RESUMO
Essential thrombocythemia is the category of myeloproliferative syndromes, generally characterized by a group of clonal stem cell diseases that present a disturbance in the growth of one or more sets of hematopoietic cells. All long clinical treatment, patients may experience gastrointestinal disorders and other metabolic processes that can lead to weight loss and malnutrition. Cytokine is involved in the control of appetite, digestive, and metabolic processes in the body, it can be assumed that increased stimulation could impair the control of these processes leading to loss of body mass. Effective and systematic nutritional intervention is required to ensure patient compliance with treatment and improved nutritional status.
Assuntos
Desnutrição , Estado Nutricional , Trombocitemia Essencial , Redução de Peso , Humanos , Desnutrição/terapia , Cooperação do Paciente , Trombocitemia Essencial/terapia , Trombocitemia Essencial/dietoterapia , Redução de Peso/fisiologia , Guias de Prática Clínica como AssuntoRESUMO
Introducción: La trombocitemia esencial y la mielofibrosis primaria comparten la presencia de las mutaciones JAK2, CALR y MPL. En total, están presentes en poco más del 90 % de los pacientes con estas enfermedades. Objetivos: Determinar el comportamiento de las mutaciones más frecuentes en los genes MPL y CALR en pacientes cubanos. Métodos: Se realizó un estudio ambispectivo, descriptivo y longitudinal en el Instituto de Hematología e Inmunología de Cuba, entre los años 2010 y 2020. Se incluyeron todos los pacientes con sospecha de trombocitemia esencial y de mielofibrosis primaria con muestras de ADN válidas. Se les identificaron las mutaciones CALR y MPL por PCR en tiempo real. Resultados: De los 53 pacientes estudiados, el 67,9 % fueron diagnosticados con trombocitemia esencial, el 22,6 % con mielofibrosis primaria. En el 90,6 % se pudo detectar alguna de las mutaciones conductoras; el 67,9 % fueron positivos a la mutación JAK2V617F, el 13,2 % a las mutaciones en el gen que codifica para la calreticulina y en el 9,4 % se identificaron mutaciones en el gen MPL. Conclusiones: El comportamiento de las mutaciones conductoras JAK2V617F, CALR y MPL en la muestra de pacientes cubanos con trombocitemia esencial y mielofibrosis primaria estuvo en correspondencia con lo descrito en la mayoría de las investigaciones.
Introduction: Essential thrombocythemia and primary myelofibrosis share the presence of JAK2, CALR and MPL mutations. In total, they comprise slightly more than 90 % of patients with these diseases. Objectives: To determine the behavior of the most frequent mutations in MPL and CALR genes in Cuban patients. Methods: An ambispective, descriptive and longitudinal study was performed at the Institute of Hematology and Immunology of Cuba, between 2010 and 2020. All patients with suspected essential thrombocythemia and primary myelofibrosis with valid DNA samples were included. CALR and MPL mutations were identified by real-time PCR. Results: Of the 53 patients studied, 67.9% were diagnosed with essential thrombocythemia, and 22.6% with primary myelofibrosis. In 90.6% it was possible to detect any of the driver mutations: 67.9% were positive for the JAK2V617F mutation, 13.2% for mutations in the gene coding for calreticulin and in 9.4% mutations in the MPL gene were identified. Conclusions: The behavior of the driver mutations JAK2V617F, CALR and MPL in the sample of Cuban patients with essential thrombocythemia and primary myelofibrosis was in correspondence with what is described in the majority of the investigations.
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Resumen ANTECEDENTES: La coexistencia de neoplasias mieloproliferativas durante el embarazo puede derivar en complicaciones para la madre y el feto, de ahí la indispensable necesidad de detectarlas oportunamente. CASO CLÍNICO: Paciente de 30 años, primigesta. En el control prenatal se detectó una elevación significativa de plaquetas y leucocitos. Luego de descartar un proceso infeccioso e interconsulta con el hematólogo se le indicó un antiagregante plaquetario. El embarazo transcurrió sin complicaciones de tipo trombótico o hemorrágico y finalizó mediante cesárea a las 40 semanas, indicada por falta de progresión del trabajo de parto. Posteriormente se inició el tratamiento específico para la enfermedad y seguimiento. METODOLOGÍA: La búsqueda de artículos publicados durante los últimos 20 años se efectuó en las bases de datos PubMed y Clínical Key con los MeSH "essential thrombocytemia AND pregnancy", "hematological neoplasms AND pregnancy". RESULTADOS: Se obtuvieron 14 artículos de los que se excluyeron 3 por no incluir a mujeres embarazadas. La revisión final fue de 11 artículos. CONCLUSIONES: El seguimiento correcto del control prenatal permite advertir las complicaciones médicas independientes del embarazo. Cuando así sucede es posible la intervención oportuna y la participación de otros especialistas que confirmen el diagnóstico para, en conjunto, tomen la mejor decisión en beneficio de la madre y su hijo por nacer.
