Erythrocytosis after hematopoietic stem cell transplantation: report of 3 cases and literature review / 中华内科杂志

This is a report of three cases of three male patients. One of the patients had myelodysplastic syndrome, and two had aplastic anemia; their ages were 28, 32, and 21 years old, respectively. Two patients underwent sibling allogeneic hematopoietic stem cell transplantation, and one underwent haploidentical hematopoietic stem cell transplantation. All the patients showed elevated hemoglobin and hematocrit at 6, 16, and 9 months after transplantation, with normal white blood cells and platelets and no splenomegaly. All causes of secondary polycythemia were ruled out. Bone marrow morphology showed no erythroid hyperplasia. The PCR result for BCR-ABL (P210, P230, P190, and variants) was negative, and there were no mutations at the amino acid site 617 of JAK2, exon 12 of JAK2, exon 9 of CALR, and amino acid site 515 of MPL. All three patients had hypertension. One patient was treated with amlodipine, and the other two patients were treated with angiotensin receptor blockers. The durations of erythrocytosis for these three patients were 6 years and 3 months, 4 years and 7 months, and 5 years and 3 months, respectively through December 2022. There was no tendency for spontaneous remission. Erythrocytosis after hematopoietic stem cell transplantation is a rare complication. Previous reports in the literature suggest that the mechanism of post-transplant erythrocytosis in recipients of allogeneic hematopoietic stem cell transplantation may be different from that of recipients of other transplants.

Estratificacion de riesgo y pronostico de las eritrocitosis patologicas en la altura / Risk stratification and prognosis of pathological erythrocytoses at altitude

Introducción. Las eritrocitosis patológicas en la altura afectan al 10 % de la población constituyéndose una causa importante de morbilidad por enfermedades no transmisibles. Suscita emergente categorizar la severidad de estas eritrocitosis para estimar su evolución y tratamientos adecuados. Objetivo. Estratificar el riesgo de las eritrocitosis patológicas en la altura considerando parámetros de severidad que sean de utilidad clínica en el pronóstico y tratamiento. Material y métodos. Estudio transversal retrospectivo de 283 historias clínicas de pacientes con eritrocitosis patológica de altura (EPA) o eritrocitosis secundaria (ES), residentes en altura (>3600 m s. n. m) y diagnosticados entre gestiones 2000 a 2021. Se identificó características clínico-laboratoriales diferenciales respecto del diagnóstico, respuesta al tratamiento y evolución de pacientes. Se planteó 3 niveles de estratificación de riesgo (bajo, intermedio, alto) considerando variaciones en síntomas de hiperviscosidad, eritropoyetina, complicaciones y comorbilidades. Resultados. 194 pacientes correspondieron al grupo de riesgo bajo, 67 al riesgo intermedio y 22 al riesgo alto. Riesgo bajo conllevó Epo 30 mUI/ml (30-100 mUI/ml), tratamiento con atorvastatina-aspirina, respuestas parciales y pronóstico regular, concerniendo pacientes con ES asociada a patologías pulmonares leves. Riesgo alto reflejó Epo >100 mUI/ml, inclusión de hidroxiurea al tratamiento con atorvastatina, menor respuesta y pronóstico desfavorable, incumbiendo pacientes >60 años con ES asociada a patologías pulmonares crónicas severas o complicaciones por eritrocitosis. Conclusiones. Contar con niveles de riesgo para las eritrocitosis patológicas permite conjeturar su pronóstico y optimizar decisiones terapéuticas.

