty of General Medicine, University of Medicine and Pharmacy Carol Davila Bucharest, 050474 Bucharest, Romania.

Current recommendations and treatment regimens in breast cancer are a reflection of its heterogeneity on multiple levels including histological subtypes, grading, molecular profiling, and numerous prognostic indices. Although based on extensive research, current guidelines are not explicit in the case of surgical specimens showing various degrees of mismatch between different parts of the same tumor and even more so between multicentric lesions. Synchronous breast cancer is the ideal prototype for studying inter- and intra-tumoral heterogeneity, therefore we envisaged that a study on patients with multicentric and multifocal lesions could contribute to the reshaping of the staging, prognosis, and treatment of breast malignancies. A prospective observational study was conducted between January 2013 and May 2017 on 235 patients diagnosed with breast cancer (BC) and surgically treated at Emergency University Hospital, Bucharest. Thirty-seven patients had multiple breast tumors and were eligible for assessment of the heterogeneity of their lesions. : 6 were multicentric and 31 multifocal. The number of foci varied from 2 to 11. We encountered numerous mismatches between the index and the secondary tumors, as follows: 3 cases (8.1%) with histopathological mismatch, 13 (35.1%) with different grades of differentiation, 11 (29.8%) with ER (Estrogen Receptors) status mismatch, 12 (32.4%) with PR (Progesterone Receptors) status mismatch, 8 (21.6%) with molecular phenotype mismatch, and 17 (45.9%) cases with variable Ki-67. After careful analysis of index and secondary tumors, apart from the mismatches reported above, we discovered that the secondary tumors were actually dominant in 5 cases (13.5%), and therefore at least those cases had to be reclassified/restaged, as the supplementary data commanded changes in the therapeutic decision. For synchronous breast tumors, the current Tumor-Node-Metastasis (TNM) staging system ignores not only the histopathological and immunohistochemical characteristics of the secondary foci, but also their size. When secondary lesions are more aggressive or their cumulative mass is significantly bigger than that of the index tumor, the treatment plan should be adapted accordingly. We believe that information obtained from examining secondary foci in synchronous breast cancer and assessment of the cumulative tumoral mass should be reflected in the final staging and definitive treatment. The clinical benefit of staging the patients based on the most aggressive tumor and the cumulative tumoral burden rather than according to the biggest single tumor, will avoid under-treatment in cases with multifocal/multicentric BC displaying intertumoral mismatch.
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http://dx.doi.org/10.3390/medicina56050230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279247PMC
May 2020

Splenectomy in Lymphoproliferative Disorders: A Single Eastern European Center Experience.

Medicina (Kaunas) 2019 Dec 27;56(1). Epub 2019 Dec 27.

Faculty of General Medicine, University of Medicine and Pharmacy Carol Davila Bucharest, 050474 Bucharest, Romania.

Hematological malignancies are usually systemic diseases of life-threatening impact, and frequently require prompt and energetic therapeutic intervention. Due to systemic involvement, the role of surgery is generally limited to diagnostic approaches, and it is very rarely employed as a therapeutic modality. Splenectomy represents an exception to this paradigm, being used both as a diagnostic and tumor debulking procedure, notably in splenic lymphomas. We investigated the role of splenectomy in a single center prospective study of splenectomy outcome in patients with splenic involvement in the course of lymphoproliferative disorders. In the present study, we included all patients treated in our department for lymphoid malignancies over a period of six years, who underwent splenectomy as a diagnostic or debulking procedure after referral and workup, or had been referred to our department after first being splenectomized and diagnosed with splenic lymphoma. Patient characteristics and treatment outcome were investigated. : We enrolled 54 patients, with 34 (63%) splenectomized patients: 12 splenectomies (22.2%) for diagnostic purposes and 22 (40.7%) for treatment. Special attention was given to the 28 (51.85%) patients diagnosed with splenic marginal zone lymphoma (SMZL), a subtype with a clear therapeutic indication for splenectomy. Average age of patients was 57.5 (±13.1) years with a higher prevalence of feminine gender (66.67%). Age above 60 years old ( = 0.0295), ECOG (Eastern Cooperative Oncology Group) > 2 ( = 0.0402) and B-signs ( nonsignificant (NS)) were most frequently found in SMZL patients. Anemia, and notably autoimmune anemia, was more frequent in SMZL versus other small-cell lymphomas and also in splenectomized patients, as was leukocytosis and lymphocytosis. Treatment of patients with lymphoproliferative disorders consisted of chemotherapy and/or splenectomy. Most SMZL patients received chemotherapy as first line treatment (61.5%) and had only partial response (57.7%). Second treatment line was splenectomy in 80% of patients who required treatment, followed by a 60% rate of complete response (CR). Splenectomy offered a higher complete response rate (twice as high than in non-splenectomized, regardless of histology type, = NS), followed by a survival advantage (Overall Survival (OS)~64 versus 59 months, = NS). Particularly, SMZL patients had a 4.8 times higher rate of CR than other non-Hodgkin lymphoma (NHL) patients ( = 0.04), a longer progression free survival (73 months vs. 31 months for other small-cell NHLs = NS) and a 1.5fold lower death rate ( = NS). The procedure was rather safe, with a 38.5% frequency of adverse reactions, mostly minor and manageable. Our data suggest that splenectomy is an effective and safe therapeutic option in patients with lymphoid malignancies and splenic involvement, particularly splenic marginal zone lymphoma.
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http://dx.doi.org/10.3390/medicina56010012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7022624PMC
December 2019