Abstract BACKGROUND: The coexistence of myeloproliferative neoplasms during pregnancy may lead to maternal and fetal complications, and early detection is essential. CLINICAL CASE: A 30-year-old primigravida. Prenatal examination revealed a significant increase in platelets and leukocytes. After exclusion of an infectious process and consultation with the haematologist, she was prescribed an antiplatelet agent. The pregnancy proceeded without thrombotic or haemorrhagic complications and was terminated by caesarean section at 40 weeks, indicated for lack of progress in labour. Specific treatment of the disease and follow-up were then initiated. METHODOLOGY: Articles published in the last 20 years were searched in PubMed and Clinical Key databases using MeSH "essential thrombocythemia AND pregnancy", "haematological neoplasms AND pregnancy". RESULTS: We obtained 14 articles, of which 3 were excluded because they did not include pregnant women. The final review consisted of 11 articles. CONCLUSIONS: Correct follow-up of antenatal care can warn of medical complications independent of pregnancy. In this case, timely intervention and involvement of other specialists is possible to confirm the diagnosis and make the best joint decision for the benefit of the mother and her unborn child.
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Introducción: La trombocitemia esencial es una neoplasia mieloproliferativa crónica caracterizada por una trombocitosis mantenida en sangre periférica y una hiperplasia de megacariocitos maduros en médula ósea, con características histológicas y moleculares específicas. Objetivo: Caracterizar los pacientes adultos con trombocitemia esencial en el Instituto de Hematología e Inmunología. Métodos: Se realizó un estudio observacional, descriptivo, longitudinal y retrospectivo. El universo estuvo conformado por 40 pacientes adultos con trombocitemia esencial diagnosticados y tratados con trombocitemia esencial, en el Instituto de Hematología e Inmunología desde enero del 2010 hasta enero del 2020. Los datos se almacenaron en una base de datos confeccionada con el programa SPSS v.25.0 para Windows, a partir de la cual fueron procesados. Resultados: El promedio de edad al diagnóstico fue 52,2 años y una mediana de 51 años. El 80 % correspondió al sexo femenino y el 62,5 % de los pacientes tenían el color de la piel blanca. El 85 % de los pacientes presentaron recuento de plaquetas en el rango entre 450-1500 ( 109/L. El 52,1 % de los casos presentó aumento de la enzima lactato deshidrogenasa y la mutación del JAK2V617F representó el 67,5 %. La supervivencia global en años fue 35,5 y la supervivencia libre de enfermedad fue 32,5 años. Conclusiones: Los pacientes adultos con trombocitemia esencial tienen una supervivencia global y libre de enfermedad significativamente elevada, con baja incidencia de eventos trombóticos y el tratamiento empleado de primera línea se relacionó con la respuesta hematológica estable de los pacientes.
Introduction: Essential thrombocythemia is a chronic myeloproliferative neoplasm characterized by thrombocytosis maintained in peripheral blood and hyperplasia of mature megakaryocytes in bone marrow, with specific histological and molecular characteristics. General: To characterize of adult patients with essential thrombocythemia in the Institute of Hematology and Immunology. Methods: An observational, descriptive, longitudinal and retrospective study was conducted. The universe consisted of 40 adult patients diagnosed and treated with essential thrombocythemia at the Institute of Hematology and Immunology from January 2010 to January 2020. The data obtained were stored in a database made with the program SPSS v 25.0 for Windows, from which they were processed. Results: The average age at diagnosis was 52,2 years and a median of 51 years. 80% occurred in females and 62,5% of patients were white. 85% of the patients had platelet counts in therange between 450-1500 ( 109/L. An increase in the enzyme lactate dehydrogenase was observed in 52,1% of the cases, and the JAK2V617Fmutationaccountedfor 67,5%. The overall survival in years was 35,5 and the disease-free survival was 32.5 years. Conclusions: Adult patients with essential thrombocythemia have significantly increased overall and disease-free survival, with low incidence of thrombotic events and first-line treatment was associated with stable hematological response of patients.
Assuntos
HumanosRESUMO
Introducción: La frecuencia de la mutación JAK2V617F se estima entre el 50 y 60 por ciento en pacientes con trombocitemia esencial y mielofibrosis primaria. El 30 por ciento de los pacientes con policitemia vera y mielofibrosis primaria. Entre 2-4 por ciento de los pacientes con trombocitemia esencial presentan pérdida de heterocigosidad. Objetivos: Evaluar la influencia de la carga alélica de la mutación JAK2V617F y su relación con variables clínico-hematológicas en el diagnóstico de estas enfermedades en pacientes cubanos. Métodos: Se realizó un estudio retrospectivo, descriptivo y longitudinal en el Instituto de Hematología e Inmunología entre 2010 y 2020. Se incluyeron todos los pacientes con sospecha de trombocitemia esencial y mielofibrosis primaria con muestras de ADN válidas. Se les cuantificó la carga alélica de la mutación por PCR en tiempo real. Resultados: Se detectó la mutación en 66,7 por ciento de los diagnosticados con trombocitemia esencial y mielofibrosis primaria. El 62,5 por ciento de los pacientes con mielofibrosis primaria fueron homocigotos a la mutación, mientras que en la trombocitemia esencial solo el 20,8 por ciento. La diferencia de medias de cargas alélicas entre ambas enfermedades fue estadísticamente significativa. No se encontraron diferencias significativas en la comparación de las variables clínicas y hematológicas en estas enfermedades ni asociación con la carga alélica con excepción de las plaquetas en la mielofibrosis primaria. Conclusiones: El estudio estuvo limitado por la escasa muestra de pacientes, pero se corresponde con otras investigaciones que sostienen el concepto de que la presentación fenotípica de las neoplasias mieloproliferativasestá influenciada por la carga mutacional del JAK2V617F(AU)
