Ana-maria Vlădăreanu - Academia.edu (original) (raw)
Papers by Ana-maria Vlădăreanu
Revista medico-chirurgicala a Societatii de Medici si Naturalisti din Iasi, 2011
Chronic myeloproliferative disorders (CMD) and Myelodisplastic Syndromes (MDS) represents a group... more 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 t...
Introduction Myelodysplastic syndromes (MDS) are a complex group of myeloid malignancies characte... more Introduction Myelodysplastic syndromes (MDS) are a complex group of myeloid malignancies characterized by peripheral blood cytopenia and dysplasia in bone marrow(1). MDS can appear de novo or can be secondary to environmental and occupational factors or to myelotoxic treatment. The majority of MDS patients cannot be cured, except for transplant-eligible patients(2). Therefore, most of them develop complications of the disease and treatment, such as infections and bleeding, or from transformation to acute myelogenous leukemia(1). Case presentation We present the case of a 79-year-old female who presented in our clinic with persistent pancytopenia for about 6 months. Her medical history is positive for rectal adenocarcinoma (ADK) diagnosed 16 months before, with complete remission after surgical treatment, chemotherapy with capecitabine and radiotherapy. Also, she has a positive family history of adenocarcinoma: her father with prostate ADK, and a sister with colonic ADK. She has a hi...
The primary central nervous system lymphoma (PCNSL) is a rare form of extranodal lymphoma that ca... more The primary central nervous system lymphoma (PCNSL) is a rare form of extranodal lymphoma that can affect the brain, the leptomeninges, the eye or the spinal cord, without any evidence of a systemic disease, having immunodeficiency as the main risk factor. The clinical presentation varies depending on the affected area. The diagnosis starts with a clinical suspicion, and must be supplemented by laboratory tests (blood and cerebrospinal fluid analysis) and imaging examinations. Even though the therapeutic protocols are limited, using the new treatments significantly increased the overall survival during time, but tumor relapse is still frequent and generally with poor prognosis.
Oncolog-Hematolog.ro, 2021
Oncolog-Hematolog.ro, 2021
Journal of Clinical Medicine, 2021
Anabolic androgenic steroids (AAS), simply called “androgens”, represent the most widespread drug... more 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 ...
Oncolog-Hematolog.ro, 2021
Imatinib mesilate (IM) is the first line therapy for chronic myeloid leukemia (CML) patients in c... more Imatinib mesilate (IM) is the first line therapy for chronic myeloid leukemia (CML) patients in chronic phase. Although it offers a complete cytogenetic response (CCyR) in a majority of patients, there still are some rare cases in which a sudden blast crisis (SBC) evolves. The mechanism of this unexpected event is not yet completely understood. We present the case of a female patient who developed a SBC while being under IM therapy. We do not know for sure which is the role of IM in this event, but current available data suggest that this drug may have a permissive effect on the evolution of some aggressive subclones in the context of restored normal cell population.
Myeloid disorders constitute a subgroup of hematological malignancies of myeloid lineage. In the ... more Myeloid disorders constitute a subgroup of hematological malignancies of myeloid lineage. In the revised 2008 WHO classification system, the nomenclature for myeloproliferative entities has been changed from "chronic myeloproliferative diseases" to "myeloproliferative neoplasms", the definition criteria has changed, and and the MDS/MPN has emerged as a well defined entity the subgroup formerly known as "myelodysplastic/myeloproliferative diseases" has changed to "myelodysplastic/myeloproliferative neoplasms". The World Health Organization classification of myeloid neoplasms relies on the association of clinical, morphologic, immunophenotypic and genetic diagnostic features. The current review highlights these changes and also provides diagnostic algorithms that are tailored to routine clinical practice.