Idiopathic thrombocytopenic purpura (ITP) - new era for an old disease.

Rom J Intern Med 2019 Dec;57(4):273-283

Hematology Clinic, Emergency University Hospital, Bucharest, Romania.

Immune thrombocytopenia is an autoimmune hematological disorder characterized by severely decreased platelet count of peripheral cause: platelet destruction via antiplatelet antibodies which may also affect marrow megakaryocytes. Patients may present in critical situations, with cutaneous and/or mucous bleeding and possibly life-threatening organ hemorrhages (cerebral, digestive, etc.) Therefore, rapid diagnosis and therapeutic intervention are mandatory. Corticotherapy represents the first treatment option, but as in any autoimmune disorder, there is a high risk of relapse. Second line therapy options include: intravenous immunoglobulins, thrombopoietin receptor agonists, rituximab or immunosuppression, but their benefit is usually temporary. Moreover, the disease generally affects young people who need repeated and prolonged treatment and hospitalization and therefore, it is preferred to choose a long term effect therapy. Splenectomy - removal of the site of platelet destruction - represents an effective and stable treatment, with 70-80% response rate and low complications incidence. A challenging situation is the association of ITP with pregnancy, which further increases the risk due to the immunodeficiency of pregnancy, major dangers of bleeding, vital risks for mother and fetus, potential risks of medication, necessity of prompt intervention in the setting of specific obstetrical situations - delivery, pregnancy loss, obstetrical complications, etc. We present an updated review of the current clinical and laboratory data, as well as a detailed analysis of the available therapeutic options with their benefits and risks, and also particular associations (pregnancy, relapsed and refractory disease, emergency treatment).
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http://dx.doi.org/10.2478/rjim-2019-0014DOI Listing
December 2019

POEMS syndrome complicated with multiple ischemic vascular events: case report and review of literature.

Onco Targets Ther 2018 27;11:6271-6276. Epub 2018 Sep 27.

Department of Hematology, University Emergency Hospital Bucharest, Bucharest, Romania,

POEMS syndrome (acronym consisting of: polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) is an uncommon disorder associated with an underlying plasma cell dyscrasia. There is no single specific test for POEMS, and due to its rarity and heterogeneity, patients are often mis- or underdiagnosed. Castleman disease (CD) is a rare lymphoproliferative disorder, closely related to POEMS syndrome; ~11%-30% of POEMS patients are associated with concomitant CD. In contrast to frequently published reports on vascular events in POEMS syndrome affecting coronary arteries or lower limbs, cases of cerebrovascular events are rarely mentioned in literature. We hereby report a patient with POEMS syndrome accompanied by CD who presented recurrent strokes and splenic infarction.
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http://dx.doi.org/10.2147/OTT.S146221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6166759PMC
September 2018

A Challenging Case of Kikuchi-Fujimoto Disease Associated with Systemic Lupus Erythematosus and Review of the Literature.

Case Rep Hematol 2018 23;2018:1791627. Epub 2018 Jan 23.

Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.