Introduction: The frequency of the JAK2V617F mutation is estimated to be between 50 percent and 60 percent in patients with essential thrombocythemia and primary myelofibrosis. 30 percent of patients with polycythemia vera and primary myelofibrosis and 2-4 percent of patients with essential thrombocythemia show loss of heterozygosity. Objectives: To evaluate the influence of the allelic load of the JAK2V617F mutation in the diagnosis of these diseases in Cuban patients and its relationship with clinical-hematological variables. Methodology: A retrospective, descriptive and longitudinal study was carried out at the Institute of Hematology and Immunology between 2010 and 2020. All patients with suspected essential thrombocythemia and primary myelofibrosis with valid DNA samples were included. The allelic load of the mutation was quantified by real-time PCR. Results: The mutation was detected in 66.7 percent of those diagnosed with essential thrombocythemia and primary myelofibrosis. 62.5 percent of the patients with primary myelofibrosis were homozygous for the mutation, while in essential thrombocythemia only 20.8 percent. The difference in mean allelic loads between both diseases was statistically significant. No significant differences were found in the comparison of clinical and hematological variables in these diseases or association with allelic load, with the exception of platelets in primary myelofibrosis. Conclusions: The study was limited by the small sample of patients, but it corresponds to other investigations that support the concept that the phenotypic presentation of myeloproliferative neoplasms is influenced by the mutational load of JAK2V617F(AU)
Assuntos
HumanosRESUMO
Essential thrombocythemia (ET) is a chronic Philadelphia-negative myeloproliferative neoplasm that has its main involvement in the megakaryopoietic lineage, generating sustained thrombocytosis in peripheral blood and an increase in the number of mature megakaryocytes in the bone marrow. In addition to marked thrombocytosis, it is characterized by increased thrombotic or hemorrhagic risk and the presence of constitutional symptoms. Patients with ET have a low but known risk of disease progression to myelofibrosis and/or acute leukemia. The diagnosis is made based on the 2016 WHO criteria. At present, available treatments for patients with ET are mainly aimed at minimizing the risk of thrombosis and/or bleeding.
La trombocitemia esencial (TE) es una neoplasia mieloproliferativa crónica Filadelfia negativa que tiene su principal involucro en la línea megacariopoyética, generando trombocitosis sostenida en la sangre periférica y un incremento en el número de megacariocitos maduros en médula ósea. Además de una marcada trombocitosis, se caracteriza por un mayor riesgo trombótico o hemorrágico y la presencia de síntomas constitucionales. Los pacientes con TE tienen un riesgo bajo, pero conocido, de evolución de la enfermedad a mielofibrosis y/o leucemia aguda. El diagnóstico se realiza con base en los criterios de la Organización Mundial de la Salud del 2016. Los tratamientos actualmente disponibles para los pacientes con TE están dirigidos principalmente a minimizar el riesgo de trombosis y/o hemorragia.
RESUMO
La trombocitemia esencial forma parte del grupo de neoplasias mieloproliferativas. Se caracteriza por síntomas microvasculares y vasomotores, recuento plaquetario superior a 450 x 109/l, proliferación megacariocítica con morfología grande y madura, ausencia de proliferación eritroide y granulocítica, demostración de JAK2V617F u otro marcador clonal y ausencia de evidencia de trombocitosis reactiva. Se reporta el manejo anestésico en una paciente donde las principales consideraciones están relacionadas con la prevención de eventos hemorrágicos y trombóticos. La suspensión de la aspirina, el mantenimiento del tratamiento con hidroxiurea, la preparación con ácido tranexámico, el uso pre y posoperatorio de fraxiparina, hidratación adecuada, uso de medias elásticas en miembros inferiores, deambulación precoz, buena hemostasia quirúrgica y disponibilidad de concentrados de plaquetas son los elementos fundamentales en la conducción anestésica de esta paciente(AU)
Essential thrombocythemia is part of the group of myeloproliferative neoplasms. It is characterized by microvascular and vasomotor symptoms, platelet count over 450x109/L, megakaryocytic proliferation with large and mature morphology, absence of erythroid and granulocytic proliferation, demonstration of JAK2V617F or other clonal marker, and absence of evidence of reactive thrombocytosis. Anesthetic management is reported in a patient, whose case's main considerations are related to the prevention of hemorrhagic and thrombotic events. Aspirin suspension, maintenance of hydroxyurea treatment, preparation with tranexamic acid, pre- and post-operative use of fraxiparin, adequate hydration, use of elastic stockings in lower limbs, early ambulation, good surgical hemostasis, as well as availability of platelet concentrates are the fundamental elements in the anesthetic management of this patient(AU)
Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Contagem de Plaquetas , Trombocitemia Essencial/complicações , Hemostasia Cirúrgica , Ácido Tranexâmico/uso terapêutico , Meias de Compressão , Anestésicos/uso terapêuticoRESUMO
INTRODUCTION AND IMPORTANCE: Essential thrombocythemia (ET) is a myeloproliferative disorder characterized by increased platelet count and a high risk of bleeding or thrombotic events due to platelet dysfunction. Patients with ET are treated according to their risk of complications with cytoreductive or anti-aggregant treatment. Neither guidelines for oncologic patients nor perioperative management of patients with ET have been determined. CASE PRESENTATION: A 41-year-old female patient with ET who had alternating constipation and diarrhea was referred after a screening colonoscopy diagnosing a locally advanced rectosigmoid junction colon adenocarcinoma with liver metastases. Systemic preoperative chemotherapy was indicated. The patient underwent laparoscopic low anterior resection plus volume-preserving right lobectomy of the liver. Postoperative bleeding of the internal iliac artery (IIA) associated with hematoma at the lower pelvic cavity was diagnosed and treated by interventional radiology; the patient was discharged without other complications 16 days after surgery. CLINICAL DISCUSSION: ET has been related to the development of hematologic complications or second non-hematologic malignancies. A systematic review was conducted to seek guidance for the management of such patients in the perioperative period. Special perioperative care must be taken, and complications management should avoid further hemorrhages or cloth formation. CONCLUSION: Under oncologic and hematological guidance, minimally invasive surgery and non-invasive management of complications are advised in the lack of published perioperative management guidelines of ET patients with colorectal cancer.