We present the case of a 46-year-old male patient who came to our emergency department in Decembe... more We present the case of a 46-year-old male patient who came to our emergency department in December 2019 for pain in the left abdominal quadrant. The patient had no fever, night sweats or a history of weight loss. The laboratory tests revealed important leucocytosis and the abdominal ultrasound highlighted a massive splenomegaly. He was hospitalized for further investigations. We performed all the necessary laboratory tests to establish the diagnosis of the patient. Even though the osteomedullar biopsy and the flow cytometry suggested the diagnosis of acute B-cell lymphoblastic leukemia, the fluorescence in situ hybridization exam – the translocation t(9;22) was present in 100% of the analyzed cells – and the detection of BCR-ABL1 b2a2 transcript established the diagnosis of chronic myeloid leukemia, B-cell lymphoblastic crisis. We decided to start the treatment with the GRAAPH 2005 protocol associated with imatinib, and the patient was a candidate for all...
The thrombotic and hemorrhagic diathesis represents a frequent complication in myeloproliferative... more 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.
Romanian Medical Journal, Jun 30, 2019
In recent years understanding and modulating the tumor microenvironment (MT) has been the focus o... more In recent years understanding and modulating the tumor microenvironment (MT) has been the focus of a scientifically and clinically intense study. The role of T regulatory cells (Tregs) were investigated in terms of the suppression of tumor-specific immune responses and the establishment of an immunosuppressive tumor microenvironment (1). Regulatory T cells have a fundamental function in maintaining immune homeostasis in healthy individuals, and in cancer and in particular in haematological malignancies they seem to play a rather controversial role. Furthermore an increased frequency of Treg cells has been associated with tumor progression and has been correlated with an increased risk of death and reduced survival (2). The role of T cells in the pathogenesis of chronic lymphocytic leukemia has recently gained special attention due to the constant interaction between neoplastic B cells with the micromedium substrate and T cells. There is often a relatively large number of regulatory T cells in lymphoid tissues of CLL patients, that could affect the normal immune function (3).
Oncology Reports, 2010
The Philadelphia negative chronic myeloproliferative neoplasms are hematological disorders with s... more The Philadelphia negative chronic myeloproliferative neoplasms are hematological disorders with several diagnostic challenges. Due to recent molecular findings, the WHO classification of Tumors of Hematopoietic and Lymphoid Tissue 2008 reorganized the field of chronic myeloproliferative diseases. Thus, specific molecular markers provide important information for current diagnostic strategies. This review highlights the important diagnostic tools in classical and atypical myeloproliferative neoplasms mainly the JAK2V617F mutation, the Mpl receptor, Polycythemia rubra vera 1 (PRV1), platelet-derived growthfactor receptor • (PDGFRA), platelet-derived growth-factor receptor ß (PDGFRB), fibroblast growth-factor receptor 1 (FGFR1) and c-kit tyrosine kinase. A description of the origin, clinical correlations and role in diagnosis and therapy is provided for each of these molecular markers. Contents 1. Chronic myeloproliferative disorders 2. The role of molecular markers in myeloproliferative diseases 3. Conclusions
Address for correspondence: Ana-Maria Vladareanu, MD, PhD, Professor of Hematology, Hematology De... more Address for correspondence: Ana-Maria Vladareanu, MD, PhD, Professor of Hematology, Hematology Department, Emergency University Hospital, 169 Splaiul Independentei, Bucharest, Zip Code 050098, Romania email address: anamariavladareanu@yahoo.com ABSTRACT Hypereosinophilic syndromes are a heterogeneous group of disorders with low incidence, characterized by eosinophil blood count higher than 1,5x109/L persistent for at least 6 months in the absence of a reactive cause and with signs and symptoms of organ involvement due to the eosinophilia itself or to the release of eosinophilic mediators. Recent advances in molecular biology allowed a better understanding which led to a new classification of the hypereosinophilic syndromes corresponding to molecular abnormalities, offering the possibility of new therapeutic approaches. The utility of imatinib therapy in some of these new identified clinical and pathological entities dramatically improved the prognosis of these patients, justfying th...