Kikuchi-Fujimoto disease (KFD) or histiocytic necrotizing lymphadenitis is a rare disease that is frequently underdiagnosed due to clinical features that are similar to those of non-Hodgkin lymphomas, systemic lupus erythematosus (SLE), or infectious reactive lymphadenopathy. An excisional biopsy is required. We report a young Caucasian female diagnosed with KFD with skin lesions, complicating with SLE. The clinical course, laboratory, and CT findings are described, as are histopathologic features, for a better recognition of this rare disorder in clinical practice.
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http://dx.doi.org/10.1155/2018/1791627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5896377PMC
January 2018

Early severe preeclampsia with marked platelet dysfunction in association with essential thrombocytemia: case report and discussion.

Blood Coagul Fibrinolysis 2015 Oct;26(7):830-3

aHematology Department, University Emergency Hospital Bucharest bObstetrics-Gynecology Department, Elias University Emergency Hospital cHematology Department, Colentina Hospital, Bucharest, Romania.

Essential thrombocytemia--a classic myeloproliferative neoplasm characterized by persistent thrombocytosis--may associate both thrombotic and hemorrhagic events, as well as platelet dysfunction. Of all myeloproliferative neoplasms, essential thrombocytemia is more likely to be associated with pregnancy, because of a higher comparative incidence in younger patients. This association significantly increases the risk of pregnancy loss and of various pregnancy complications. We present a case of early severe preeclampsia with a critical and unusual evolution and life-threatening complications.
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http://dx.doi.org/10.1097/MBC.0000000000000352DOI Listing
October 2015

Therapeutic Options for Immune Thrombocytopenia (ITP) During Pregnancy.

Maedica (Bucur) 2013 Jun;8(2):182-8

Elias Emergency University Hospital, Department of Obstetrics-Gynecology, Bucharest, Romania.

Abstract: The incidence of ITP during pregnancy is low. When ITP is suspected it is necessary to perform an extended set of clinical and biological investigations in order to determine the etiology of thrombocytopenia, as the diagnosis of ITP is a process of exclusion, because there is no sensitive and specific diagnostic test so far. The treatment for ITP during pregnancy represents a challenge, being necessary in the cases selected according to the obstetrical indications, to the degree of maternal thrombocytopenia and to the extent of the hemorrhagic syndrome, as well as according to the adverse reactions of the treatment on the mother and fetus.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3865128PMC
June 2013

Assessment of changes in membrane properties of platelets from patients with chronic myeloid leukaemia in different stages of the disease.

Blood Coagul Fibrinolysis 2014 Mar;25(2):142-50

aDepartment of Hematology, Emergency University Hospital, Bucharest bDepartment of Hematology, County Emergency Hospital Arges, Pitesti cDepartment of Biophysics and Cell Biotechnology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.

Patients with chronic myeloproliferative leukemia (CML) have frequent haemorrhage and/or thrombosis in their medical history. The mechanisms of these major and life-threatening complications remain unclear. Membrane organization influences many of the unique cellular functions and is strongly correlated, among other factors, to the membrane lipid composition; it may be evaluated by following up the membrane fluidity and aggregation properties of the platelet. In this study, we evaluated the platelet aggregation, the expression of platelet surface receptors, the membrane fluidity (as evaluated by fluorescence anisotropy) and its correlation to reactive oxygen species (ROS) production, in patients with chronic myeloid leukaemia (CML). It was found that the patients in accelerated and blastic phase of CML present an altered platelet aggregation response to all reagents except for ristocetin as compared with chronic phase group, which shows only epinephrine-altered response. We also found that BCR/ABL transcript leads to higher levels of ROS in accelerated and blastic CML phases. Patients without molecular remission have lower platelet membrane fluidity. We obtained a positive correlation between ROS level and membrane fluorescence anisotropy changes. The CD41 expression was decreased in CML patients and P selectin expression was found to be higher in these patients than in healthy volunteers. Platelets of CML patients have altered aggregation parameters in accelerated and blastic phases, in which BCR/ABL transcript level is increased. The increased level of ROS in CML patients without molecular remission is associated with a decrease in fluidity of platelet membrane and expression of CD41/CD61 receptors. These findings may contribute to understanding the mechanism of the altered platelet response reported in CML patients.
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http://dx.doi.org/10.1097/MBC.0b013e328365776fDOI Listing
March 2014

Favorable outcome under anticoagulant therapy in a high risk pregnancy case report and short review of the (recent) literature.

Maedica (Bucur) 2012 Dec;7(4):339-43

Department of Hematology, Emergency University Hospital, Bucharest, Romania.

