scholarly journals How I treat essential thrombocythemia

Blood ◽  
2011 ◽  
Vol 117 (5) ◽  
pp. 1472-1482 ◽  
Author(s):  
Philip A. Beer ◽  
Wendy N. Erber ◽  
Peter J. Campbell ◽  
Anthony R. Green
Keyword(s):  
Polycythemia Vera ◽  
Essential Thrombocythemia ◽  
Molecular Mechanisms ◽  
Myeloproliferative Neoplasms ◽  
Primary Myelofibrosis ◽  
Current Approach ◽  
Diagnostic Process ◽  
Everyday Clinical Practice ◽  
Therapeutic Decisions ◽  
The Relationship

AbstractIn the past 5 years we have witnessed significant advances in both the diagnostic process and optimal therapy for patients with essential thrombocythemia (ET). Insights into the underlying molecular mechanisms have been accompanied by the development of new diagnostic tests and by an improved understanding of the relationship between ET and other related myeloproliferative neoplasms, such as polycythemia vera and primary myelofibrosis. In the first part of this review, we describe how recent molecular and histologic studies can be integrated into a streamlined diagnostic process that is applicable to everyday clinical practice. We also address areas of current diagnostic controversy, including heterogeneity within ET and the phenotypic overlap between ET, polycythemia vera, and primary myelofibrosis. In the second part, we provide an overview of our current approach to the treatment of ET, including risk stratification, choice of cytoreductive agent, and a consideration of special situations such as the pregnant or perioperative patient. Areas of controversy discussed include the identification of those at high risk of complications and therapeutic decisions in the younger patient.

Pathogenesis and management of essential thrombocythemia

Hematology ◽  
2009 ◽  
Vol 2009 (1) ◽  
pp. 621-628 ◽  
Author(s):  
Philip A. Beer ◽  
Anthony R. Green
Keyword(s):  
Polycythemia Vera ◽  
Essential Thrombocythemia ◽  
Diagnostic Tests ◽  
Molecular Mechanisms ◽  
Myeloproliferative Neoplasms ◽  
Primary Myelofibrosis ◽  
Recent Developments ◽  
Disease Entities ◽  
The Relationship

Abstract The last four years have seen an explosion in our understanding of the myeloproliferative neoplasms. Important and often unexpected insights into the molecular mechanisms responsible for these disorders have been accompanied by the development of new diagnostic tests and by an improved understanding of the relationship between the different disease entities. This review will focus on recent developments in the pathogenesis and management of essential thrombocythemia with a particular emphasis on its phenotypic overlap with polycythemia vera and primary myelofibrosis.

scholarly journals Splenomegaly impacts prognosis in essential thrombocythemia and polycythemia vera: A single center study

2019 ◽  
Vol 11 (4) ◽  
Author(s):  
Vincenzo Accurso ◽  
Marco Santoro ◽  
Simona Raso ◽  
Angelo Davide Contrino ◽  
Paolo Casimiro ◽  
...  
Keyword(s):  
Polycythemia Vera ◽  
Essential Thrombocythemia ◽  
Myeloproliferative Neoplasms ◽  
Clinical Manifestations ◽  
Primary Myelofibrosis ◽  
Thrombotic Risk ◽  
Single Center Study ◽  
The Impact ◽  
The Relationship

Splenomegaly is one of the major clinical manifestations of primary myelofibrosis and is common also in other chronic Philadelphia-negative myeloproliferative neoplasms, causing symptoms and signs and affecting quality of life of patients diagnosed with these diseases. We aimed to study the impact that such alteration has on thrombotic risk and on the survival of patients with essential thrombocythemia and patients with Polycythemia Vera (PV). We studied the relationship between splenomegaly (and its grade), thrombosis and survival in 238 patients with et and 165 patients with PV followed at our center between January 1997 and May 2019.

scholarly journals Thrombocytosis: Diagnostic Evaluation, Thrombotic Risk Stratification, and Risk-Based Management Strategies

Thrombosis ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-16 ◽  
Author(s):  
Jonathan S. Bleeker ◽  
William J. Hogan
Keyword(s):  
Polycythemia Vera ◽  
Essential Thrombocythemia ◽  
Myeloproliferative Neoplasms ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Diagnostic Evaluation ◽  
Diagnostic Process ◽  
Special Focus ◽  
Thrombotic Risk ◽  
Increased Risk

Thrombocytosis is a commonly encountered clinical scenario, with a large proportion of cases discovered incidentally. The differential diagnosis for thrombocytosis is broad and the diagnostic process can be challenging. Thrombocytosis can be spurious, attributed to a reactive process or due to clonal disorder. This distinction is important as it carries implications for evaluation, prognosis, and treatment. Clonal thrombocytosis associated with the myeloproliferative neoplasms, especially essential thrombocythemia and polycythemia vera, carries a unique prognostic profile, with a markedly increased risk of thrombosis. This risk is the driving factor behind treatment strategies in these disorders. Clinical trials utilizing targeted therapies in thrombocytosis are ongoing with new therapeutic targets waiting to be explored. This paper will outline the mechanisms underlying thrombocytosis, the diagnostic evaluation of thrombocytosis, complications of thrombocytosis with a special focus on thrombotic risk as well as treatment options for clonal processes leading to thrombocytosis, including essential thrombocythemia and polycythemia vera.

