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3.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(5): 1540-1547, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34627437

RESUMO

OBJECTIVE: To analyze the disease types, clinical manifestations, efficacy and outcome of JAK2 V617F and BCR-ABL double-mutant myeloproliferative neoplasms (MPN), and provide a reference for the diagnosis, treatment and prognosis of MPN. METHODS: The clinical characteristics, diagnosis, therapeutic efficacy and outcome of JAK2 V617F and BCR-ABL double-mutant MPN were analyzed comprehensitively by combining a clinical case diagnosed and treated in our hospital with literature cases from CNKI and PubMed databases. RESULTS: A total of 38 related literatures were retrieved from the two databases by searching "JAK2 V617F" and "BCR-ABL" as key words from 1990 to 2019, and 59 cases were involved. Among all the 60 cases, 41 were males (68.3%) with a median age of 61 (32-77) years old, while 19 were females (31.7%) with a median age of 58 (21-82) years old. The BCR-ABL fusion gene and JAK2 V617F mutation were found simultaneously in 21 cases (35%), 19 cases (31.7%) with JAK2 V617F mutation were found during the treatment of Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML). Ph+CML was detectable in 20 cases (33.3%) during the treatment of JAK2 V617F mutation positive MPN. Polycythemia vera (PV) was the most common MPN coexisting with CML (30%), followed by essential thrombocythemia (ET) (26.7%) and primary myelofibrosis (PMF) (21.7%). In addition, there were 13 cases (21.7%) not classified in the literature. Among the 60 cases, 35 CML patients were clearly staged, including 31 in the chronic phase, 3 in the accelerated phase, and 1 in the blast crisis phase. As for the subtypes of BCR-ABL fusion gene, there were 30 cases with clear classification, including 28 cases of p210, 1 case of p190 and 1 case of p230. CONCLUSION: As cases of BCR-ABL and JAK2 V617F double-mutant MPN are reported, simultaneous detection of JAK2 V617F mutation and BCR-ABL fusion gene in MPN patients is necessary to avoid misdiagnosis and missed diagnosis.


Assuntos
Transtornos Mieloproliferativos , Policitemia Vera , Trombocitemia Essencial , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Proteínas de Fusão bcr-abl/genética , Humanos , Janus Quinase 2/genética , Masculino , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/genética , Adulto Jovem
4.
Pan Afr Med J ; 39: 194, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34603575

RESUMO

Myeloproliferative neoplasms (MPNs) comprise polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). The relationship between JAK2 p.(V617F) mutation and MPNs was first described in 2005. The purpose of this study was to determine the prevalence of JAK2 p.(V617F) mutation in Tunisian patients assessed for MPNs and try to set a genotype-phenotype correlation. A retrospective study was conducted between January 2015 and April 2019. We collected the clinical data of all patients with MPNs suspicion or atypical splanchnic vein thrombosis (SVT). JAK2 p.(V617F) mutation was detected by allele specific real-time quantitative fluorescence PCR (AS-qPCR). We gathered 974 patients who underwent molecular analysis, 55.5% of them were male and 44.5% were female. The median age of all studied patients was 56 years. JAK2 p.(V617F) was found in 349 (35.8%) of total enrolled cases. It was reported in 44%, 37%, 29% and 25% of all patients diagnosed as having respectively ET, PV, PMF and atypical SVT. JAK2 p.(V617F) was negative in 62.2% of patients addressed for suspicion of PV. There was a significant positive correlation between the JAK2 p.(V617F) mutation status, age, gender, white blood cell counts and platelet counts. To our best knowledge, this is the first vast investigation of JAK2 p.(V617F) variant in Tunisia and North Africa with the lowest mutation rate in entire cohort and MPNs subgroups, underlying a specific presentation of this mutation. It is considered as an essential marker of MPNs' diagnosis and prognosis and is associated with differences in the phenotype of these disorders, helpful for the follow-up of these patients.


