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1.
Lancet Haematol ; 9(1): e38-e48, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34971581

RESUMO

BACKGROUND: Patients with essential thrombocythaemia or polycythaemia vera have several symptoms that can worsen their quality of life. We aimed to assess how symptom burden changes over time with cytoreductive therapy. METHODS: We performed a post-hoc analysis of data from MPN-RC 111-a single-arm, open-label, phase 2, multicentre trial at 17 hospitals and cancer centres in Italy and the USA, evaluating the clinical-haematological response to pegylated interferon alfa-2a in patients who were resistant or intolerant to hydroxyurea (NCT01259817)-and MPN-RC 112-a randomised, open-label, phase 3, multicentre trial at 25 hospitals and cancer centres in France, Germany, Israel, Italy, the UK, and the USA, comparing the clinical-haematological response to pegylated interferon alfa-2a versus hydroxyurea in therapy-naive patients with either high-risk essential thrombocythaemia or polycythaemia vera (NCT01258856). Patients completed the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) and the European Organisation for the Research and Treatment of Cancer Core Quality of Life Questionnaire through 12 months after initiation of treatment as secondary endpoints. In this post-hoc analysis, we examined the association of symptom burden with the clinical-haematological response at 12 months and the effect of baseline symptom burden (ie, high burden [total symptom score ≥20] vs low burden [total symptom score <20]) on subsequent changes in symptoms, estimated via mixed models. A clinically significant improvement in symptom burden was defined as 50% or greater improvement in the MPN-SAF total symptom score from baseline to 12 months in patients with a total symptom score greater than zero at baseline. FINDINGS: 135 patients were enrolled in MPN-RC 111 between Feb 15, 2012, and Dec 23, 2015, and 168 were enrolled in MPN-RC 112 between Sept 24, 2011, and June 30, 2016. For this analysis, we included data from 114 patients from MPN-RC 111 (64 [56%] with essential thrombocythaemia and 50 [44%] with polycythaemia vera; 56 [49%] were female, and 100 [91%] of 110 were white) and 166 patients from MPN-RC 112 (79 [48%] with essential thrombocythaemia and 87 [52%] with polycythaemia vera; 68 [41%] were female, and 145 [93%] of 156 were white). At 12 months, a clinically significant improvement in symptom burden was reported by 12 (32%) of 38 complete responders and seven (20%) of 35 partial responders treated with pegylated interferon alfa-2a in MPN-RC 111; five (19%) of 27 complete responders and six (18%) of 34 partial responders treated with pegylated interferon alfa-2a in MPN-112; and eight (27%) of 30 complete responders and six (22%) of 27 partial responders treated with hydroxyurea in MPN-112. More complete and partial responders reported a clinically significant improvement than did non-responders (44 [22%] of 191 complete and partial responders vs four [5%] of 76 non-responders; Fisher's exact p=0·0003). Symptom burden improved between 3 and 12 months in patients with high baseline symptom burden, both those treated with pegylated interferon alfa-2a (mean total symptom score change -10·2, 95% CI -13·2 to -7·2) and those treated with hydroxyurea (-6·8, -11·2 to -2·4). However, symptom burden worsened between 3 and 12 months in patients with low baseline symptom burden (patients treated with pegylated interferon alfa-2a: mean total symptom score change 3·2, 95% CI 0·9 to 5·4; patients treated with hydroxyurea: 3·4, 0·6 to 6·2). INTERPRETATION: Results can inform treatment decisions, including treatment timing and goals in managing essential thrombocythaemia and polycythaemia vera, because measuring symptom burden from the patient perspective is crucial to understanding treatment efficacy and tolerability. FUNDING: US National Cancer Institute of the National Institutes of Health, and Roche Genentech.