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RESUMEN La transformación cavernomatosa de vena porta es una condición caracterizada por la formación de una red de venas colaterales dilatadas a lo largo de una vena porta previamente trombosada. Es considerada una entidad de baja frecuencia y se presenta más comúnmente en población pediátrica. Presentamos el caso de una mujer adulta con diagnóstico de transformación cavernomatosa de vena porta, originado como consecuencia de una trombocitemia esencial oculta. Como medida terapéutica a la hipertensión portal se realizó una ligadura endoscópica de várices gastroesofágicas en múltiples oportunidades sin resultados positivos. No se practicó derivación portosistémica por la presencia de abundantes colaterales. Finalmente, se realizó una esplenectomía, posterior a lo cual se logró evidenciar una trombocitemia esencial. La paciente evolucionó con múltiples complicaciones médico-quirúrgicas, que la llevaron a una falla multisistémica y posterior fallecimiento. No existen datos de prevalencia regional ni se han reportado casos de transformación cavernomatosa de vena porta asociado a trombocitemia esencial por lo que consideramos de gran importancia dar a conocer este caso, de modo a poder ayudar a establecer con mayor precisión y rapidez el diagnóstico y tratamiento de esta rara entidad.
ABSTRACT Cavernous transformation of the portal vein is a condition characterized by the formation of a network of dilated collateral veins along a previously thrombosed portal vein. It is considered a low-frequency entity and occurs more commonly in the pediatric population. We present the case of an adult woman with a diagnosis of cavernous transformation of the portal vein, originated as a consequence of occult essential thrombocythemia. As a therapeutic measure for portal hypertension, endoscopic ligation of gastroesophageal varices was performed on multiple occasions without positive results. Portosystemic bypass was not performed due to the presence of abundant collaterals. Finally, a splenectomy was performed, after which essential thrombocythemia was evidenced. The patient evolved with multiple medical-surgical complications, which led to multisystem failure and subsequent death. There are no regional prevalence data, nor have there been reports of cavernous transformation of the portal vein associated with essential thrombocythemia, for which reason we consider of great importance to make this case known, in order to help establish the diagnosis and treatment of this rare entity with greater precision and speed.
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Patients with Essential Thrombocythemia pose a variety of anesthetic challenges including a heightened risk of perioperative thrombosis. This condition is also associated with perioperative hemorrhage, risk for developing heparin induced thrombocytopenia type 2 during cardiac surgery and digital gangrene from radial artery catheterization.
Los pacientes con trombocitemia esencial plantean una variedad de desafíos anestésicos, incluido un mayor riesgo de trombosis perioperatoria. Esta condición también se asocia con hemorragia perioperatoria, riesgo de desarrollar trombocitopenia tipo 2 inducida por heparina durante la cirugía cardíaca y gangrena digital por cateterismo de la arteria radial.
Assuntos
Humanos , Trombocitopenia , Trombose , Cateterismo , Trombocitemia Essencial , Cirurgia Torácica , Artéria Radial , Hemorragia , AnestésicosRESUMO
Essential thrombocythemia (ET) is comprised among chronic myeloproliferative neoplasms (MPN) and is caused by driver mutations in JAK2, CALR, and MPL, which lead to megakaryocyte proliferation and prominent thrombocytosis. Thrombosis remains the main cause of morbidity in ET and is driven by the interplay between blood cells, the endothelium, the clotting cascade, and host-derived inflammatory mediators. Platelet activation plays a key role in the thrombotic predisposition, although the underlying mechanisms remain poorly defined. In addition to their role in hemostasis, platelets participate in innate immunity and inflammation owing to the expression of toll-like receptors (TLR), which recognize inflammatory signals, triggering platelet functional responses. Considering the impact of inflammation on ET procoagulant state, we assessed the contribution of TLR2 and TLR4 to platelet hemostatic and inflammatory properties in ET patients, by using Pam3CSK4 and lipopolysaccharide (LPS) as specific TLR2 and TLR4 ligands, respectively. TLR2 ligation induced increased surface translocation of α-granule-derived P-selectin and CD40L, which mediate platelet interaction with leukocytes and endothelial cells, respectively, and higher levels of dense granule-derived CD63 in patients, whereas PAC-1 binding was not increased and LPS had no effect on these platelet responses. Platelet-neutrophil aggregate formation was elevated in ET at baseline and after stimulation of both TLR2 and TLR4. In addition, ET patients displayed higher TLR2- and TLR4-triggered platelet secretion of the chemokine RANTES (CCL5), whereas von Willebrand factor release was not enhanced, revealing a differential releasate pattern for α-granule-stored inflammatory molecules. TLR-mediated hyperresponsiveness contrasted with impaired or preserved responses to classic platelet hemostatic agonists, such as TRAP-6 and thrombin. TLR2 and TLR4 expression on the platelet surface was normal, whereas phosphorylation of downstream effector ERK1/2 was higher in patients at baseline and after incubation with Pam3CSK4, which may partly explain the enhanced TLR2 response. In conclusion, exacerbated response to TLR stimulation may promote platelet activation in ET, boosting platelet/leukocyte/endothelial interactions and secretion of inflammatory mediators, overall reinforcing the thromboinflammatory state. These findings highlight the role of platelets as inflammatory sentinels in MPN prothrombotic scenario and provide additional evidence for the close intertwining between thrombosis and inflammation in this setting.