Assuntos
Janus Quinase 2/genética , Policitemia Vera/genética , Mielofibrose Primária/genética , Trombocitemia Essencial/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Criança , Pré-Escolar , Feminino , Estudos de Associação Genética , Variação Genética , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Mutação , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Tunísia , Adulto Jovem
5.
Arq. bras. cardiol ; 117(4 supl.1): 12-12, out., 2021.
Artigo em Português | Sec. Est. Saúde SP, CONASS, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1292855

RESUMO

INTRODUÇÃO: O termo MINOCA (Myocardial Infarction With Nonobstructive Coronary Arteries) é utilizado para os casos de infarto agudo do miocárdio em que as coronárias apresentam lesões menores que 50% na cineangiocoronariografia. Na literatura este tipo de infarto ocorre entre 5-6% dos pacientes e tem como causa uma variedade de condições clínicas. Reconhecê-las é de grande importância para estabelecer um tratamento específico da causa subjacente. DESCRIÇÃO DO CASO: Paciente de 50 anos, sexo feminino, sem comorbidades conhecidas, admitida em serviço externo por queixa de dor precordial típica, iniciada há 3 horas da admissão. O exame físico de entrada sem alterações e sinais vitais estáveis. O eletrocardiograma de entrada apresentava supradesnivelamento do segmento ST em parede anterior extensa, sendo optado por trombólise com critérios de reperfusão. Neste serviço foram registradas troponinas dosadas qualitativamente positivas durante evento agudo. A paciente foi encaminhada para estratificação invasiva em hospital terciário de forma tardia, sendo um mês após o evento. Na cineangiocoronariografia, foi observada lesão segmentar de até 20% no terço proximal da artéria descendente anterior e sem outras lesões. Diante do quadro típico de infarto agudo do miocárdio, com a cineangiocoronariografia demonstrando estenose ≤50%, com exclusão de outras causas clínicas, foi dado o diagnóstico de MINOCA. Durante investigação, observado plaquetose de 1.200.000/mm³, sendo avaliada pela equipe de Hematologia, recebendo diagnóstico de trombocitemia essencial (com mutação da JAK 2 positiva). Paciente evoluiu sem intercorrências, com seguimento e tratamento específico para doença hematológica diagnosticada. CONCLUSÕES: Relatamos um caso de MINOCA como primeira manifestação clínica de trombocitemia essencial. No caso clínico em questão, há diversas etiologias plausíveis para esta síndrome. O estado de hipercoagulabilidade decorrente da neoplasia hematológica de base, possível embolização distal e trombose transitória resolvida com a trombólise poderiam ser as causas. É fundamental que profissionais de saúde tenham maior compreensão da prevalência e tratamento das várias condições que resultam em MINOCA, a fim de obtermos melhores resultados clínicos.


Assuntos
Trombocitemia Essencial/diagnóstico , Infarto do Miocárdio
6.
Cancer Treat Res ; 181: 151-165, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34626360

RESUMO

The classical myeloproliferative neoplasms (MPN) are characterized by clonal expansion of one or more hematopoietic cell lineages and are driven by mutations that activate constitutive signaling via JAK2 pathway. The criteria for diagnosis have now been defined by the World Health Organization (WHO) and the term MPN as is currently used encompasses the entities of primary myelofibrosis, polycythemia vera, and essential thrombocytosis. There is imperfect correlation between the genotype and disease phenotype in MPN and the latter is determined by a variety of patient factors that are independent of the driver mutation. The disease course in MPN can span decades and accurate risk assessment is critical in the choice of therapy and treatment is largely geared toward prevention of complications and providing symptomatic relief. Although new agents have been approved in recent years, no therapy has been convincingly shown to alter disease progression and allogeneic hematopoietic stem cell transplantation (HCT) remains the only curative therapy known to date.