Blood Coagulation & Fibrinolysis, 2015
Essential thrombocytemia - a classic myeloproliferative neoplasm characterized by persistent thro... more 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.
BMC Infectious Diseases, 2014
Romanian Medical Journal
For hematologic disorders, splenectomy has a wide range of applications: diagnosis, palliative or... more For hematologic disorders, splenectomy has a wide range of applications: diagnosis, palliative or curative. The most frequent indication is for red cell disorders: hereditary spherocytosis, autoimmune hemolytic anemia or thalassemia. For the platelet disorders, the greatest benefit is achieved in idiopathic thrombocytopenic purpura. In case of limfoproliferative disorders (leukemia, lymphoma), splenectomy plays a role in diagnosis, palliative care (lowering of tumor burden) and in some cases as a cure. In patients with hematologic disorders, splenectomy is associated with an elevated risk of infections that can be avoided with proper antibiotic prophylaxis and vaccination. Due to the expanding list of applications for splenectomy in hematologic disorder, it is necessary to establish a work protocol that covers all aspects and particularities of these disorders.
Romanian Journal of Medical Practice
Background. Patients with acute leukemia are at high risk to develop invasive fungal infections, ... more Background. Patients with acute leukemia are at high risk to develop invasive fungal infections, and Aspergillus spp is the most common pathogen. Aim. The two cases that are presented highlight the importance of adjusting the algorithm for diagnosis and treatment of invasive fungal infections in acute leukemia patients according to the particularities of each case in order to obtain an optimal response to the antifungal therapy. Methods and results. We present two cases of acute leukemia in young patients, who develop pulmonary invasive aspergillosis during severe neutropenia following chemotherapy. The diagnosis is clinical, mycrobiological, and esspecially imagistic, the CT scan revealing images typical for pulmonary invasive aspergillosis and allowing early antifungal therapy. Conclusions. The two cases illustrate the favourable outcome of patients with acute leukemia and pulmonary invasive aspergillosis when treated early with Voriconazole and the importance of dose adjusting ac...
Revista medico-chirurgicala a Societatii de Medici si Naturalisti din Iasi, 2011
Chronic myeloproliferative disorders (CMD) and Myelodisplastic Syndromes (MDS) represents a group... more 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 t...
Introduction Myelodysplastic syndromes (MDS) are a complex group of myeloid malignancies characte... more Introduction Myelodysplastic syndromes (MDS) are a complex group of myeloid malignancies characterized by peripheral blood cytopenia and dysplasia in bone marrow(1). MDS can appear de novo or can be secondary to environmental and occupational factors or to myelotoxic treatment. The majority of MDS patients cannot be cured, except for transplant-eligible patients(2). Therefore, most of them develop complications of the disease and treatment, such as infections and bleeding, or from transformation to acute myelogenous leukemia(1). Case presentation We present the case of a 79-year-old female who presented in our clinic with persistent pancytopenia for about 6 months. Her medical history is positive for rectal adenocarcinoma (ADK) diagnosed 16 months before, with complete remission after surgical treatment, chemotherapy with capecitabine and radiotherapy. Also, she has a positive family history of adenocarcinoma: her father with prostate ADK, and a sister with colonic ADK. She has a hi...
The primary central nervous system lymphoma (PCNSL) is a rare form of extranodal lymphoma that ca... more The primary central nervous system lymphoma (PCNSL) is a rare form of extranodal lymphoma that can affect the brain, the leptomeninges, the eye or the spinal cord, without any evidence of a systemic disease, having immunodeficiency as the main risk factor. The clinical presentation varies depending on the affected area. The diagnosis starts with a clinical suspicion, and must be supplemented by laboratory tests (blood and cerebrospinal fluid analysis) and imaging examinations. Even though the therapeutic protocols are limited, using the new treatments significantly increased the overall survival during time, but tumor relapse is still frequent and generally with poor prognosis.