Assuntos
Plaquetas/fisiologia , Inflamação/etiologia , Trombocitemia Essencial/complicações , Trombose/etiologia , Receptores Toll-Like/fisiologia , Adulto , Idoso , Quimiocina CCL5/fisiologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neutrófilos/fisiologia , Fosforilação , Ativação Plaquetária , Trombocitemia Essencial/imunologiaRESUMO
BACKGROUND: Research into Philadelphia-negative chronic myeloproliferative neoplasms is heterogeneous. In addition, no systematization of studies of polycythemia vera (PV), essential thrombocythemia (ET) or primary myelofibrosis (PMF) have been carried out. The objective of this review is to characterize studies on BCR-ABL1-negative chronic myeloproliferative neoplasms and to compare the frequency of JAK2, MPL and CALR mutations in PV, ET and PMF. METHOD: A systematic review of the scientific literature was conducted, as was meta-analysis with an ex-ante selection of protocol, according to phases of the PRISMA guide in three interdisciplinary databases. To guarantee reproducibility in the pursuit and retrieval of information, the reproducibility and methodological quality of the studies were evaluated by two researchers. RESULTS: Fifty-two studies were included, the majority having been carried out in the United States, China, Brazil and Europe. The frequency of the JAK2V617F mutation ranged from 46.7 to 100% in patients with PV, from 31.3 to 72.1% in patients with ET, and from 25.0 to 85.7% in those with PMF. The frequency of the MPL mutation was 0% in PV, from 0.9 to 12.5% in ET, and from 0 to 17.1% in PMF. The CALR mutation occurred at a frequency of 0.0% in PV, whereas in ET, it ranged from 12.6 to 50%, and in PMF, it ranged from 10 to 100%. The risk of this mutation presenting in PV is 3.0 times that found for ET and 4.0 times that found for PMF. CONCLUSION: Given the specificity and reported high frequencies of the JAK2V617F, MPL and CALR mutations in this group of neoplasms, the diagnosis of these diseases should not be made on clinical and hematological characteristics alone but should include genetic screening of patients.
Assuntos
Calreticulina/genética , Janus Quinase 2/genética , Taxa de Mutação , Policitemia Vera/genética , Mielofibrose Primária/genética , Receptores de Trombopoetina/genética , Trombocitemia Essencial/genética , Biomarcadores Tumorais/genética , Heterogeneidade Genética , Testes Genéticos , Humanos , Proteínas de Fusão Oncogênica/genética , Reprodutibilidade dos TestesRESUMO
Resumen Introducción: la carga sintomática de pacientes con neoplasias mieloproliferativas crónicas Filadélfia negativas (NMC-PhN) afecta la calidad de vida (CV). Existen escalas para evaluar la magnitud de los síntomas, una de ellas, MPN-SAF-10. En nuestra región existe escasa información sobre CV de pacientes con NMC-PhN. Objetivos: estimar el puntaje de calidad de vida con la escala MPN-SAF-10 en pacientes con NMC-PhN atendidos en el Hospital de San José (Bogotá, Colombia) y explorar asociaciones entre el tiempo de tratamiento, carga de complicaciones y el efecto en la CV. Material y métodos: estudio de corte transversal analítico para evaluar CV basada en carga sintomática de pacientes con NMC-PhN del Hospital de San José (Bogotá, Colombia). Se realizó análisis descriptivo y estratificado de calidad de vida, tratamiento citorreductor y de diferentes complicaciones, así como pruebas de asociación de los puntajes de riesgo de cada enfermedad con sus respectivos puntajes de CV. Resultados: en 64 pacientes la escala MPN-SAF-10 documentó medianas de puntajes globales de CV de 3 (RIC 1-6), MPN-SAF-10 de 20 (RIC 8-32). Un 49% de los pacientes tuvo algún grado de alteración (30% moderada y 19% severa), sin diferencias entre las tres enfermedades. Los puntajes de CV no variaron entre las NMC-PhN. El tratamiento y duración del mismo no se correlacionaron con la escala de MPN-SAF-10 (hidroxiúrea r: - 0.27; ruxolitinib r: 0.12). Conclusiones: en pacientes con NMC-PhN, la evaluación de CV con la escala MPN-SAF-10 evidencia algún grado de afectación a pesar del tratamiento; ésta es útil para objetivar dicha afectación y debe implementarse en la práctica clínica. (Acta Med Colomb 2019; 44: 82-90).