Assuntos
Transtornos Mieloproliferativos , Policitemia Vera , Mielofibrose Primária , Trombocitemia Essencial , Biologia , Humanos , Mutação , Transtornos Mieloproliferativos/genética , Transtornos Mieloproliferativos/terapia , Mielofibrose Primária/diagnóstico , Mielofibrose Primária/genética , Mielofibrose Primária/terapia
7.
Ann Biol Clin (Paris) ; 79(5): 415-425, 2021 Oct 01.
Artigo em Francês | MEDLINE | ID: mdl-34642137

RESUMO

During a blood test, the discovery of thrombocytosis is a frequent phenomenon with multiple origins. False thrombocytosis linked to analytical interferences is rare but must be eliminated before confirming the anomaly. The reaction origin, often very easily demonstrated by the context and/or the presence of a biological inflammatory syndrome, is the most frequent. More rarely, the diagnosis is oriented towards a clonal hematological pathology not limited to essential thrombocythemia. Currently, many biological tools, which have largely contributed to the recommendations of the latest WHO classification of chronic myeloid neoplasms, are available to classify these pathologies as precisely as possible, allowing optimal management.


Assuntos
Transtornos Mieloproliferativos , Trombocitemia Essencial , Trombocitose , Adulto , Humanos , Trombocitemia Essencial/diagnóstico , Trombocitose/diagnóstico
8.
Rev Assoc Med Bras (1992) ; 67(3): 385-389, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34468602

RESUMO

OBJECTIVE: The aim of this study was to compare the incidence of factors associated with an increased risk of thrombosis in patients with essential thrombocythemia. METHODS: A total of 200 patients followed-up in our unit with a diagnosis of essential thrombocythemia in 13 years were analyzed retrospectively. RESULTS: Of the study participants, 60.5% were females and 39.5% were males, with an overall mean (±SD) age of 54.93 (±14.21) years. In 119 patients, Janus Kinase 2 was positive with 56.3% of cases. When two patient categories were defined as those with or without history of thrombosis, no significant differences were found in terms of Janus Kinase 2 positivity, mean age, as well as white blood cells and platelet counts (p>0.05). Also, no significant differences in thrombotic event incidence were found between patient categories defined on the basis of cut-off values for white blood cells (cut-off values of 15×103/mm3 and 8.7×103/mm3) and platelets (cut-off values of 1500×103/mm3) (p>0.05). CONCLUSION: Although our results are generally in line with the published data, some divergence from previous results has been observed with respect to risk factors for thrombotic events. Absence of a correlation between leukocytosis and thrombosis may be related with the significant decline in white blood cells after treatment. Also, a significant reduction in platelet counts occurring in association with treatment is linked with a lowered incidence of thrombosis. Janus Kinase 2-positive patients had a similar thrombosis frequency with that reported in the literature.


Assuntos
Trombocitemia Essencial , Trombose , Adulto , Idoso , Plaquetas , Feminino , Humanos , Janus Quinase 2 , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Trombocitemia Essencial/complicações , Trombocitemia Essencial/epidemiologia , Trombose/epidemiologia , Trombose/etiologia
9.
BMJ Case Rep ; 14(9)2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34561237

RESUMO

Essential thrombocythaemia (ET) is a myeloproliferative neoplasm where there is a clonal proliferation of thrombocytes. Whilst most often diagnosed incidentally, it can uncommonly present with arterial thrombosis. This is a case presentation of a 36-year-old male who was diagnosed with ET following myocardial infarction caused by multiple thrombotic emboli. The patient was initially misdiagnosed with viral myopericarditis based on an atypical history of chest pain with a viral prodrome. Reattendance a month later with further chest pain, dynamically raised troponin and ECG changes raised suspicions of ACS. Analysis of blood markers from both admissions showed consistently elevated platelet counts. A CMR scan revealed focal ischaemic scars in multiple cardiac segments consistent with an acute coronary event or coronary embolisation. A subsequent coronary angiography demonstrated minimal coronary artery disease. JAK2 gene V617F mutation was detected, confirming ET. The patient was commenced on pegylated interferon-alpha and dual antiplatelet therapy, and discharged with follow-up.