Introduction. Pathological erythrocytoses at altitude affect 10% of the population, representing an important cause of morbidity from non-communicable diseases. Categorizing the severity of such erythrocytoses to estimate their evolution and suitable treatments becomes emergent. Objective. To stratify the risk of the pathological erythrocytoses at high altitude considering severity parameters useful for prognosis and treatment. Material and methods. Retrospective cross-sectional study that included 283 medical records of patients with Chronic Mountain Sickness-erythrocytosis (CMS-e) or Secondary Erythrocytosis (SE), inhabitants at high altitude (>3600 m a. s. l.) diagnosed between 2000 to 2021. Differential clinical-laboratory characteristics regarding the diagnosis, response to treatment and evolution of patients were identified. Three risk groups (low, intermediate, high) were raised, considering variations about hyperviscosity symptoms, erythropoietin levels, complications, and comorbidities. Results. 194 patients corresponded to the low-risk group, 67 to the intermediaterisk and 22 to the high-risk. Low-risk group involved Epo 30 mIU/ml (30-100 mIU/ ml), treatment with atorvastatin-aspirin, partial responses and favorable prognosis, concerning patients with SE attributed to mild lung diseases. High-risk reflected Epo >100 mIU/ml, inclusion of hydroxyurea to the treatment with atorvastatin, poor response and unfavorable prognosis, involving patients >60 years of age with SE attributed to severe and chronic lung diseases or complications due to erythrocytosis. Conclusion. Counting on a risk stratification for pathological erythrocytosis at high altitude allows to assess the prognosis and optimize therapeutic decisions.

Variaciones fenotípicas relacionadas a respuestas hipóxicas entre andinos a distintas altitudes / Phenotypic variations related to hypoxic responses among Andeans at different altitudes

Introducción. La adaptación a grandes altitudes implica cambios evolutivos que conllevan respuestas adaptativas, como a la hipoxia. Los andinos desarrollaron fenotipos eritroides diferentes en relación con otras poblaciones a gran altitud que pueden variar dependiendo la altitud. Objetivo. Determinar las variaciones fenotípicas de hemoglobina (Hb), saturación de oxígeno (SpO2), P50 y lactato en andinos bolivianos con radicatorias entre 400, 4000 y 5000 msnm. Material y métodos. Estudio descriptivo transversal de tipo prospectivo. Se recolectó sangre venosa periférica de andinos bolivianos (n=124) nacidos a 4000 m, pero con radicatoria en altitudes diferentes (400 m, 4000 m, 5000 m), así como de aquellos con eritrocitosis patológicas. Adicionalmente, se recolectó muestras de europeos residentes a 4000 m (n=11). Se realizó estudios de hemograma, oximetría y gasometría. La P50 fue calculada con fórmula de Lichtman. Resultados. Los andinos sanos, comparados entre distintas altitudes, reflejaron aumento de Hb al ser mayor la altitud (p: 0,001), empero disminución de SpO2 (p: 0,001) y P50 (p: 0,001); sin variaciones en lactato. Los europeos a 4000 m, en relación con andinos a la misma altitud, presentaron Hb incrementada (p: 0,01), SpO2 y P50 sin variaciones, pero lactato significativamente aumentado (p: 0,001). Los pacientes con eritrocitosis comparados con sujetos sanos, a 4000 m y 5000 m respectivamente, presentaron Hb aumentada (p: 0,001); SpO2 disminuida (p: 0,001); P50 sin variaciones, pero lactato incrementado (p: 0,01). El lactato elevado en sujetos a 5000 m con eritrocitosis fue llamativo (1,7 mmol/L). Conclusiones. Las variaciones fenotípicas observadas entre andinos en diferentes altitudes constituyen una expresión de una adaptación parcial a la altura.

Introduction. Human adaptation to high altitude involves evolutionary changes leading adaptive responses, such as to hypoxia. Andeans developed different erythroid phenotypes in relation to other populations at high altitude, which can vary depending on the altitude. Objective. To determine the phenotypic variations of hemoglobin (Hb), oxygen saturation (SpO2), P50 and lactate in Bolivian Andeans residing between 400, 4000 or 5000 masl. Material and methods. Prospective cross-sectional descriptive study. Peripheral venous blood from Bolivian Andeans (n=124) born at 4000 m, but residing at different altitudes (400 m, 4000 m, 5000 m), likewise from those with pathological erythrocytosis were collected. Additionally, samples from Europeans residing at 4000 m (n=11) were collected. CBC, oximetry and blood gas studies were performed. P50 was calculated using the Lichtman formula. Results. Healthy Andeans, compared between different altitudes, reflected an increased Hb (p: 0.001), but a decreased SpO2 (p: 0.001) and P50 (p: 0.001) as the altitude was higher; without variations in lactate. Europeans at 4000 m, related to Andeans at the same altitude, presented increased Hb (p: 0.01), SpO2 and P50 without variations, but significantly increased lactate (p: 0.001). Patients with erythrocytosis compared to healthy subjects, at 4000 m and 5000 m respectively, depicted increased Hb (p: 0.001); decreased SpO2 (p: 0.001); P50 without changes, but increased lactate (p: 0.01). Increased lactate in subjects with erythrocytosis at 5000 m was remarkable (1.7 mmol/L). Conclusion. The phenotypic variations observed among Andeans residing at different altitudes constitute an expression of partial adaptation to altitude.