Abstract Introduction: the symptomatic burden of patients with Philadelphia negative chronic myelopro liferative neoplasms (NMC-PhN) affects the quality of life (QL). There are scales to evaluate the magnitude of the symptoms; one of them, MPN-SAF-10. In our region there is scarce information on QL of patients with NMC-PhN. Objectives: To estimate the quality of life score with the MPN-SAF-10 scale in patients with NMC-PhN treated at Hospital de San José (Bogotá, Colombia) and to explore associations between treatment time, complication load and the effect on the QL. Material and methods: Analytical cross-sectional study to evaluate QL based on symptomatic load of patients with NMC-PhN from Hospital de San José (Bogotá, Colombia). A descriptive and stratified analysis of quality of life, cytoreductive treatment and different complications was carried out, as well as association tests of the risk scores of each disease with their respective QL scores. Results: in 64 patients the MPN-SAF-10 scale documented medians of global QL scores of 3 (RIC 1-6), MPN-SAF-10 of 20 (RIC 8-32). 49% of the patients had some degree of alteration (30% moderate and 19% severe), without differences between the three diseases. The QL scores did not vary between the NMC-PhN. The treatment and its duration did not correlate with the MPN-SAF-10 scale (Hydroxyurea r: - 0.27, Ruxolitinib r: 0.12). Conclusions: in patients with NMC-PhN, the evaluation of QL with the MPN-SAF-10 scale shows some degree of affectation despite the treatment; this is useful to objectify this affectation and should be implemented in clinical practice. (Acta Med Colomb 2019; 44: 82-90).
Assuntos
Humanos , Masculino , Feminino , Adulto , Doenças Mieloproliferativas-Mielodisplásicas , Policitemia Vera , Qualidade de Vida , Mielofibrose Primária , Trombocitemia EssencialRESUMO
The genetic events associated with transformation of myeloproliferative neoplasms (MPNs) to secondary acute myeloid leukemia (sAML), particularly in the subgroup of essential thrombocythemia (ET) patients, remain incompletely understood. Deep studies using high-throughput methods might lead to a better understanding of genetic landscape of ET patients who transformed to sAML. We performed array-based comparative genomic hybridization (aCGH) and whole exome sequencing (WES) to analyze paired samples from ET and sAML phases. We investigated five patients with previous history of MPN, which four had initial diagnosis of ET (one case harboring JAK2 p.Val617Phe and the remaining three CALR type II p.Lys385fs*47), and one was diagnosed with MPN/myelodysplastic syndrome with thrombocytosis (SF3B1 p.Lys700Glu). All were homogeneously treated with hydroxyurea, but subsequently transformed to sAML (mean time of 6 years/median of 4 years to transformation). Two of them have chromosomal abnormalities, and both acquire 2p gain and 5q deletion at sAML stage. The molecular mechanisms associated with leukemic progression in MPN patients are not clear. Our WES data showed TP53 alterations recurrently observed as mutations (missense and frameshift) and monoallelic loss. On the other hand, aCGH showed novel chromosome abnormalities (+2p and del5q) potentially associated with disease progression. The results reported here add valuable information to the still fragmented molecular basis of ET to sAML evolution. Further studies are necessary to identify minimal deleted/amplified region and genes relevant to sAML transformation.
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OBJECTIVES: To establish the frequency of JAK2, MPL and CALR mutations in Argentinean patients with BCR-ABL1-negative myeloproliferative neoplasms (MPN) and to compare their clinical and haematological features. METHODS: Mutations of JAK2V617F, JAK2 exon 12, MPL W515L/K and CALR were analysed in 439 Argentinean patients with BCR-ABL1-negative MPN, including 176 polycythemia vera (PV), 214 essential thrombocythemia (ET) and 49 primary myelofibrosis (PMF). RESULTS: In 94.9% of PV, 85.5% ET and 85.2% PMF, we found mutations in JAK2, MPL or CALR. 74.9% carried JAK2V617F, 12.3% CALR mutations, 2.1% MPL mutations and 10.7% were triple negative. In ET, nine types of CALR mutations were identified, four of which were novel. PMF patients were limited to types 1 and 2, type 2 being more frequent. DISCUSSION: In ET, patients with CALR mutation were younger and had higher platelet counts than those with JAK2V617F and triple negative. In addition, JAK2V617F patients had high leucocyte and haemoglobin values compared with CALR-mutated and triple-negative patients. In PMF, patients with mutant CALR were associated with higher platelet counts. CONCLUSION: Our study underscores the importance of JAK2, MPL and CALR genotyping for accurate diagnosis of patients with BCR-ABL1-negative MPN.
Assuntos
Calreticulina/genética , Proteínas de Fusão bcr-abl/genética , Janus Quinase 2/genética , Mutação , Transtornos Mieloproliferativos/genética , Receptores de Trombopoetina/genética , Idoso , Argentina , Calreticulina/metabolismo , Feminino , Proteínas de Fusão bcr-abl/metabolismo , Humanos , Janus Quinase 2/metabolismo , Masculino , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/sangue , Transtornos Mieloproliferativos/metabolismo , Receptores de Trombopoetina/metabolismoRESUMO
Resumen Introducción y objetivos: las neoplasias mieloproliferativas crónicas (NMPC) son relativamente raras, con incidencias que varían entre 0.47-1.03/100 000 habitantes. Se presenta el primer informe del trabajo del registro colombiano de NMPC, cuyo objetivo es describir las características clínicas de estos pacientes en nuestro país. Material y métodos: estudio descriptivo observacional, multicéntrico, retrospectivo y prospectivo en ocho centros del país, de abril de 2013 a diciembre de 2014. Las variables cualitativas se presentan con frecuencias absolutas y relativas; y las cuantitativas se resumen en medidas de tendencia central y dispersión. Resultados: once centros fueron aprobados, ocho ingresaron pacientes. En los primeros 179 casos reportados, 50% eran hombres, la edad promedio al diagnóstico 58.7 años (rango 19-92). Noventa y tres muestran trombocitemia esencial (TE); 55, policitemia vera (PV); y 31, mielofibrosis (MF). El 41% tenía esplenomegalia al diagnóstico; el 20% tuvo complicaciones trombóticas; y 12.85%, sangrado. Sólo en 57.5% se realizó JAK; de ellos, en 53.5% fue positivo, en especial sólo 60% de las PV. El 8% de los casos no tenía estudio de médula ósea, el 29.3% tiene algún grado de fibrosis. El hallazgo más frecuente fue hiperplasia megacariocítica en 59.78%. Más de 50% de pacientes estaban sintomáticos al diagnóstico. Sólo el 11% no recibió tratamiento farmacológico; los más frecuentes fueron hidroxiurea en 149 casos y ASA en 79. Con promedio de seguimiento de 52.6 meses; el 97.21% de los pacientes están vivos. Conclusiones: los hallazgos sugieren que algunas características de las NMPC podrían ser diferentes a lo reportado en otras series, lo que valida la importancia del esfuerzo de recoger información local.