Assuntos
Policitemia Vera , Trombocitemia Essencial , Feminino , Humanos , Hidroxiureia/uso terapêutico , Interferon-alfa , Policitemia Vera/tratamento farmacológico , Polietilenoglicóis , Qualidade de Vida , Proteínas Recombinantes , Trombocitemia Essencial/tratamento farmacológico
3.
Cells ; 10(12)2021 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-34944059

RESUMO

Classical BCR-ABL-negative myeloproliferative neoplasms (MPN) are a heterogeneous group of hematologic malignancies, including essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF), as well as post-PV-MF and post-ET-MF. Progression to more symptomatic disease, such as overt MF or acute leukemia, represents one of the major causes of morbidity and mortality. There are clinically evident but also subclinical types of MPN progression. Clinically evident progression includes evolution from ET to PV, ET to post-ET-MF, PV to post-PV-MF, or pre-PMF to overt PMF, and transformation of any of these subtypes to myelodysplastic neoplasms or acute leukemia. Thrombosis, major hemorrhage, severe infections, or increasing symptom burden (e.g., pruritus, night sweats) may herald progression. Subclinical types of progression may include increases in the extent of bone marrow fibrosis, increases of driver gene mutational allele burden, and clonal evolution. The underlying causes of MPN progression are diverse and can be attributed to genetic alterations and chronic inflammation. Particularly, bystander mutations in genes encoding epigenetic regulators or splicing factors were associated with progression. Finally, comorbidities such as systemic inflammation, cardiovascular diseases, and organ fibrosis may augment the risk of progression. The aim of this review was to discuss types and mechanisms of MPN progression and how their knowledge might improve risk stratification and therapeutic intervention. In view of these aspects, we discuss the potential benefits of early diagnosis using molecular and functional imaging and exploitable therapeutic strategies that may prevent progression, but also highlight current challenges and methodological pitfalls.


Assuntos
Síndromes Mielodisplásicas/genética , Transtornos Mieloproliferativos/diagnóstico , Policitemia Vera/genética , Mielofibrose Primária/genética , Trombocitemia Essencial/genética , Progressão da Doença , Proteínas de Fusão bcr-abl/genética , Humanos , Leucemia/diagnóstico , Leucemia/genética , Leucemia/terapia , Mutação/genética , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/patologia , Síndromes Mielodisplásicas/terapia , Transtornos Mieloproliferativos/genética , Transtornos Mieloproliferativos/terapia , Policitemia Vera/diagnóstico , Policitemia Vera/terapia , Mielofibrose Primária/diagnóstico , Mielofibrose Primária/patologia , Mielofibrose Primária/terapia , Trombocitemia Essencial/diagnóstico , Trombocitemia Essencial/terapia , Trombose/diagnóstico , Trombose/genética , Trombose/patologia
4.
Medicina (Kaunas) ; 57(11)2021 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-34833399

RESUMO

Philadelphia-negative myeloproliferative neoplasms (MPN) are aggressive diseases characterized by clonal proliferation of myeloid stem cells. The clonal process leads to excessive red cells production, platelets production, and bone marrow fibrosis. According to the phenotype, MPN can be classified as polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). MPN patients have shortened survival due to the increased risk of thrombosis, hemorrhages, and transformation to acute myeloid leukemia (AML). Prognosis is variable, with a shorter life expectancy in myelofibrosis. Currently, drug therapy can reduce symptoms, splenomegaly, and risk of thrombosis. Still, some patients can be resistant or intolerant to the treatment. At the same time, allogeneic stem cell transplant (ASCT) is the only treatment modality with the potential to cure the disease. Nevertheless, the ASCT is reserved for high-risk leukemic progression patients due to the risk of treatment-related death and comorbidity. Therefore, there is a need for new drugs that can eradicate clonal hematopoiesis and prevent progression to more aggressive myeloid neoplasms. Thanks to the better understanding of the disease's molecular pathogenesis, many new potentially disease-modifying drugs have been developed and are currently in clinical trials. This review explores the most promising new drugs currently in clinical trials.


Assuntos
Transtornos Mieloproliferativos , Policitemia Vera , Mielofibrose Primária , Trombocitemia Essencial , Trombose , Humanos , Transtornos Mieloproliferativos/tratamento farmacológico , Mielofibrose Primária/tratamento farmacológico , Trombose/etiologia
6.
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
8.
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
9.
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
10.
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
11.
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
12.
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
13.
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
14.
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
15.
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
16.
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
17.
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
18.
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
19.
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
20.
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
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