Efficacy and safety of peginterferon-α2b for treatment of myeloproliterative neoplasms / 南方医科大学学报

OBJECTIVE@#To evaluate the clinical efficacy and adverse reactions of peginterferon-α2b for treatment of chronic myeloproliferative neoplasms (MPN).@*METHODS@#We retrospectively analyzed the data of 107 patients with MPN, including 95 with essential thrombocythemia (ET) and 12 with polycythemia vera (PV), who all received peginterferon-α2b treatment for at least 12 months. The clnical and follow-up data of the patients were analyzed to evaluate the efficacy and adverse reactions of the treatment.@*RESULTS@#After receiving peginterferon- α2b treatment, both ET and PV patients achieved high hematological remission rates, and the total remission rates did not differ significantly between the two groups (86% vs 78%, P>0.05). In the overall patients, the spleen index decreased by 13.5% (95%CI: 8.5%-18.5%) after the treatment. The patients with hematological remission showed a significantly greater reduction of the total symptom score than those without hematological remission (P < 0.01). The median percentage of JAK2V617F allele load of PV patients decreased from 67.23% (49.6%-84.86%) at baseline to 19.7% (0.57%-74.6%) after the treatment, and that of JAK2V617F-positive ET patients decreased from 48.97% (0.45%-74.24%) at baseline to 22.1% (0.33%-65.42%) after the treatment. Mild adverse reactions (grade 1-2) were observed in both ET and PV groups without significant differences between them. The overall incidence of thrombotic events during the treatment was 2.8% in these patients, and no serious adverse reactions were observed.@*CONCLUSION@#For patients with chronic myelodysplasia, peginterferon-α2b treatment can achieve a high peripheral blood cell remission rate and maintain a long-term stable state with good effect in relieving symptoms such as splenomegaly. Peginterferon- α2b treatment caused only mild adverse reactions, which can be tolerated by most of the patients.

Trombocitemia esencial en pacientes adultos: 10 años de experiencia / Essential thrombocythemia in adul t patients: 10 years' experienc

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.

Influencia de la carga alélica del JAK2V617F en pacientes cubanos con trombocitemia esencial y mielofibrosis primaria / Influence of JAK2V617F allelic burden in Cuban patients with essential thrombocythemia and primary myelofibrosis

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)

Analysis of Differential Proteins Related to Platelet Activation in Patients with Essential Thrombocythemia Based on Label-Free Quantitative Technology / 中国实验血液学杂志

OBJECTIVE@#To analysis the specific protein markers of essential thrombocythemia (ET) based on proteomics technology, to explore and verify the differential protein related to platelet activation.@*METHODS@#Blood samples were obtained from ET patients and healthy people and a certain protein mass spectrometry was detected using label-free quantitative technology. The proteins relative abundance increased or down-regulated by 1.3 times in the disease group compared with the control group, and the protein abundance in the two groups t test P＜0.05 were defined as differential proteins. Bioinformatics analysis of the differential proteins was performed using GO and KEGG. The difference in the average protein abundance between the two groups was analyzed by t test and P＜0.05 was considered statistically significant. Differential proteins were selected for verification by parallel reaction monitoring (PRM) technology.@*RESULTS@#A total of 140 differential proteins were found, of which 72 were up-regulated and 68 were down-regulated. KEGG enrichment showed that the differential protein expression was related to the platelet activation pathway. The differential proteins related to platelet activation were GPV, COL1A2, GP1bα, COL1A1 and GPVI. Among them, the expressions of GPV, GP1bα and GPVI were up-regulated, and the expressions of COL1A2 and COL1A1 were down-regulated. PRM verification of COL1A1, GP1bα, GPVI and GPV was consistent with LFP proteomics testing.@*CONCLUSION@#Differential proteins in ET patients are related to platelet activation pathway activation.Differential proteins such as GPV, GPVI, COL1A1 and GP1bα can be used as new targets related to ET platelet activation.

IRF4 and IRF8 expression are associated with clinical phenotype and clinico-hematological response to hydroxyurea in essential thrombocythemia / 医学前沿