Abstract Introduction and objectives: chronic MPNs are relatively rare, with incidences varying between 0.47-1.03 / 100 000 inhabitants. The first report of the work of the Colombian registry of chronic MPNs, whose objective is to describe the clinical characteristics of these patients in our country, is presented. Materials and methods: descriptive observational, multicenter, retrospective and prospective study in eight centers of the country, from April 2013 to December 2014. Qualitative variables are presented with absolute and relative frequencies, and the quantitative ones are summarized in measures of central tendency and dispersion. Results: eleven centers were approved; 8 admitted patients. In the first 179 cases reported, 50% were men; the average age at diagnosis was 58.7 years (range 19-92). Ninety-three present essential thrombocythemia (ET); 55, polycythemia vera (PV); and 31, myelofibrosis (MF). 41% had splenomegaly at diagnosis; 20% had thrombotic complications, and 12.85%, bleeding. JAK was performed in only 57.5%. Of them, in 53.5% was positive, especially in only 60% of the PV. 8% of the cases had no bone marrow study; 29.3% had some degree of fibrosis. The most frequent finding was megakaryocytic hyperplasia in 59.78%. More than 50% of patients were symptomatic at diagnosis. Only 11% did not receive pharmacological treatment, being the most frequent hydroxyurea in 149 cases and ASA in 79, with an average follow-up of 52.6 months. 97.21% of patients are alive. Conclusions: the findings suggest that some characteristics of chronic MPNs could be different from those reported in other series, which validates the importance of the effort to collect local information.
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Humanos , Masculino , Feminino , Transtornos Mieloproliferativos , Policitemia Vera , Sistema de Registros , Mielofibrose Primária , Trombocitemia Essencial , MutaçãoRESUMO
BACKGROUND: Essential thrombocythemia (ET) is a benign disease with slow progress in which thrombosis is a cause of mortality. JAK2V617F and calreticulin (CALR) are the most frequent mutations in this disease. In this systematic review and meta-analysis, we compared the prevalence of JAK2V617F and CALR mutations in ET and examined the incidence of thrombosis and other hematologic indices. METHODS: After choosing MeSH keywords, including essential thrombocythemia, JAK2V617F, calreticulin, prognosis, and diagnosis, as well as searching Medline/PubMed and Scopus, 12 papers were selected. Data were pooled, and summary prevalence and OR were estimated using either a random-effects model or a fixed-effects model. RESULTS: The frequency of JAK2V617F and CALR shows heterogeneity in Caucasian population [JAK2V617 I 2% = 84.3, P < 0.001, 95% CI 0.56 (0.51-0.61)], [CALR I 2% = 96.1, P < 0.001, 95% CI 0.23 (0.15-0.31)]. The prevalence of JAK2V617F and CALR was 0.57 (95% CI 0.53-0.61), I 2% = 79.3 and 0.22 (95% CI 0.16-0.27), I 2% = 94, respectively. JAK2V617F positive ET was associated with increasing odds of thrombosis [OR 2.35 (95% CI 1.83-3.02), P < 0.001]. The incidence of splenomegaly was not statistically different between these two mutations. Hemoglobin, platelet, and WBC count did not affect the risk of thrombosis. CONCLUSIONS: Detection of CALR mutation is helpful for molecular diagnosis of ET patients as well as JAK2V617F. Due to reduction of thrombosis in CALR-positive patients, it can be stated that such patients have less thrombotic disorders and better prognosis relative to patients bearing JAK2V617F mutation. Therefore, detection of mutation in CALR and JAK2V617F may contribute to diagnosis and prognosis of ET patients.