scholarly journals MPL W515 L/K mutations in myeloproliferative neoplasms

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Sohaila Eldeweny ◽  
Hosny Ibrahim ◽  
Ghada Elsayed ◽  
Mohamed Samra
Keyword(s):  
Bone Marrow ◽  
Polycythemia Vera ◽  
Ethnic Groups ◽  
Essential Thrombocythemia ◽  
Myeloproliferative Neoplasms ◽  
Primary Myelofibrosis ◽  
Myelogenous Leukemia ◽  
Egyptian Population ◽  
Ph Chromosome ◽  
Pathological Variant

Abstract Background Myeloproliferative neoplasms (MPNs) describe a group of diseases involving the bone marrow (BM). Classical MPNs are classified into chronic myelogenous leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). This classification is based on the presence of Philadelphia (Ph) chromosome (BCR/ABL1). CML is BCR/ABL1-positive while PV, ET, and PMF are negative. JAK2 p. Val617Phe pathological variant is the most associated mutation in BCR/ABL1-negative MPNs. The frequency of JAK2 p. Val617Phe is 90–95% in PV patients, 50–60% in ET, and 40–50% in patients with PMF. Studies on MPL gene led to the revelation of a gain of function pathological variants in JAK2 p. Val617Phe-negative myeloproliferative neoplasms (MPNs). MPL p. W515 L/K pathological variants are the most common across all mutations in MPL gene. The prevalence of these pathological variants over the Egyptian population is not clear enough. In the present study, we aimed to investigate the prevalence of MPL p. W515 L/K pathological variants in the Philadelphia (Ph)-negative MPNs over the Egyptian population. Results We have tested 60 patients with Ph-negative MPNs for MPL p. W515 L/K pathological variants. Median age was 51 (22–73) years. No MPL p. W515 L/K pathological variants were detected among our patients. JAK2 p. Val617Phe in PV and PMF patients showed significantly lower frequency than other studies. Splenomegaly was significantly higher in ET patients compared to other studies. Conclusion MPL p. W515 L/K pathological variants are rare across the Egyptian Ph-negative MPNs, and further studies on a large number are recommended. MPN patients in Egypt are younger compared to different ethnic groups.

High Mitochondrial Membrane Potential Identifies Patients with Myeloproliferative Neoplasms with a More Aggressive Natural History

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1992-1992
Author(s):  
Jeffrey R Gardner ◽  
Omar Abdel-Wahab ◽  
Mark Frattini ◽  
Joseph G Jurcic ◽  
Kristina Knapp ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Polycythemia Vera ◽  
Mitochondrial Membrane Potential ◽  
Essential Thrombocythemia ◽  
Blood Cells ◽  
Myeloid Leukemia ◽  
Mitochondrial Membrane ◽  
Myeloproliferative Neoplasms ◽  
Primary Myelofibrosis ◽  
Acute Myeloid

Abstract Abstract 1992 The myeloproliferative neoplasms (MPN) can have a variable natural history. Polycythemia vera and essential thrombocythemia, in particular, are conditions that can extend over decades, but some patients have clinical progression to myelofibrosis or acute myeloid leukemia. As first articulated by Warburg, cancers are metabolically distinguished from normal tissues by the use of glycolysis under aerobic conditions. To metabolically characterize the blood cells of patients with myeloproliferative neoplasms, we measured the mitochondrial membrane potential using the cyanine dye, JC-1. In examining cells derived from the blood and/or marrow of 159 patients with primary myelofibrosis, polycythemia vera and essential thrombocythemia, we found that the mitochondrial membrane potential (FL2/FL1=electrochemical potential/mitochondrial mass) was elevated compared to the blood cells of normal individuals. Thirty five percent of patients with polycythemia vera and essential thrombocythemia had normal MMP. In contrast, 97% of patients with primary myelofibrosis, post-polycythemia myelofibrosis, post-essential thrombocythemia myelofibrosis and acute myeloid leukemia following an MPN had evidence of cell populations with higher mitochondrial membrane potential. Cells with distinctly higher mitochondrial membrane potential could be indentified in platelets and polymorphonuclear leukocytes; however the MMP of lymphocytes was normal, indicating that the alteration in metabolic state likely occurred in a multipotential myeloid stem cell. Cell populations were confirmed by co-staining with anti-CD19, -CD45, -GlycophorinA and -β3-integrin antibodies. Sequential analysis of patient samples found that the acquisition of higher mitochondrial membrane potential was stable and persistent over 2 years or more of follow up and that elevated membrane potential predisposed patients to disease progression. The balance of patients (65%) with ET had evidence of increased MMP suggesting the possibility of disease in an early state of evolution to a more aggressive condition. The increased MMP did not correlate with the presence of mutation in JAK2. These results indicate that clinically advanced MPN can be characterized by changes in mitochondrial physiology that might be identified non-invasively by flow cytometric staining with JC-1. In addition, the early nature of these changes may help to identify therapeutic targets. Disclosures: No relevant conflicts of interest to declare.