The incidence of venous thromboembolism is significantly increased during pregnancy, recurrent venous thromboembolism being a serious complication because it is potentially life-threatening. According to recent ACCP guidelines, women with "high-risk" thrombophilias (e.g., homozygosity for factor V Leiden) who had a single prior episode of VTE treated with oral anticoagulants, should receive LMWH or UFH during pregnancy and puerperium, followed by resumption of long-term anticoagulants postpartum.We present the case of a young woman with a history of severe deep vein thrombosis of the inferior vena cava, occurring during oral contraceptive use. Subsequent investigation revealed homozygosity for Leiden mutation. She was treated with enoxaparin throughout gestation and 6 weeks postpartum and no complications appeared.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3593286PMC
December 2012

Refractory anemia with ring sideroblasts associated with marked thrombocytosis: case report and literature review.

Rom J Morphol Embryol 2012 ;53(3):645-50

Department of Hematology, Emergency University Hospital, Bucharest, Romania.

"Refractory anemia with ring sideroblasts and thrombocytosis" (RARS-T) is a rare disease, a provisional entity, with a controversial status in the 2008 revised WHO classification. Even at present time, RARS-T is a matter of debate whether it is a distinct clinicopathological entity or more likely a constellation of clinical and pathological features of two well-defined myeloid neoplasms, myelodysplastic syndrome and myeloproliferative neoplasm. Perhaps none of the clonal disorders illustrates better the challenges presented by the current classification of myeloid neoplasms, than this clinical entity with overlapping features of both refractory anemia with ring sideroblasts and essential thrombocythemia. The purpose of this study is to present the evolution of such a case, with difficulties in establishing not only the correct diagnosis, but also the appropriate therapeutic approach. For this reported case, we present documented details regarding persistent thrombocytosis, slightly increased number of leukocytes and analysis of Janus kinase 2 (JAK2) genes that revealed a V617F mutation, confirming the presence of an underlying myeloproliferative neoplasm, followed later in the evolution by occurrence of myelodysplastic features as ring sideroblasts. This case might interest pathologists, but especially clinicians, for at least two reasons: the rarity of this disease and the lack of data on prognosis of these patients, probably because of relatively recent established diagnosis criteria and existence of few studies with small number of patients. The third interesting aspect for practitioners would be the absence of consensus on optimal clinical treatment for this disorder, because there are few cases that meet the rigorous diagnostic criteria.
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April 2013

Double transformation of a hematopoietic malignancy and severe associated thrombopathy. Case presentation and review of the literature.

Rom J Intern Med 2011 ;49(2):137-44

Hematology Department, Emergency University Hospital Bucharest, Romania.

We present the case of a patient with a double transformation during the evolution of chronic hematopoietic malignancy - JAK2 positive chronic myeloproliferative neoplasm; the first transformation had occurred previous to the presentation in our Department, but the second transformation was observed in evolution and it was into a rapidly evolving disease, followed by survival of less than one month. We underline the very poor prognosis -- overall survival of 2.5 years from initial presentation -- a much reduced survival for a chronic myeloproliferative neoplasm, probably due also to multiple associated pathology. Also, the other interesting element of the case is related to the dysfunctional platelets -- hemorrhagic complication at increased platelet count, respectively thrombosis at platelet count under 20000/mmc.
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March 2012

Perinatal outcome for pregnancies complicated with thrombocytopenia.

J Matern Fetal Neonatal Med 2012 Sep 14;25(9):1622-6. Epub 2012 Feb 14.

Hematology Department, Emergency University Hospital Bucharest, Elias University Emergency Hospital, Bucharest, Romania.

Introduction: Thrombocytopenia affects about 10% of all pregnancies. Preeclampsia/HELLP syndrome induced thrombocytopenia may associate perinatal morbidity, preterm delivery, or low-birth-weight newborns.

Objective: To assess perinatal outcome and complications of pregnancy in women presenting with thrombocytopenia.

Methods: We retrospectively analyzed 936 consecutive pregnant women admitted during a 6-month period.