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Calreticulina/genética , Janus Quinase 2/genética , Mutação , Trombocitemia Essencial/diagnóstico , Trombocitemia Essencial/genética , Humanos , PrognósticoRESUMO
Summary Introduction: In patients with essential thrombocythemia (ET), the vascular complications contribute to morbidity and mortality. To better predict the occurrence of thrombotic events, an International Prognostic Score for Thrombosis in Essential Thrombocythemia (IPSET-thrombosis) has recently been proposed. We present the application of this score and compare its results with the usual classification system. Method: We retrospectively evaluated the characteristics and risk factors for thrombosis of 46 patients with a diagnosis of ET seen in the last 6 years at Faculdade de Medicina do ABC (FMABC). Results: Thrombosis in the arterial territory was more prevalent than in venous sites. We observed that cardiovascular risk factors (hypertension, hypercholesterolemia, diabetes mellitus, and smoking) were also risk factors for thrombosis (p<0.001). Age over 60 years and presence of JAK2 V617F mutation were not associated with the occurrence of thrombotic events. No patient classified by IPSET-thrombosis as low risk had a thrombotic event. Furthermore, using the IPSET-thrombosis scale, we identified two patients who had thrombotic events during follow-up and were otherwise classified in the low-risk group of the traditional classification. Leukocytosis at diagnosis was significantly associated with arterial thrombosis (p=0.02), while splenomegaly was associated with venous thrombotic events (p=0.01). Conclusion: Cardiovascular risk factors and leukocytosis were directly associated with arterial thrombosis. IPSET-thrombosis appears to be better than the traditional classification at identifying lower risk patients who do not need specific therapy.
Resumo Introdução: em pacientes com trombocitemia essencial (TE), complicações vasculares contribuem para morbidade e mortalidade. Para melhor predizer a ocorrência de eventos trombóticos, um escore prognóstico internacional de trombose para TE (IPSET-trombose) foi recentemente desenvolvido. Apresentamos aqui a aplicação desse escore e comparamos seus resultados com o sistema de classificação usual. Método: avaliamos retrospectivamente as características e os fatores de risco para trombose em 46 pacientes com diagnóstico de TE que foram atendidos nos últimos 6 anos na Faculdade de Medicina do ABC. Resultados: trombose em território arterial é mais prevalente que em sítio venoso. Observamos que fatores de risco cardiovascular (hipertensão, hipercolesterolemia, diabetes mellitus e tabagismo) foram considerados fatores de risco para trombose (p<0,001). Idade > 60 anos e presença de mutação JAK2 V617F não se associaram à ocorrência de eventos trombóticos. Nenhum paciente classificado como baixo risco pelo IPSET-trombose apresentou evento trombótico. Quando comparado à classificação de risco tradicional, IPSET-trombose foi capaz de identificar dois pacientes que evoluíram com trombose no seguimento e estavam categorizados no grupo de baixo risco. Leucocitose ao diagnóstico foi mais prevalente em pacientes que apresentaram trombose arterial (p=0,02), e esplenomegalia, entre aqueles com evento trombótico venoso (p=0,01). Conclusão: fatores de risco cardiovascular e leucocitose se associaram de forma direta com trombose arterial. IPSET-trombose parece ser melhor que a classificação tradicional na identificação de pacientes de baixo risco que não precisam de terapia específica.
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Humanos , Masculino , Feminino , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Trombose/etiologia , Medição de Risco/métodos , Trombocitemia Essencial/complicações , Prognóstico , Valores de Referência , Trombose/diagnóstico , Brasil , Fumar/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Complicações do Diabetes , Janus Quinase 2/genética , Hospitais Públicos/estatística & dados numéricos , Hipertensão/complicações , Pessoa de Meia-IdadeRESUMO
Myelodysplastic syndrome (MDS) cases comprise a heterogeneous group of hematological disorders that are characterized by impaired hematopoiesis, with cytopenias of different grades and risk of developing acute myeloid leukemia. MDS may rarely be associated with thrombocytosis. In such cases, myelodysplasia and myeloproliferative disorders may overlap, making correct diagnosis difficult. We herein describe a case of MDS with thrombocytosis, Janus kinase 2 gene mutation-positive and Perls' staining-negative, which was initially classified as essential thrombocythemia (ET). This case highlights that MDS may be misdiagnosed as ET and inappropriate treatment may be initiated. Therefore, it is crucial to carefully combine all available data on morphology and immunophenotyping, and to perform the necessary molecular, cytogenetic and molecular cytogenetic analyses, in order to correctly diagnose this disease.
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CONTEXT: Stroke following scorpion stings is rare. We report a fatal envenomation involving multiple, extensive brain infarcts in a patient with a previous diagnosis of essential thrombocythemia (ET) who was stung by Tityus serrulatus (T. serrulatus). CASE DETAILS: A 44-year-old woman with a diagnosis of low-risk ET (platelets <1,000,000/mm3, age <60 years and no history of thrombosis; positive JAK2V617F mutation) was admitted to a local ED 1 h after being stung by T. serrulatus on the left foot. She developed signs of severe envenomation, including several episodes of profuse vomiting, pallor and confusion soon after the sting, followed by shock (BP: 90/60 to 60/40 mmHg) and was treated with scorpion antivenom, vasopressors and mechanical ventilation. A brain computed tomography (CT) scan (54-h poststing) revealed diffuse bilateral cerebellar hypodensity, with partial involvement of both occipital lobes and thalamus, obstructive hydrocephaly with signs of cerebrospinal fluid extravasation, and ascending transtentorial herniation, suggestive of bilateral ischemia involving the posterior cerebral circulation. External ventricular drainage resulted in no improvement and brain death was confirmed on day 10. DISCUSSION: Several mechanisms have been proposed to explain stroke following scorpion stings, such as sympathetic stimulation, myocardial dysfunction, hypotension/shock, arrhythmias and coagulopathy. Ischemic stroke is one of the most serious complications of ET. The risk factors for thrombotic/ischemic events in patients with ET include age (≥60 years) and previous vascular events. Severe scorpion envenomation resulting in myocardial dysfunction and systemic inflammatory response syndrome may increase the overall risk of arterial thrombosis in this patient.