Hipertensión arterial pulmonar y la eritrocitosis precede a la enfermedad pulmonar obstructiva crónica en fumadores residentes de grandes alturas / Pulmonary arterial hypertension and erythrocytosis precedes chronic obstructive pulmonary disease in smokers that live at high altitudes

Introducción:la eritrocitosis excesiva afecta a los habitantes de grandes alturas como La Paz, Bolivia, a 3600 msnm. El objetivo del pre-sente trabajo es determinar la existencia de hipertensión arterial pulmonar en pacientes fumadores con eritrocitosis excesiva, residentes de la gran altura entre 20 y 60 años de edad, casos estudiados en el Instituto Boliviano de Biología de Altura (IBBA) a lo largo de tres décadas.Materiales y métodos:estudio retrospectivo en el que revisamos sistemáticamente expedientes clínicos del IBBA. Se hallan 540 expedientes clínicos de la unidad de fisiología y fisiopatología respiratoria, de los cuales el 7% (30) fueron incluidos. Se buscaron correlaciones lineales entre edad, tabaquismo, hemoglobina sérica, altitud de residencia, presión arterial pulmonar y pruebas de fun-ción pulmonar. Resultados: existe correlación entre presión arterial pulmonar sistólica y hemoglobina sérica con R=0,579 (p=0,005). El índice de Tiffeneau (TIFF.O) tiene una correlación con la presión arterial media sistémica (PAM) (p=0,006). Conclusión: en pacientes con eritrocitosis excesiva fumadores residentes de grandes alturas, existe una correlación positiva entre presión arterial pulmonar sistólica y concentración de hemoglobina sin existir correlación con valores espirométricos que sugieran patrones obstructivos.

Introduction: Excessive erythrocytosis affects some people that live at high altitudes, such as in La Paz ­ Bolivia, 3600 meters above sea level. The objective of this paper is to determine the presence of pulmonary arterial hypertension in smokers that were diagnosed with excessive erythrocytosis. These smokers live at high altitudes. The Bolivian Institute of Altitude Biology (IBBA ­ Instituto Boliviano de Bio-logía de Altura) has studied this population for three decades. Materials and methods: Retrospective study in which we systematically reviewed IBBA's clinical records. We found 540 clinical records from the respiratory physiology and pathophysiology unit, from which we included 30 (7%). We also sought correlations between serum hemoglobin, pulmonary arterial pressure, and respiratory function tests. Results: we found that the correlation between systolic pulmonary artery pressure and serum hemoglobin is R = 0.579 (p = 0.005). We also found a strong correlation between the Tiffeneau index (TIFF.O) and the mean systemic arterial pressure (p = 0.005). Conclusion: in smokers diagnosed with excessive erythrocytosis that live at high altitudes, there is a correlation between systolic pulmonary arterial pressure and hemoglobin concentration, without any of them correlating with spirometry values that suggest an obstructive pattern.

Eritrocitosis patológicas con niveles de eritropoyetina baja e incrementada: características clínicas y laboratoriales / Pathological erythrocytosis with low and increased erythropoietin levels: clinical and laboratory characteristics