The morbidity and mortality of myeloproliferative neoplasms (MPNs) are primarily caused by arterial and venous complications, progression to myelofibrosis, and transformation to acute leukemia. However, identifying molecular-based biomarkers for risk stratification of patients with MPNs remains a challenge. We have previously shown that interferon regulatory factor-8 (IRF8) and IRF4 serve as tumor suppressors in myeloid cells. In this study, we evaluated the expression of IRF4 and IRF8 and the JAK2V617F mutant allele burden in patients with MPNs. Patients with decreased IRF4 expression were correlated with a more developed MPN phenotype in myelofibrosis (MF) and secondary AML (sAML) transformed from MPNs versus essential thrombocythemia (ET). Negative correlations between the JAK2V617F allele burden and the expression of IRF8 (P < 0.05) and IRF4 (P < 0.001) and between white blood cell (WBC) count and IRF4 expression (P < 0.05) were found in ET patients. IRF8 expression was negatively correlated with the JAK2V617F allele burden (P < 0.05) in polycythemia vera patients. Complete response (CR), partial response (PR), and no response (NR) were observed in 67.5%,10%, and 22.5% of ET patients treated with hydroxyurea (HU), respectively, in 12 months. At 3 months, patients in the CR group showed high IRF4 and IRF8 expression compared with patients in the PR and NR groups. In the 12-month therapy period, low IRF4 and IRF8 expression were independently associated with the unfavorable response to HU and high WBC count. Our data indicate that the expression of IRF4 and IRF8 was associated with the MPN phenotype, which may serve as biomarkers for the response to HU in ET.

Manejo anestésico de pacientes con trombocitemia esencial / Anesthetic management of a patient with essential trombocythemia

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)

Transformación cavernomatosa de vena porta asociada a trombocitemia esencial oculta

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.

Intracardiac thrombosis in essential thrombocythemia / Trombosis intracardiaca en trombocitemia esencial

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.

Successful Surgical Treatment of Left Ventricular Aneurysm with a Mobile Thrombus Concomitant with Essential Thrombocythemia / 日本心臓血管外科学会雑誌

Essential thrombocythemia is considered one of the chronic myeloproliferative disorders resulting in arterial thromboembolism, venous thrombosis, and bleeding tendency. We report a case of left ventricular aneurysm with successful treatment of the complications of this disease. A 66-year-old man who suddenly experienced right upper limb paralysis was carried to a nearby hospital. Computed tomography revealed multiple cerebral infarctions. An electrocardiogram confirmed findings of old myocardial infarctions in the anteroseptal wall. Echocardiography indicated a left ventricular aneurysm with mobile thrombus. The blood tests showed an abnormally high platelet count of 120×104/μl. His left ventricular thrombus showed an increasing tendency regardless of heparin administration ; thus, he was transferred to our hospital. The resection of the aneurysm and left ventricular restoration was performed emergently to avoid re-embolism. There was a soft thrombus inside the aneurysm at its apex. During cardiopulmonary bypass, the activated clotting time was not prolonged easily. We gave additional heparin and antithrombin III. The patient had no problem with hemostasis or postoperative bleeding. We started low-molecular-weight heparin from the second postoperative day and he was diagnosed with essential thrombocythemia by bone marrow biopsy. We started warfarin and aspirin on the fifth day after surgery. The number of platelets increased to 183×104/μl on the 8th day ; thus, oral administration of hydroxycarbamide was started. His platelet count fell to less than 100×104/μl around 3 weeks after surgery and he was discharged on the 34th day without new embolisms.

Vitamin D Deficiency and Janus kinase 2 V617F Mutation Status in Essential Thrombocythemia and Polycythemia Vera

@#Introduction: Vitamin D, which is known for its effects on calcium and bone metabolism, has recently been associated with haematological malignancies. We aimed to investigate the relationship between disease findings and vitamin D deficiency in essential thrombocythemia (ET) and polycythemia vera (PV). Material and Methods: This retrospective cohort study conducted in Turkey included 73 patients diagnosed with PV or ET according to WHO criteria between 2012 and 2018. Vitamin D deficiency was defined as 25-OH vitamin D < 20 ng/mL. Polymerase chain reaction (PCR) was used to detect the Janus kinase 2 (JAK2) V617F mutation. Results: Vitamin D deficiency was found in 66.7% of PV and 74.2% of ET patients. The median follow-up time of ET and PV patients was 48 months and 47 months, respectively. Patients with the JAK2 mutation had a higher prevalence of a history of thrombosis and age older than 65 years. There was a significant relationship between JAK2 positivity and vitamin D deficiency. Conclusion: There was a remarkably higher prevalence of vitamin D deficiency in JAK2 mutation-positive ET and PV patients. These patients should be carefully evaluated for vitamin D deficiency. More studies are required to further investigate the association between JAK2 and vitamin D.

Calidad de vida en pacientes con neoplasias mieloproliferativas crónicas Filadélfia negativas / Quality of life in patients with Philadelphia negative chronic myeloproliferative neoplasms

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).