scholarly journals AB0825 JAK2 (V617F) MUTATION AND ASSOCIATION TO IMMUNE MEDIATED DISEASES. STUDY OF 130 PATIENTS FROM A SINGLE UNIVERSITY HOSPITAL

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1436.2-1437
Author(s):  
C. Álvarez-Reguera ◽  
L. Sanchez-Bilbao ◽  
A. Batlle-López ◽  
S. Fernández López ◽  
M. Á. González-Gay ◽  
...  
Keyword(s):  
Deep Vein Thrombosis ◽  
Venous Thromboembolism ◽  
Polycythemia Vera ◽  
Essential Thrombocythemia ◽  
Myeloproliferative Neoplasms ◽  
Primary Myelofibrosis ◽  
Vein Thrombosis ◽  
Immune Mediated ◽  
V617f Mutation ◽  
Deep Vein

Background:Janus Kinases (JAK) are tirosin-kinases that can promote cytokine production in immune and hematopoietic cells. The JAK-2 (V617F) mutation is the most frequently detected mutation in myeloproliferative neoplasms (MPN) which include essential thrombocythemia (ET), polycythemia vera (PV), primary myelofibrosis (PMF) and undifferenciated MPN. JAK-2 (V617F) mutation displays a pro-inflammatory phenotype that may be associated to a higher risk of immune mediated diseases (IMID), thromboembolic complications or other cancers (1-3).Objectives:To evaluate the presence of a) IMID (rheumatic and non-rheumatic), b) cancer and, c) Deep vein thrombosis/ Venous thromboembolism (DVT/VTE) events in a cohort of patients with a positive JAK-2 (V617F) mutation.Methods:We studied all the patients diagnosed with a positive JAK-2 (V16F) mutation in a single University Hospital between January, 2004 and December, 2019.Results:The study included 130 patients (73 men/57 women; mean age, 70.1±14.5 years). They were diagnosed of ET (n=64, 49.2%), PV 46 (35.4%), undifferentiated MPN (n=12, 9.2%) and PMF (n=8, 6.1%). Of these patients, 54 (41.5 %) (44 non rheumatic and 10 rheumatic) were diagnosed with at least one IMID, 46 (35.4%) with other cancer different of MPN and 36 (27.7%) with DVT/VTE events. (Table 1/Figure 1).Conclusion:Due to its prevalence and potential complications, IMID should be taken into consideration when a patient is diagnosed with a positive JAK-2 (V617F) mutation.References:[1]Perner F, et al. Cells. 2019;8:854.[2]Xu Q, et al. Clin Rheumatol. 2020 Jul 16.[3]Hasselbalch HC, et al. 2020; 23;17(1):248.Table 1.Associated diseases in 130 patients with JAK2 (V617F) mutation. Data are n (%)Myeloproliferative neoplasms (MPN)130 (100) Essential thrombocythemia (ET)64 (49.2) Polycythemia vera (PV)46 (35.4) Undifferentiated MPN12 (9.2) Primary myelofibrosis (PMF)8 (6.5)Non-rheumatic IMID44 (33.8) Diabetes mellitus22 (50) Asthma10 (22.7) Psoriasis6 (13.6) Crohn disease2 (4.5) Autoimmune thyroiditis2 (4.5)Rheumatic IMID10 (7.7) Rheumatoid arthritis4 (40) Polymyalgia rheumatica3 (30) Sjögren disease1 (10) Antiphospholipid syndrome1 (10) Adult-onset Still’s disease1 (10)Malignancies different of MPN44 (33.8) Solid tumours // Hematologic malignancies // Skin cancer22 (50) // 13 (29.5) // 9 (20.4)Deep vein thrombosis/Venous thromboembolism (DVT/VTE) events35 (26.9)Figure 1.Associated diseases accordingly to the subtype of Myeloproliferative neoplasm. Data are n.ABBREVIATIONS: DVT/VTE: Deep vein thrombosis/ Venous thromboembolism. ET: Essential Thrombocythemia, IMID: Immune Mediated Diseases, PV: Polycythemia Vera; MPN: Myeloproliferative Neoplasms; PMF: Primary myelofibrosis; UMPN: Undifferenciated myeloproliferative neoplasms.Disclosure of Interests:Carmen Álvarez-Reguera: None declared, Lara Sanchez-Bilbao: None declared, Ana Batlle-López: None declared, Sara Fernández López: None declared, Miguel Á. González-Gay Speakers bureau: Abbvie, Pfizer, Roche, Sanofi and MSD., Grant/research support from: Abbvie, MSD, Janssen and Roche, Ricardo Blanco Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen, Lilly and MSD., Grant/research support from: Abbvie, MSD and Roche

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