RESUMEN: Introducción: Los pacientes con eritrocitosis patológicas en la altura, Eritrocitosis Secundaria o Eritrocitosis Patológica de Altura, ocasionalmente suelen presentar niveles de eritropoyetina (EPO) con variaciones notables respecto de los parámetros normales, reflejando ya sea concentraciones muy bajas o muy altas de EPO. Objetivo: Analizar la prevalencia de las eritrocitosis con EPO disminuida y de las eritrocitosis con EPO incrementada, así como, las características laboratoriales y clínicas inmiscuidas entre ellas. Material y Métodos: Se realizó un estudio descriptivo transversal de tipo retrospectivo. Se analizó historias clínicas de 44 pacientes eritrocíticos; de estos, 22 pacientes (5 mujeres, 17 varones) con registros de EPO sérica disminuida (100 mUI/ml) que constituyeron el Grupo 2. Todos ellos residentes a una altura >3650 m s. n. m. Se recolectó datos demográficos, clínicos y laboratoriales; asimismo, datos referentes a los tratamientos administrados, seguimiento y respectivas respuestas en ambos grupos. Resultados: La frecuencia de las eritrocitosis patológicas con EPO disminuida representó 5 % y de aquellas con EPO elevada 5 %.: Se debe considerar estudios específicos en pacientes eritrocíticos con EPO baja para descartar Policitemia Vera, asimismo, los pacientes con EPO incrementada implican mayor complejidad en el manejo médico.

ABSTRACT: Introduction: Patients with pathological erythrocytosis at high altitude, Secondary Erythrocytosis or High Altitude Pathological Erythrocytosis, occasionally present notable variations of erythropoietin (EPO) levels regarding normal parameters, reflecting either very low or very high EPO concentrations. Objective: To analyze the prevalence of erythrocytosis with decreased EPO and erythrocytosis with increased EPO, as well as the laboratory and clinical characteristics involved between them. Material and methods: A retrospective cross-sectional descriptive study was conducted. Clinical records of 44 patients with erythrocytosis were analyzed; of these, 22 (5 women, 17 men) with records of decreased serum EPO (100 mIU/ml) ml) specified as Group 2. All of them were high altitude dwellers (>3650 m a. s. l). Demographic, clinical and laboratory data were collected, including data about administered treatments, follow-up and responses in both groups. Results: Frequency of pathological erythrocytosis with decreased EPO was 5% and with elevated EPO 5%. There were no representative differences between both groups concerning the CBC variables. Patients with increased EPO showed more complications of erythrocytosis (27%) compared to those with decreased EPO (0%). Two types of treatment regimen were evidenced in each group: a) ATV+ASA, and b) ATV+ASA+HU. Erythrocytosis patients with decreased EPO receiving ATV+ASA had higher favorable responses 90% versus those with elevated EPO (80%). The ATV+ASA+HU regimen reflected better applicability in the increased EPO group. Conclusion: Specific studies should be considered in erythrocytosis patients with decreased EPO to rule out Polycythemia Vera, similarly, patients with increased EPO imply more complexity at medical management.

Familial erythrocytosis 2 and von Hippel-Lindau disease in the same pediatric patient / Eritrocitosis familiar 2 y enfermedad de von Hippel-Lindau en el mismo paciente

Abstract Background: Patients with familial erythrocytosis type 2 have no increased risk of von Hippel-Lindau-associated tumors, although mutations in the VHL gene cause both pathologies. Case report: We present a case of a compound heterozygote patient with von Hippel-Lindau disease and familial erythrocytosis type 2. One of the mutations found in our patient, c.416C>G (p.Ser139Cys) of the VHL gene, has not been previously reported. This case is the second one reported where von Hippel-Lindau disease and familial erythrocytosis type 2 coexist in the same individual. Conclusions: Despite the low frequency of familial erythrocytosis type 2 in patients with von Hippel-Lindau disease, the possibility of this diagnosis should be considered to avoid unnecessary invasive studies to explain the polyglobulia in these patients and guarantee an adequate follow-up and vigilance of both diseases.

Resumen Introducción: Los pacientes con eritrocitosis familiar tipo 2 no muestran un riesgo incrementado de desarrollar tumores asociados con la enfermedad de von Hippel-Lindau, a pesar de que ambas afecciones están causadas por variantes patogénicas en el gen VHL. Caso clínico: Se presenta el caso de un paciente heterocigoto compuesto con enfermedad de von Hippel-Lindau y eritrocitosis familiar tipo 2. Una de las variantes patogénicas en el paciente, VHL c.416C>G (p.Ser139Cys), no ha sido previamente reportada. Este es el segundo reporte de caso en que la enfermedad de von Hippel-Lindau y la eritrocitosis familiar tipo 2 coexisten en el mismo individuo. Conclusiones: A pesar de la baja frecuencia de la eritrocitosis familiar tipo 2 en pacientes con enfermedad de von Hippel-Lindau, la posibilidad del diagnóstico debe considerarse con el fin de evitar estudios invasivos innecesarios para explicar la presencia de poliglobulia en estos pacientes y para garantizar un adecuado seguimiento y una correcta vigilancia de ambas enfermedades.