Assuntos
Doença da Artéria Coronariana , Infarto do Miocárdio , Trombocitemia Essencial , Adulto , Dor no Peito/etiologia , Angiografia Coronária , Humanos , Masculino , Infarto do Miocárdio/diagnóstico , Trombocitemia Essencial/complicações , Trombocitemia Essencial/diagnóstico , Trombocitemia Essencial/tratamento farmacológico
10.
BMJ Case Rep ; 14(9)2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34544722

RESUMO

A 63-year-old diabetic woman presented to the outpatient clinic with a 1-week history of abdominal pain. On complete evaluation, she was diagnosed to have essential thrombocythemia. Abdominal imaging revealed portal vein thrombosis with a large splenic infarct. The patient was started on anticoagulant, antiplatelet and cytoreductive therapy. In view of persistent high platelet count, plasma apheresis was done, following which the patient's platelet counts were reduced. Essential thrombocythemia has a high rate of complications, resulting in significant morbidity and mortality. Few cases of this disease and its treatment have been described in the literature, especially pertaining to the Indian scenario. Further studies are needed to establish a multidisciplinary algorithm for its diagnosis and to elucidate the guidelines for the successful treatment of the condition.


Assuntos
Infarto do Baço , Trombocitemia Essencial , Trombose Venosa , Feminino , Humanos , Pessoa de Meia-Idade , Contagem de Plaquetas , Veia Porta/diagnóstico por imagem , Infarto do Baço/diagnóstico por imagem , Infarto do Baço/etiologia , Infarto do Baço/terapia , Veia Esplênica , Trombocitemia Essencial/complicações , Trombocitemia Essencial/terapia , Trombose Venosa/terapia
11.
Rinsho Ketsueki ; 62(8): 1050-1059, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34497191

RESUMO

Essential thrombocythemia (ET) and polycythemia vera (PV) are myeloproliferative neoplasms (MPN), wherein JAK2 V617F mutation exists as a common driver mutation, and the JAK-STAT pathway is constitutively activated. The treatment goal for ET and PV is the prevention of thrombosis and bleeding. The treatment strategy for ET is careful observation or antiplatelet therapy with or without cytoreductive therapy based on the thrombotic risk. The treatment strategy for all PV patients is phlebotomy with a target hematocrit of <45% in addition to antiplatelet therapy. Moreover, for patients at a high risk of thrombosis, additional cytoreductive therapy is considered beneficial. In this session, we discuss important points for ET diagnosis, thrombotic risk stratification, and the details of treatment strategy and current practice with evidence from clinical trials in ET. Furthermore, current topics in the treatment of ET and PV will be introduced with a focus on clinical data about interferon-α, which is reported to induce not only hematologic response but also molecular and histopathologic response in MPN.


Assuntos
Transtornos Mieloproliferativos , Policitemia Vera , Trombocitemia Essencial , Trombose , Hemorragia , Humanos , Janus Quinase 2/genética , Policitemia Vera/diagnóstico , Policitemia Vera/terapia , Trombocitemia Essencial/diagnóstico , Trombocitemia Essencial/genética , Trombocitemia Essencial/terapia , Trombose/etiologia , Trombose/prevenção & controle
12.
Curr Hematol Malig Rep ; 16(5): 473-482, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34478054

RESUMO

PURPOSE OF REVIEW: Essential thrombocythemia (ET) and polycythemia vera (PV) are the most common myeloproliferative neoplasms (MPNs). Treatment of ET and PV is based on the risk for subsequent thrombosis. High-risk patients, defined as older than 60, JAK2 V617F-positive patients, or patients with a history of prior thrombosis, merit cytoreduction to control blood counts, whereas a watchful waiting paradigm is utilized in low-risk patients. However, low-risk patients have a host of other specific management issues that arise during their disease course. This review will discuss the most common management issues specific to the care of low-risk patients, including anti-platelet therapy dosing, pregnancy, and indications for early cytoreduction. RECENT FINDINGS: Although low-dose aspirin is well established in PV, its indications and dosing regimens are less clear in ET. Recent evidence has supported twice daily low-dose aspirin in ET and observation alone in very low-risk ET patients. Pregnancy is not contraindicated in MPNs, and we recommend aspirin throughout pregnancy with consideration for prophylactic postpartum anticoagulation. High phlebotomy needs, symptom burden, and extreme thrombocytosis are common reasons for initiation of cytoreduction in low-risk patients, although we typically do not start cytoreduction for an isolated high platelet count alone. Recent data has also demonstrated a potential disease-modifying effect of interferons in MPNs, with some experts now advocating the early use of interferon in low-risk patients, although more mature data is needed before practice guidelines change. We evaluate the literature to inform clinical decision-making regarding these controversies, including most recent data that has challenged the "watchful waiting" paradigm. Our discussion provides guidance on common clinical scenarios seen in low-risk ET and PV patients, who face a myriad of complex management decisions in their care.