Oncolog-Hematolog.ro, 2021
Oncolog-Hematolog.ro, 2021
Journal of Clinical Medicine, 2021
Anabolic androgenic steroids (AAS), simply called “androgens”, represent the most widespread drug... more 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 ...
Oncolog-Hematolog.ro, 2021
Imatinib mesilate (IM) is the first line therapy for chronic myeloid leukemia (CML) patients in c... more Imatinib mesilate (IM) is the first line therapy for chronic myeloid leukemia (CML) patients in chronic phase. Although it offers a complete cytogenetic response (CCyR) in a majority of patients, there still are some rare cases in which a sudden blast crisis (SBC) evolves. The mechanism of this unexpected event is not yet completely understood. We present the case of a female patient who developed a SBC while being under IM therapy. We do not know for sure which is the role of IM in this event, but current available data suggest that this drug may have a permissive effect on the evolution of some aggressive subclones in the context of restored normal cell population.
Myeloid disorders constitute a subgroup of hematological malignancies of myeloid lineage. In the ... more Myeloid disorders constitute a subgroup of hematological malignancies of myeloid lineage. In the revised 2008 WHO classification system, the nomenclature for myeloproliferative entities has been changed from "chronic myeloproliferative diseases" to "myeloproliferative neoplasms", the definition criteria has changed, and and the MDS/MPN has emerged as a well defined entity the subgroup formerly known as "myelodysplastic/myeloproliferative diseases" has changed to "myelodysplastic/myeloproliferative neoplasms". The World Health Organization classification of myeloid neoplasms relies on the association of clinical, morphologic, immunophenotypic and genetic diagnostic features. The current review highlights these changes and also provides diagnostic algorithms that are tailored to routine clinical practice.
We present the case of a 46-year-old male patient who came to our emergency department in Decembe... more We present the case of a 46-year-old male patient who came to our emergency department in December 2019 for pain in the left abdominal quadrant. The patient had no fever, night sweats or a history of weight loss. The laboratory tests revealed important leucocytosis and the abdominal ultrasound highlighted a massive splenomegaly. He was hospitalized for further investigations. We performed all the necessary laboratory tests to establish the diagnosis of the patient. Even though the osteomedullar biopsy and the flow cytometry suggested the diagnosis of acute B-cell lymphoblastic leukemia, the fluorescence in situ hybridization exam – the translocation t(9;22) was present in 100% of the analyzed cells – and the detection of BCR-ABL1 b2a2 transcript established the diagnosis of chronic myeloid leukemia, B-cell lymphoblastic crisis. We decided to start the treatment with the GRAAPH 2005 protocol associated with imatinib, and the patient was a candidate for all...
The thrombotic and hemorrhagic diathesis represents a frequent complication in myeloproliferative... more 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.
Romanian Medical Journal, Jun 30, 2019
In recent years understanding and modulating the tumor microenvironment (MT) has been the focus o... more In recent years understanding and modulating the tumor microenvironment (MT) has been the focus of a scientifically and clinically intense study. The role of T regulatory cells (Tregs) were investigated in terms of the suppression of tumor-specific immune responses and the establishment of an immunosuppressive tumor microenvironment (1). Regulatory T cells have a fundamental function in maintaining immune homeostasis in healthy individuals, and in cancer and in particular in haematological malignancies they seem to play a rather controversial role. Furthermore an increased frequency of Treg cells has been associated with tumor progression and has been correlated with an increased risk of death and reduced survival (2). The role of T cells in the pathogenesis of chronic lymphocytic leukemia has recently gained special attention due to the constant interaction between neoplastic B cells with the micromedium substrate and T cells. There is often a relatively large number of regulatory T cells in lymphoid tissues of CLL patients, that could affect the normal immune function (3).