Arritmias cardíacas en habitantes de gran altura con diagnóstico de corazón pulmonar crónico / Cardiac arrhythmias in highlanders with a diagnosis of chronic cor pulmonale

Resumen Antecedentes: El corazón pulmonar crónico (CPC) muestra un incremento en habitantes que viven en grandes altitudes. Objetivo: Investigar la frecuencia de arritmias cardíacas y factores de riesgo para su desarrollo. Métodos: Estudio descriptivo y transversal; se revisó el registro de pacientes internados del Departamento de Cardiología del Instituto Nacional de Tórax, La Paz, Bolivia, entre enero de 2017 y junio de 2018; se incorporó a todos los individuos con diagnóstico de CPC, definido por criterios clínicos, electrocardiográficos y ecocardiográficos; se incluyó a 162 pacientes que cumplieron los criterios en el análisis; se utilizaron la t de Student y ANOVA. Resultados: Arritmias: fibrilación auricular (FA), 125 (75%); aleteo auricular (AA), 17 (10.5%); taquicardia auricular (TA), 17 (10.5%); extrasístoles, 3 (1.9%). Según el análisis univariado, los factores relacionados con el desarrollo de arritmias fueron: eritrocitosis: FA, RR: 1.33, otras arritmias (RR: 1.67), p = 0.0001; hipertensión arterial pulmonar: FA, RR: 3.10, otras arritmias (RR: 3.21), p = 0.0001; dilatación de aurícula derecha (AD): FA, RR: 1.92, otras arritmias (RR: 2.13), p = 0.0001; obesidad: FA, RR: 3.47, p = 0.001, otras arritmias (RR: 3.70), p = 0.001; hipertensión arterial sistémica: FA, RR: 3.10, p = 0.001, otras arritmias (RR: 3.21), p = 0.001. Según el análisis multivariado: eritrocitosis (RR: 2.2), dilatación de AD (RR: 1.2), p = 0.0001. Conclusiones: Se encontró FA con mayor frecuencia en los pacientes con CPC; los factores de riesgo con mayor significancia estadística para su presentación fueron la eritrocitosis y la dilatación de la AD.

Abstract Background: Chronic cor pulmonale (CPC), with increased presentation in high-altitude inhabitants. Objectives: Investigating the frequency of cardiac arrhythmias, and risk factors for its development. Methods: Descriptive, cross-sectional study, the inpatient registry of the Department of Cardiology of the National Institute of Torax, La Paz-Bolivia, from January 2017 to June 2018 was reviewed, all were incorporated with the diagnosis of CPC, defined by clinical criteria, electrocardiographic and echocardiographic, 162 patients who met the criteria were taken, the student's t-test and ANOVA were used for the analysis. Results: Arrhythmias: atrial fibrillation (AF) 125 (75%), atrial flutter (AA) 17 (10.5%), atrial tachycardia (AT) 17 (10.5%), extrasystoles 3 (1.9%). Univariate analysis of factors related to the development of arrhythmias: erythrocytosis: FA, RR: 1.33, other arrhythmias RR: 1.67, p = 0.0001, pulmonary arterial hypertension: FA, RR: 3.10, other arrhythmias RR: 3.21, p = 0.0001, right atrial dilation (AD): FA, RR: 1.92, other arrhythmias RR: 2.13, p = 0.0001, obesity: FA, RR: 3.47, p = 0.001, other arrhythmias RR: 3.70, p = 0.001, systemic arterial hypertension: FA: RR: 3.10, p = 0.001, other arrhythmias RR: 3.21, p = 0.001. Multivariate analysis: erythrocytosis (RR: 2.2), AD dilation (RR: 1.2), p = 0.0001. Conclusions: AF was found more frequently in patients with CPC, the risk factors with the greatest statistical significance for presentation were: erythrocytosis and AD dilation.