Assuntos
Policitemia Vera/terapia , Trombocitemia Essencial/terapia , Animais , Aspirina/uso terapêutico , Gerenciamento Clínico , Feminino , Humanos , Flebotomia , Inibidores da Agregação Plaquetária/uso terapêutico , Gravidez , Complicações Hematológicas na Gravidez/terapia
13.
Cells ; 10(9)2021 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-34571965

RESUMO

Myeloproliferative Neoplasms (MPN) are acquired clonal disorders of the hematopoietic stem cells and include Essential Thrombocythemia, Polycythemia Vera and Myelofibrosis. MPN are characterized by mutations in three driver genes (JAK2, CALR and MPL) and by a state of chronic inflammation. Notably, MPN patients experience increased risk of thrombosis, disease progression, second neoplasia and evolution to acute leukemia. Extracellular vesicles (EVs) are a heterogeneous population of microparticles with a role in cell-cell communication. The EV-mediated cross-talk occurs via the trafficking of bioactive molecules such as nucleic acids, proteins, metabolites and lipids. Growing interest is focused on EVs and their potential impact on the regulation of blood cancers. Overall, EVs have been suggested to orchestrate the complex interplay between tumor cells and the microenvironment with a pivotal role in "education" and "crafting" of the microenvironment by regulating angiogenesis, coagulation, immune escape and drug resistance of tumors. This review is focused on the role of EVs in MPN. Specifically, we will provide an overview of recent findings on the involvement of EVs in MPN pathogenesis and discuss opportunities for their potential application as diagnostic and prognostic biomarkers.


Assuntos
Biomarcadores Tumorais/metabolismo , Vesículas Extracelulares/metabolismo , Transtornos Mieloproliferativos/metabolismo , Microambiente Tumoral , Animais , Biomarcadores Tumorais/genética , Vesículas Extracelulares/genética , Vesículas Extracelulares/imunologia , Vesículas Extracelulares/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Mediadores da Inflamação/metabolismo , Transtornos Mieloproliferativos/genética , Transtornos Mieloproliferativos/imunologia , Transtornos Mieloproliferativos/patologia , Policitemia Vera/genética , Policitemia Vera/imunologia , Policitemia Vera/metabolismo , Policitemia Vera/patologia , Mielofibrose Primária/genética , Mielofibrose Primária/imunologia , Mielofibrose Primária/metabolismo , Mielofibrose Primária/patologia , Transdução de Sinais , Trombocitemia Essencial/genética , Trombocitemia Essencial/imunologia , Trombocitemia Essencial/metabolismo , Trombocitemia Essencial/patologia , Microambiente Tumoral/imunologia
14.
Sci Rep ; 11(1): 17702, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34489506

RESUMO

A subset of essential thrombocythemia (ET) cases are negative for disease-defining mutations on JAK2, MPL, and CALR and defined as triple negative (TN). The lack of recurrent mutations in TN-ET patients makes its pathogenesis ambiguous. Here, we screened 483 patients with suspected ET in a single institution, centrally reviewed bone marrow specimens, and identified 23 TN-ET patients. Analysis of clinical records revealed that TN-ET patients were mostly young female, without a history of thrombosis or progression to secondary myelofibrosis and leukemia. Sequencing analysis and human androgen receptor assays revealed that the majority of TN-ET patients exhibited polyclonal hematopoiesis, suggesting a possibility of reactive thrombocytosis in TN-ET. However, the serum levels of thrombopoietin (TPO) and interleukin-6 in TN-ET patients were not significantly different from those in ET patients with canonical mutations and healthy individuals. Rather, CD34-positive cells from TN-ET patients showed a capacity to form megakaryocytic colonies, even in the absence of TPO. No signs of thrombocytosis were observed before TN-ET development, denying the possibility of hereditary thrombocytosis in TN-ET. Overall, these findings indicate that TN-ET is a distinctive disease entity associated with polyclonal hematopoiesis and is paradoxically caused by hematopoietic stem cells harboring a capacity for cell-autonomous megakaryopoiesis.