Results: Incidence of thrombocytopenia in pregnancy was 11.11% (104/936). Thrombocytopenia represented a risk factor for premature delivery - highest risk for severe thrombocytopenia (RR=8.69, p<0.01). Thrombocytopenic preeclampsia or HELLP syndrome associated the highest rates of prematurity (RR=7.97, p=0.00, respectively 12.32). Thrombocytopenia also represented a risk factor for low-birth-weight newborns, especially severe thrombocytopenia - 2047.50 ± 938.98 g (p=0.02) versus 3224.86 ± 496.00 g in controls. Again, thrombocytopenic preeclampsia was significantly associated with low-birth-weight newborns (RR=11.94, p=0.00), with medium weight of 2462.05 ± 794.54 g versus 2932.37 ± 708.91 g in thrombocytopenic pregnancies, respectively 3224.86 ± 496.00 g (p=0.00) in normal pregnancies.

Conclusions: Thrombocytopenia in pregnancy was associated with perinatal morbidity, with the strongest association for preeclampsia and HELLP syndrome - for both prematurity and low-birth-weight: the lower the platelet count, the higher the risks for the fetus/newborn. Therefore, we strongly recommend close surveillance of thrombocytopenic mothers and their babies, in order to establish the etiology and the best moment for intervention.
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http://dx.doi.org/10.3109/14767058.2011.648245DOI Listing
September 2012

Platelet dysfunction in acute leukemias and myelodysplastic syndromes.

Rom J Intern Med 2011 ;49(1):93-6

The hemorrhagic and thrombotic diathesis represents a frequent complication in myelodysplastic syndromes (MDS) and in acute leukemias. They are correlated with the number of the platelets, but also with their qualitative disorders, such as membrane glycoprotein changes. The latter are revealed by many platelet studies including flow-cytometry and comprise modified activation, secretion and aggregation patterns.
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December 2011

Reactivation of HBV infection in low grade lymphoma patient.

Rom J Intern Med 2011 ;49(1):67-73

"Prof. Dr. Matei Balş" National Institute of Infectious Diseases, Bucharest.

Reactivation of hepatitis B virus is a complication of chronic or HBV infection in patients with malignancies, especially hematological disorders, under cytotoxic or immunosuppressive therapy. The immunosuppression favors HBV replication with the massive infection of hepatocytes. Once immunity is restored when chemotherapy therapy is discontinued, a rapid, immune-mediated destruction of the infected hepatocytes ensues, clinically manifested as hepatitis, liver failure or even death. We report a case of HBV reactivation in a patient with B cells non-Hodgkin lymphoma, with HBsAg negative and protective titre of anti-HBs, after 5 months of combined chemotherapy. Currently, there are no data to support routine pre-emptive anti-HBV therapy in patients with negative HBsAg and undetectable viremia before the initiation of chemotherapy. The case presented in this paper is included in the group of patients that is studied in LIMFOVIR Grant (convention no 41012/2007). This research grant is funded by the National Center of Programs Management, program 4 - Partnerships in Priority Fields. The grant is coordinated by the National Institute of Infectious Diseases Prof. Dr. Matei Bals, Bucharest. The grant team include also the Emergency University Hospital Bucharest, Hematology Department, the "Carol Davila" University of Medicine and Pharmacy, Bucharest, the "Victor Babeş" National Institute of Research and Development, the Institute of Electrotechnical Research, Bucharest and the Polytechnic University, Bucharest. The manager of the grant is Associated Professor dr. Victoria Aramă.
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December 2011

[Pathogenesis of thrombotic and hemorrhagic complications in myeloproliferative and myelodysplastic syndromes].

Rev Med Chir Soc Med Nat Iasi 2011 Jan-Mar;115(1):14-9

Facultatea de Medicină, Clinica de Hematologie SUUB, Universitatea de Medicini si Farmacie "C. Davila" Bucureşti.

Chronic myeloproliferative disorders (CMD) and Myelodisplastic Syndromes (MDS) represents a group of clonal pluripotent stem-cell pathologies. During their natural history, the clinical picture reveals both thrombosis and hemorrhage. The thrombosis could affect the microvessels, and also the large vessels, including even less usual territories (suprahepatic veins, porta vein, pulmonary vein). There are many factors contributing to thrombosis in myeloproliferative chronic disorders--the associated comorbidities, the numeric alterations of blood elements and also the disorders of the platelet's function. Thus, there were described quantitative and qualitative anomalies of platelet's receptors: GP Ib, GP IIb/IIIa, GP IV, GP VI, thrombopoietin receptor of the platelet cMPL, the increase of platelet activation; the increase of P selectin and thrombospondin and the increase on GP IIb/IIIa expression--they were all correlated with thrombosis. An important role has been attributed to JAK2 mutation, which affects the platelet receptor for thrombopoietin cMPL. Regarding the hemorrhage in chronic myeloproliferative syndrome, it is favored by many disorders in platelet's function, such as: the decrease of von Willebrand factor's receptor of the platelet, which leads to acquired Bernard Soulier syndrome; quantitative and qualitative disorders of dense granules of the platelet, decrease of the secretion and platelet aggregation after epinephrine, ADP and collagen stimulation. It was also described the acquired von Willebrand syndrome, most frequently type 2.
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July 2011