Oncology Reports, 2010
The Philadelphia negative chronic myeloproliferative neoplasms are hematological disorders with s... more The Philadelphia negative chronic myeloproliferative neoplasms are hematological disorders with several diagnostic challenges. Due to recent molecular findings, the WHO classification of Tumors of Hematopoietic and Lymphoid Tissue 2008 reorganized the field of chronic myeloproliferative diseases. Thus, specific molecular markers provide important information for current diagnostic strategies. This review highlights the important diagnostic tools in classical and atypical myeloproliferative neoplasms mainly the JAK2V617F mutation, the Mpl receptor, Polycythemia rubra vera 1 (PRV1), platelet-derived growthfactor receptor • (PDGFRA), platelet-derived growth-factor receptor ß (PDGFRB), fibroblast growth-factor receptor 1 (FGFR1) and c-kit tyrosine kinase. A description of the origin, clinical correlations and role in diagnosis and therapy is provided for each of these molecular markers. Contents 1. Chronic myeloproliferative disorders 2. The role of molecular markers in myeloproliferative diseases 3. Conclusions
Address for correspondence: Ana-Maria Vladareanu, MD, PhD, Professor of Hematology, Hematology De... more Address for correspondence: Ana-Maria Vladareanu, MD, PhD, Professor of Hematology, Hematology Department, Emergency University Hospital, 169 Splaiul Independentei, Bucharest, Zip Code 050098, Romania email address: anamariavladareanu@yahoo.com ABSTRACT Hypereosinophilic syndromes are a heterogeneous group of disorders with low incidence, characterized by eosinophil blood count higher than 1,5x109/L persistent for at least 6 months in the absence of a reactive cause and with signs and symptoms of organ involvement due to the eosinophilia itself or to the release of eosinophilic mediators. Recent advances in molecular biology allowed a better understanding which led to a new classification of the hypereosinophilic syndromes corresponding to molecular abnormalities, offering the possibility of new therapeutic approaches. The utility of imatinib therapy in some of these new identified clinical and pathological entities dramatically improved the prognosis of these patients, justfying th...
Blood Coagulation & Fibrinolysis, 2015
Essential thrombocytemia - a classic myeloproliferative neoplasm characterized by persistent thro... more 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.
BMC Infectious Diseases, 2014
Romanian Medical Journal
For hematologic disorders, splenectomy has a wide range of applications: diagnosis, palliative or... more For hematologic disorders, splenectomy has a wide range of applications: diagnosis, palliative or curative. The most frequent indication is for red cell disorders: hereditary spherocytosis, autoimmune hemolytic anemia or thalassemia. For the platelet disorders, the greatest benefit is achieved in idiopathic thrombocytopenic purpura. In case of limfoproliferative disorders (leukemia, lymphoma), splenectomy plays a role in diagnosis, palliative care (lowering of tumor burden) and in some cases as a cure. In patients with hematologic disorders, splenectomy is associated with an elevated risk of infections that can be avoided with proper antibiotic prophylaxis and vaccination. Due to the expanding list of applications for splenectomy in hematologic disorder, it is necessary to establish a work protocol that covers all aspects and particularities of these disorders.
Romanian Journal of Medical Practice
Background. Patients with acute leukemia are at high risk to develop invasive fungal infections, ... more Background. Patients with acute leukemia are at high risk to develop invasive fungal infections, and Aspergillus spp is the most common pathogen. Aim. The two cases that are presented highlight the importance of adjusting the algorithm for diagnosis and treatment of invasive fungal infections in acute leukemia patients according to the particularities of each case in order to obtain an optimal response to the antifungal therapy. Methods and results. We present two cases of acute leukemia in young patients, who develop pulmonary invasive aspergillosis during severe neutropenia following chemotherapy. The diagnosis is clinical, mycrobiological, and esspecially imagistic, the CT scan revealing images typical for pulmonary invasive aspergillosis and allowing early antifungal therapy. Conclusions. The two cases illustrate the favourable outcome of patients with acute leukemia and pulmonary invasive aspergillosis when treated early with Voriconazole and the importance of dose adjusting ac...