Assuntos
Hematopoiese Clonal/genética , Megacariócitos , Mutação , Trombocitemia Essencial/genética , Adulto , Fatores Etários , Idoso , Citocinas/sangue , Feminino , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Trombocitemia Essencial/sangue , Trombopoetina/sangue
15.
Hematology ; 26(1): 594-600, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34402416

RESUMO

BACKGROUND: Among myeloproliferative neoplasms, it is often difficult to distinguish essential thrombocythaemia (ET) from prefibrotic-stage primary myelofibrosis (PMF) with thrombocytosis given their overlapping clinicopathological phenotypes. CASE PRESENTATION: We encountered a 45-year-old male who was initially diagnosed with ET and eventually became transformed to secondary myelofibrosis 20 years later. Two distinct types of aberrant megakaryocytes were observed at diagnosis: one type characteristic of ET and the other type characteristic of PMF. With a proliferation in the bone marrow, aberrant megakaryocytes were infiltrated into the extramedullary organs and were even present in the thrombus were observed at autopsy. As a result of next-generation sequencing, the significant increase of variant allele frequency (VAF) of JAK2 V617F and U2AF1 S34Y mutations was observed in the bone marrow cells at the final stage. CONCLUSIONS: This patient could be recognized as an atypical case of aggressive megakaryocytosis transformed from ET.


Assuntos
Megacariócitos/patologia , Mielofibrose Primária/patologia , Trombocitemia Essencial/patologia , Medula Óssea/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Mielofibrose Primária/complicações , Mielofibrose Primária/diagnóstico , Trombocitemia Essencial/complicações , Trombocitemia Essencial/diagnóstico
16.
Lancet Haematol ; 8(9): e658-e665, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34450103

RESUMO

Recommendations regarding management of essential thrombocythaemia rely on studies done before the discovery of the CALR mutation. On May 20, 2020, the European LeukemiaNet annual meeting was held with the goal to identify unmet clinical needs in myeloproliferative neoplasms. Because patients with a CALR mutation have specific clinical characteristics, treatment of CALR-mutated essential thrombocythaemia was considered an unmet clinical need by the European LeukemiaNet. The elaboration of a consensus document with recommendations according to current evidence was proposed as a solution for resolving uncertainties in the treatment of CALR-mutated essential thrombocythaemia. A steering committee comprising four European LeukemiaNet members was then formed and a panel of ten experts in the field was recruited. The experts proposed 51 potential unmet clinical needs in the management of CALR-mutated essential thrombocythaemia and were asked to score the relevance of each topic. Those topics that obtained the highest scores as relevant unmet clinical needs were identified, including antiplatelet therapy in patients at low risk, definition of extreme thrombocytosis and its management in patients at low risk, indications of cytoreduction and targets of therapy, first-line treatment of choice in young patients (<60 years), and management of pregnancy. After the steering committee revised the available evidence for each topic, a consensus on management and proposal for improving knowledge was achieved by use of an email-based, two round, Delphi approach. Consensus was achieved when 90% of the panellists agreed with a statement and included 14 recommendations and six solution proposals. Key recommendations included careful observation for asymptomatic patients with classical, low-risk, CALR-mutated essential thrombocythaemia without cardiovascular risk factors; caution in the use of antiplatelet therapy for symptomatic patients at low risk with platelet counts of 1000-1500 × 109 platelets per L, in such cases cytoreduction is an adequate option, especially if adquired Von Willebrand disease is present; cytoreduction is recommended for extreme thrombocytosis (platelet count >1500 × 109 platelets per L) with pegylated interferon alfa being the preferred option for younger patients; both hydroxycarbamide and anagrelide might be given to patients ineligible for pegylated interferon alfa; and treatment algorithms for patients with high-risk pregnancies should not be changed according to genotype. The European LeukemiaNet proposes to use these recommendations in the routine management of patients with CALR-mutated essential thrombocythaemia, and designing new clinical studies in this field might be useful.