Chronic myeloid leukemia therapy in the era of tyrosine kinase inhibitors--the first molecular targeted treatment.

J Med Life 2010 Apr-Jun;3(2):162-6

"Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania.

Chronic Myeloid Leukemia is the first malignant disorder with a specific genetic abnormality in the background. Known as a disease with an inexorable progression to acute leukemia for many years, its natural history has been dramatically improved by the use of tyrosine kinase inhibitors (TKI). They represent the first molecular targeted therapy addressed to a neoplastic disorder. From these new classes of drugs, Imatinib was the first drug ever used, and it remains the standard therapy for patients in chronic phase with CML, having a global survival of 86%, for 7 years. The 2nd generation of TKI (Dasatinib, Nilotinib) is indicated for the patients who are refractory or intolerant to Imatinib. The other TKI have good promises to be efficient on the mutations of BCR-ABL transcript, especially to non-responsive T315I mutation.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3019054PMC
December 2010

The impact of hepatitis viruses on chronic lymphoproliferative disorders--preliminary results.

J Med Life 2010 Jul-Sep;3(3):320-9

Department of Hematology, Emergency Universitary Hospital, 169 Splaiul Independentei Street, Bucharest 050098, Romania.

Unlabelled: The aim of this study is to analyze a group of patients with chronic lymphoproliferative disorders associated with B, C, D hepatitis viral infection. This group of chronic lymphoproliferative disordered patients with associated hepatitis viral infection has been diagnosed and monitored in the Hematology Department of the University Emergency Hospital of Bucharest, between December 2007 and January 2009. Our study is meant to observe the influence of the viral infection on clinical and biological evolution of the enrolled patients. The diagnosis of the chronic lymphoproliferative disorder was based on the bone marrow/ lymph node biopsy and flow-cytometry analysis. The positive diagnosis for hepatitis viral infection was established by ELISA serological tests and viremia was performed by TaqMan method at INBI "Matei Bals" Bucharest. The analyzed group is made up of 41 patients, 25/41 (60.97%) females and 16/41 (39.02%) males, with ages: 20-50 years old--6/41 (14.63%), 51-70 years old--23/41 (56.09%) and over 71 years old--12/41 (29.26%) patients. The histological types of CLD: B-cell non-Hodgkin's lymphoma--in 28/41 (68.29%) patients, T-cell non-Hodgkin's lymphoma--2/41 (4.87%) patients, Hodgkin's lymphoma--2/41 (4.87%), chronic lymphocytic leukemia--7/41 (17.07%), Waldenström disease--2/41 (4.87%) patients. Regarding the type of CLD, 19/41 (46.34%) of the patients have an aggressive type of CLD and 22/41 (53.65%) a non-aggressive type of CLD. The hepatitis viral infection distribution in our patients: 14/41 (34.14%) have HBV infection, 24/41 (58.53%) have HCV infection, double/triple association of viral infection was found in 3/41 (7.31%) patients. Within HBV infection subgroup 9/14 (64.28%) patients have an aggressive type of CLD and 5/14 (35,71%) patients have a non-aggressive type, whereas within the group with HCV infection we found a different distribution: 9/24 (37,5%) patients with aggressive type and 15/24 (62.5%) with non-aggressive type of CLD. The clinical parameters monitored were: B signs were present in 19/41 (43.34%) patients, the superficial or profound adenopathies--were found in 29/41 (70,73%) patients, hepatomegaly--in 38/41 (92,68%) patients, splenomegaly--in 21/41 (51.21%) patients, extra-nodal involvements in 10/41 (24,39%) patients and most frequent in the non-aggressive type of CLD--6/10 (60%) patients. The hematological and biochemical parameters were: the presence of anemia and thrombocytopenia--found in a small number of patients; lymphocytosis--positive in 33/41 (80.48%) patients, most with HCV infection and non-aggressive type of disease, the presence of autoimmune hemolytic anemia--in 4/41 (9.75%) patients, cryoglobulins--8/41 (19.51%) patients, all with HCV infection; also the liver function was monitored. Antiviral therapy was administered to 12/41 (29.26%) patients--Lamivudine to 8/41 (19.51%) patients and Ribavirine/Interferon to 4/41 (9.75%) patients. Chemotherapy was given in 32/41 (78%) patients. Monoclonal antibodies anti CD20 (Rituximab) therapy was associated in 6/41 (14.63%) patients.