Risk factors for recurrent thrombosis in patients with polycythemia vera and essential thrombocythemia / 中华血液学杂志

Objective@#To analyze the clinical characteristics of recurrent thrombosis in patients with polycythemia vera (PV) and essential thrombocythemia (ET) to probe the risk factors for recurrent thrombosis in patients with ET and PV.@*Methods@#The clinical data of 104 ET and PV patients with thrombosis in Beijing Anzhen Hospital from February 2001 to November 2016 were retrospectively analyzed. Thrombosis reoccurred in 38 patients. Statistical analyses were performed by multivariate logistic regression for risk factors of recurrent thrombosis in ET and PV patients.@*Results@#Recurrent thrombosis occurred in 36.5% of patients with ET/PV, the total incidence rate in ET and PV patients was 9.8% patient-years, 12.3% patient-years and 5.7% patient-years in ET and PV respectively. There were a total of 56 re-thrombotic events, and 42.1% of events occurred within 1 year after the first thrombosis. The arterial re-thrombosis was 97.4% (most of acute coronary syndrome, ACS), and venous events was 2.6%. The most common cases of re-thrombosis were ACS in ET patients (18 cases, 64.3%), and cerebral infarction in PV patients (7 cases, 70.0%). The number of PV patients with 2 times or more re-thrombotic events was significantly higher than that of ET patients (9 cases, 90.0% vs 7 cases, 25.0%). The proportion of the patients with WBC>12.5×109/L or Hct>45%, and thrombosis history or splenomegaly and high risk thrombotic events were higher than those with a single thrombus (52.6% vs 31.8%; 50.0% vs 30.0%; 86.8% vs 13.6%; 84.2% vs 33.3%; 52.6% vs 15.2%; 94.7% vs 53.0%; P values were 0.036,0.046, <0.001, <0.001, <0.001 and <0.001, respectively). Logistic regression analysis showed that thrombosis history (OR=13.697, P=0.025), splenomegaly (OR=13.301, P=0.034) and high risk stratification of thrombotic events (OR=44.618, P=0.025) were independent risk factors for recurrent thrombotic events.@*Conclusions@#ET and PV patients had a higher risk of re-thrombosis. The incidence of re-thrombosis in ET was higher than in PV, ACS was more common cases of re-thrombotic events; but PV patients were more susceptible to multiple re-thromboses than ET ones, also with more cerebral infarction. Previous thrombus history, splenomegaly and high risk stratification of thrombotic events were independent risk predictors for re-thrombosis of ET and PV patients.

A Case of Mitral Valve Replacement Complicated with Essential Thrombocythemia Preoperatively Interrupting Hydroxycarbamide / 日本心臓血管外科学会雑誌

Essential thrombocythemia (ET) is a myeloproliferative neoplasm characterized by thrombocytosis and malfunction of platelets. Both thrombosis and bleeding due to thrombocytosis may occur. An 81-year-old female patient complicated with ET underwent mitral valve replacement using a bioprosthetic valve due to severe mitral regurgitation. She had been diagnosed and treated with the hydroxycarbamide for ET. The hydroxycarbamide had been interrupted 14 days before the surgery, to prevent infection and delayed wound healing. At hospitalization for surgery, her platelet count rose to 1,290,000/μl from 790,000/μl. Readministration of a half dose of the hydroxycarbamide lowered the platelets to her original level. During the operation, more heparin was necessary to control activated coagulation time for cardiopulmonary bypass. She was discharged unaffectedly on 25 POD.

Major Changes to the 2017 Revision of the World Health Organization Classification of Myeloproliferative Neoplasms / 대한내과학회지

The World Health Organization (WHO) Classification of Tumors of Haematopoietic and Lymphoid Tissues was recently published in a revised fourth edition. The categories of myeloproliferative neoplasms (MPNs) have not significantly changed since the 2008 fourth edition of the classification; however, newly discovered mutations including CALR and CSF3R and improved characterizations and standardizations of morphological features of some entities, particularly BCR-ABL1-negative MPNs, have impacted the diagnostic criteria of disease entities, increasing the reliability and reproducibility of diagnoses. The 2017 revised edition attempts to incorporate new clinical, prognostic, morphologic, and genetic data that have emerged since the last edition. This article reviews the major changes in the classification and their rationale for MPN classification within the revised 2017 WHO system.

GATA1 Expression in BCR/ABL1-negative Myeloproliferative Neoplasms

BACKGROUND: This study aimed to determine GATA1 expression levels to better characterize subgroups in BCR/ABL1-negative myeloproliferative neoplasms (MPNs). METHODS: This study enrolled 49 patients diagnosed as having BCR/ABL1-negative MPN on the basis of the 2016 World Health Organization classification : nine polycythemia vera (PV), 17 essential thrombocythemia (ET), 12 prefibrotic primary myelofibrosis (prePMF), and 11 overt primary myelofibrosis (PMF). Relevant clinical and laboratory data were retrieved from the medical records. The molecular analysis of CALR and MPL mutations and quantification of JAK2 V617F allele burden were performed. GATA1 expression was assessed by an immunohistochemical assay on bone marrow biopsy. GATA1 expression was analyzed serially in 18 patients. RESULTS: GATA1 expression decreased significantly in PMF compared with that in other subtypes, while no statistical difference was identified between ET and prePMF. GATA1 expression did not differ according to the mutation profiles or the allele burden of JAK2 V617F, but it decreased significantly in patients with overt fibrosis or leukemic transformation. CONCLUSIONS: Our results suggest that GATA1 expression is significantly low in PMF and decreases with progressive fibrosis and possibly with leukemic transformation, although our attempt to accurately distinguish between subgroups using GATA1 immunohistochemical approach did not achieve statistical significance. A large patient cohort with long term follow-up is required to evaluate the prognostic value of GATA1 expression.