Assuntos
Inibidores da Agregação Plaquetária/uso terapêutico , Trombocitemia Essencial/tratamento farmacológico , Fatores Etários , Calreticulina/genética , Feminino , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Contagem de Plaquetas , Gravidez , Índice de Gravidade de Doença , Trombocitemia Essencial/genética , Trombocitemia Essencial/patologia
17.
Clin J Gastroenterol ; 14(6): 1612-1616, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34342841

RESUMO

Upper gastrointestinal bleeding (UGIB) is a common cause of hospital admission and variceal hemorrhage is responsible for many UGIB cases. Esophageal and gastric varices are caused by portal hypertension (PHT), mostly due to liver cirrhosis. Portal vein thrombosis (PVT) is an important cause of non-cirrhotic PHT and can be associated with several diseases, including myeloproliferative disorders such as essential thrombocythemia (ET). PVT may become apparent due to complications of PHT, including variceal bleeding (VB). We report the case of a 43-year-old male admitted with esophageal VB. Etiologic work-up for chronic liver disease was negative and abdominal magnetic resonance imaging revealed chronic PVT with cavernous transformation and a non-cirrhotic liver. JAK2 mutation was found, and the bone-marrow biopsy was consistent with ET, without peripheral blood alterations. This is a unique case of ET diagnosed in a variceal bleeding setting, remembering the necessity for high clinical suspicion.


Assuntos
Varizes Esofágicas e Gástricas , Hipertensão Portal , Trombocitemia Essencial , Adulto , Varizes Esofágicas e Gástricas/etiologia , Hemorragia Gastrointestinal/etiologia , Humanos , Cirrose Hepática , Masculino , Veia Porta , Trombocitemia Essencial/complicações
18.
Am J Hematol ; 96(11): 1472-1480, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34424575

RESUMO

The current retrospective study involving a total of 1607 patients was designed to identify clinical and molecular variables that were predictive of inferior myelofibrosis-free survival (MFS) in WHO-defined essential thrombocythemia (ET), utilizing three independent patient cohorts: University of Florence, Italy (n = 718); Mayo Clinic, USA (n = 479) and Policlinico Gemelli, Catholic University, Rome, Italy (n = 410). The Florence patient cohort was first examined to identify independent risk factors for MFS, which included age > 60 years (HR 2.5, 95% CI 1.3-4.9), male sex (2.1, 1.2-3.9), palpable splenomegaly (2.1, 1.2-3.9), CALR 1/1-like or MPL mutation (3.4, 1.9-6.1) and JAK2V617F variant allele frequency > 35% (4.2, 1.6-10.8). Subsequently, an operational molecular risk category was developed and validated in the other two cohorts from Mayo Clinic and Rome: "high molecular risk" category included patients with JAK2V617F VAF >35%, CALR type 1/1-like or MPL mutations; all other driver mutation profiles were assigned to "low molecular risk" category. The former, compared to the latter molecular risk category, displayed significantly higher risk of fibrotic transformation: Florence cohort with respective fibrotic transformation risk rates of 8% vs. 1.2% at 10 years and 33% vs. 8% at 20 years (p < 0.001; HR 6.1; 95% CI 3.2-11.7); Mayo Cohort, 16% vs. 7% at 10 years and 44% vs. 25% at 20 years (p < 0.001; HR 2.5; 95% CI 1.6-4.1); and Rome cohort 7.8% vs. 4.6% at 10 years and 31.2% vs. 7.1% at 20 years (p = 0.007, HR 2.7; 95% CI 1.3-5.8). The present study provides practically useful risk signals for fibrotic transformation in ET and facilitates identification of patients who require close monitoring and appropriate counseling.