Conclusions: A high incidence in female sex of over 50 years old was noticed. A strong association between B-cell chronic lymphoproliferative disorders and hepatitis viral infection B, C, D was revealed, the most frequent being the C hepatitis virus, associated with the non-aggressive type of CLD, extra-nodal involvement, splenomegaly, lymphocytosis, cryoglobulins, cytolysis and colestasis. The clinical and biological disease history will be monitored during chemotherapy and antiviral treatment.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3019001PMC
December 2010

Splenectomy--a therapeutic option in splenic marginal zone cell lymphoma.

Rom J Intern Med 2009 ;47(2):191-9

Department of Hematology, Emergency Universitary Hospital Bucharest, Carol Davila University of Medicine and Pharmacy, Bucharest-UMFCD, Romania.

We present the case of a 65 years old male, admitted in the Hematology Department of the Universitary Emergency Hospital Bucharest, complaining of physical asthenia and weight loss; periodical medical examination has revealed splenomegaly and leucocytosis with lymphocytosis, persistent for the past 3 years. The clinical and paraclinical exam demonstrated splenomegaly (21 cm in diameter on computer tomography scan), hepatomegaly and generalized lymphadenopathies. The laboratory tests confirmed leucocytosis with lymphocytosis--a clonal population of B lymphocytes CD20+ CD19+ CD23+/- CD79b+(low), CD43+ FMC7+ CD5+ CD38+ ZAP70+ cyclin D1-. Lymph node and bone marrow biopsy together with flowcytometry established the diagnosis of Malignant non-Hodgkin Lymphoma--Atypical Splenic Marginal Zone B-cell lymphoma (aberrant expression of CD5) stage IVB, with leukemic picture, complicated with autoimmune hemolytic anemia with highly positive Coombs' tests. We performed therapeutic splenectomy, which was difficult because of the dimensions of the organ. The short term evolution was complicated by acute complete thrombosis of the splenic vein, but the long term evolution (1 year follow-up) was favorable--remission of anemia, significant improvement of performance status, decrease of leucocytosis and reduction of the tumoral mass.
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March 2010

An update on the platelet dysfunction in chronic myeloproliferative syndromes.

Rom J Intern Med 2008 ;46(1):9-15

Department of Hematology, Emergency Universitary Hospital, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.

The thrombotic and hemorrhagic diathesis represents a frequent complication in myeloproliferative disorders (CMPD). They are correlated with the number of platelets, but also with their qualitative disorders, such as membrane glycoprotein changes. The latter are revealed by many platelet essays including flow-cytometry and include modified activation, secretion and aggregation patterns. The thrombopoietin platelet receptor (cMPL), affected by the JAK2 V617 mutation encountered in CMPD, may be associated with a prothrombotic status. Its implication reveals the importance of the molecular genetics profile in defining molecular diagnostic hallmarks and makes it a candidate in the early diagnosis of myeloproliferative disorder and a predictor of thrombotic complications in this group of diseases.
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February 2009

Myeloma cells with asurophilic granules--an unusual morphological variant--case presentation.

J Med Life 2008 Jan-Mar;1(1):74-86

University of Medicine and Pharmacy Carol Davila, Clinic of Hematology Universitary Emergency Hospital, Bucharest.

We present the case of an 80-year-old man who was admitted for anemia, back pain and progressive weakness. After a workup of clinical and laboratory data, the final diagnosis was multiple myeloma. The bone marrow aspirate revealed 53% myeloma cells with peculiar and rare morphological features: numerous large asurophilic--bright red granules--mucopolizaccharides and immunoglobulins secreted and accumulated in the endoplasmic reticulum, typically known as Russel bodies.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3018960PMC
March 2010