Analysis of follow-up results after percutaneous coronary intervention in patients with primary thrombocythemia / 中国介入心脏病学杂志

Objective To analyze the characteristics, treatment and prognosis during follow-up in patients with essential thrombocythemia(ET)after percutaneous coronary intervention(PCI). Methods A total of 9 patients with ET who had CAD and treated with PCI in our hospital from 2010-01 to 2017-07 were retrospectively studied. The basic clinical information with clinical data,data of coronary intervention,application of anti-platelet and platelet reducing drugs,and the results of long-term follow-up were recorded in all patients. Results There were 5 male and 4 female with a mean age of (60.9 ± 14.3) years The 9 patients included 3 cases of acute myocardial infaction(MI),3 cases of old MI,2 cases of unstable angina and 2 cases stable angina. Coronary angiography revealed that there were 4 cases with single vessle involved and 5 cases with two-three vessles involved. All the patients were implante with drug-eluting stents. The mean platelet counts of the patients at admission were(596±233)×109/L. In 4 patients, ET was diagnosed during current hospitalization and their mean platelet counts were(803±105)×109/L. All patients received dual anti-platelet drugs after PCI and 8 patients had hydroxyurea during follow-up. During the follow-up of (53.2±26.9) months,no cardiovascular events occurred. One case of gastrointestinal bleeding occurred during the follow-up due to gastric ulcer. Conclusions Application of platelet reducing therapy with dual anti-platelet drugs in ET patients after PCI is eff ective and safe.

Descripción de las caracteristicas clínicas de las neoplasias mieloproliferativas crónicas (NMPC). Primer informe del registro colombiano de NMPC / Description of the clinical characteristics of chronic myeloproliferative neoplasms (MPNs). First report of the colombian registry of MPNs

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.

Four Consecutive Recurrent Abortions in Patient with Essential Thrombocythemia

Essential thrombocythemia (ET) is characterized by most cases in which platelet counts exceed 1 million/µL. ET is usually no symptoms during non-pregnancy, but arterial and venous thrombosis and hemorrhage may develop in pregnancy. Pregnancy in these patients is associated with many complications in both pregnant women and fetuses such as recurrent abortion, intrauterine fetal growth restriction, preterm delivery, preeclampsia, and stillbirth. In these patients, aspirin, low-molecular-weight heparin (LMWH), and interferon alpha (INF-α) are recommended during pregnancy. We report a case of four consecutive abortions despite being treated with INF-α, low dose aspirin, and LMWH in patient with ET.

Application of prognostic score IPSET-thrombosis in patients with essential thrombocythemia of a Brazilian public service / Aplicação do escore prognóstico IPSET-trombose nos pacientes com trombocitemia essencial em um hospital público brasileiro

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.

Analysis of Essential Thrombocythemia Combining Myocardial Infarction in 10 Patients / 中国循环杂志

Objective: To analyze the characteristics, treatment and prognosis in patients with essential thrombocythemia (ET) combining myocardial infarction (MI). Methods: A total of 10 patients with ET combining MI treated in our hospital from 2003-01 to 2015-07 were retrospectively studied. The basic clinical information with major admission complaints, previous history and peripheral platelet counts were recorded;echocardiograph, coronary angiography (CAG), application of anti-platelet drugs and platelet reductive therapy with the prognosis were recorded in all patients. Results: There were 6 male and 4 female with a mean age of (55.3 ± 9.7) years, 7 patients with AMI and 3 with old MI. The platelet counts at admission were (500-599) × 109/L in 3 patients, (600-699) × 109/L in 1 patient, (700-799) × 109/L in 3 patients, (800-899) × 109/L in 1 patients, (900-999) × 109/L in 1 patient and more than 1000 × 109/L in 1 patient. Echocardiograph indicated that 5 patient had LVEF≤50%and 5 had LVEF>50%. CAG revealed that there were 9 cases with left anterior descending involved, 2 with circumlfex involved and 5 with right coronary involved. All patients received dual anti-platelet drugs before operation, 4 had hydroxyurea for (20-30) days before operation and no post-operative cardiovascular events occurred;6 patients without hydroxyurea medication and 1 of them was re-hospitalized for angina pectoris and 2 had progressed coronary lesions. Conclusion: Application of platelet reductive therapy at before and after interventional treatment may improve the prognosis in patients with ET combining MI.