Assuntos
Trombocitemia Essencial/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Fibrose , Humanos , Janus Quinase 2/genética , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Receptores de Trombopoetina/genética , Estudos Retrospectivos , Trombocitemia Essencial/diagnóstico , Trombocitemia Essencial/genética , Adulto Jovem
19.
Ann Hematol ; 100(11): 2699-2706, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34383101

RESUMO

To assess the effects between MPL and JAK2V617F on the thrombosis risk and peripheral blood cell counts in patients with essential thrombocythemia (ET), we identified eligible studies from PubMed, Embase, and the Cochrane Library. Seven studies were ultimately included in this meta-analysis. All studies reported the peripheral blood cell counts of ET patients, and three of them reported the eligible thrombotic events. In comparing the effect of MPL versus JAK2V617F on thrombosis, 1257 ET patients (73 MPL + and 1184 JAK2V617F +) were included. MPL-positive (MPL +) ET patients had a higher risk of thrombosis than JAK2V617F-positive (JAK2V617F +) ET patients [RR = 1.80 (1.08-3.01), P = 0.025]. And 3453 ET patients (138 MPL + and 3315 JAK2V617F +) were included in the comparison of peripheral blood cell counts. Platelet counts of MPL + ET patients were higher than that of JAK2V617F + ET patients [WMD = 81.18 (31.77-130.60), P = 0.001]. MPL + ET patients had lower hemoglobin [WMD = - 11.66 (- 14.32 to - 9.00), P = 0.000] and white blood cell counts [WMD = - 1.01 (- 1.47 to - 0.56), P = 0.000] than JAK2V617F + ET patients. These findings indicate that the MPL mutation is a high-risk factor for thrombosis in ET patients, and it may be rational to include MPL mutation in the revised IPSET as a criterion for thrombosis prediction scores. And given the differences in peripheral blood, it is necessary to further study whether MPL + ET patients differ from JAK2V617F + ET patients in bleeding and survival.


Assuntos
Contagem de Células Sanguíneas , Janus Quinase 2/genética , Mutação , Receptores de Trombopoetina/genética , Trombocitemia Essencial/genética , Trombose/etiologia , Humanos , Mutação de Sentido Incorreto , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Trombocitemia Essencial/sangue , Trombocitemia Essencial/complicações , Trombose/sangue , Trombose/epidemiologia
20.
J Hematol Oncol ; 14(1): 119, 2021 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-34325728

RESUMO

In a population of 42 Philadelphia negative myeloproliferative neoplasm patients, all on systemic active treatment, the likelihood of responding to anti-SARS-CoV-2 BNT162b2 vaccine at 2 weeks after the second dose was significantly lower in the ten patients with myelofibrosis compared to the 32 with essential thrombocythemia (n = 17) and polycythemia vera (n = 15) grouped together, both in terms of neutralizing anti-SARS-CoV-2 IgG titers and seroprotection rates (32.47 AU/mL vs 217.97 AU/mL, p = 0.003 and 60% vs 93.8%, p = 0.021, respectively). Ruxolitinib, which was the ongoing treatment in five patients with myelofibrosis and three with polycythemia vera, may be implicated in reducing vaccine immunogenicity (p = 0.076), though large prospective study is needed to address this issue.


Assuntos
Anticorpos Antivirais/sangue , Vacinas contra COVID-19/administração & dosagem , COVID-19/tratamento farmacológico , Policitemia Vera/imunologia , Mielofibrose Primária/imunologia , SARS-CoV-2/efeitos dos fármacos , Trombocitemia Essencial/imunologia , Idoso , Anticorpos Antivirais/imunologia , COVID-19/complicações , COVID-19/virologia , Feminino , Humanos , Masculino , Policitemia Vera/patologia , Policitemia Vera/virologia , Mielofibrose Primária/patologia , Mielofibrose Primária/virologia , Prognóstico , Trombocitemia Essencial/patologia , Trombocitemia Essencial/virologia
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