Rare Cases of Haemoglobin Variant Presented with Isolated Erythrocytosis

@#Haemoglobinopathies presenting with erythrocytosis is relatively rare. The clinicians might mistakenly diagnose such patients with other causes of erythrocytosis such as myeloproliferative neoplasm, etc instead of haemoglobinopathies. Here, we described two cases of haemoglobin variant, namely Haemoglobin Johnstown (Hb Johnstown) and Haemoglobin Bethesda (Hb Besthesda) that were detected following various futile investigations for persistent erythrocytosis. For both cases, the two main screening methods used were capillary electrophoresis (CE) and high performance liquid chromatography (HPLC). Approximately 30% of the high affinity haemoglobin (Hb) are not detected by electrophoresis method, however, in some cases, a variant Hb peak can be seen in chromatography method. Thus, a high index of suspicion of such diagnosis is utmost important as to not to miss the definitive diagnostic test by DNA analysis.

Fisiopatología de la anemia durante el embarazo: ¿anemia o hemodilución?

Iron is essential for health; its deficiency and excess are harmful. Our bodies have a high capacity to store and reuse iron so that its requirement is small (1-2 mg absorbed/day). Hepcidin, a hormone produced in the liver, has an important role in this elements homeostasis by blocking its transport protein, inhibiting its absorption in the duodenum and its release from the iron stores. During pregnancy, there is a new iron requirement for the placenta and fetus. This causes an increase in erythropoiesis; however, hemoglobin concentration decreases due to the greater vascular expansion. This results in hemodilution, which is evident starting the second trimester and returns to pre-gestational values at the end of the third trimester. Maternal iron deficiency anemia becomes a public health problem when it is moderate (7-14,5 g/dL) during pregnancy adversely affect the mother and neonate. For this reason, it is important to confirm if a pregnant woman with low hemoglobin levels is anemic or if it is due to hemodilution, a physiological process during pregnancy that does not require treatment. This review presents evidence to distinguish anemia from physiological hemodilution.

El hierro es un micronutriente fundamental para la salud; su deficiencia o su exceso son dañinos. Por ello, el organismo regula el requerimiento de hierro en base a su alta capacidad para almacenar y reciclar el hierro corporal de tal manera que su requerimiento es mínimo (1 a 2 mg absorbido/día). Esto se regula a través de la hepcidina, una hormona hepática que inhibe a la proteína transportadora de hierro (ferroportina) y con ello disminuye la absorción de hierro, o su liberación en los tejidos donde se almacenan. Durante la gestación hay una mayor necesidad de hierro para la placenta y el feto, y ello se evidencia en un aumento de la eritropoyesis; sin embargo, la concentración de la hemoglobina disminuye por efecto de una mayor expansión vascular. Esto determina una hemodilución que se evidencia a partir del segundo trimestre, y luego se va normalizando al final del tercer trimestre. La anemia materna por deficiencia de hierro se constituye en un problema de salud pública cuando es de magnitud moderada (7 a 14,5 g/dL) en la gestante afecta a la madre y al neonato. Por ello es importante determinar si una gestante con hemoglobina baja es realmente anémica o tiene una hemodilución, que es un proceso fisiológico que no requiere de tratamiento. Esta revisión presenta las evidencias para poder discriminar entre una anemia verdadera gestacional de una hemodilución fisiológica.

Hidronefrosis como causa de poliglobulia secundaria / Hydronephrosis as a cause of secondary polyglobulia

La policitemia primaria es producida por una mutación adquirida o heredada en las células progenitoras de los glóbulos rojos, mientras que la poliglobulia secundaria está relacionada con un aumento de la eritropoyetina sérica como respuesta a la hipoxia tisular o a la producción autónoma tumoral. Hace más de medio siglo que se conoce que la hidronefrosis puede actuar como una rara causa de eritrocitosis debido al aumento de producción de eritropoyetina por un riñón que censa una disminución de oxígeno, mecanismo también observado en la estenosis de la arteria renal y en los quistes renales. Se describe a continuación el caso de un paciente de 38 años con poliglobulia atendido en el Hospital Italiano de San Justo (Argentina), que presenta como hallazgo una hidronefrosis unilateral severa y cuya resolución quirúrgica a través de una nefrectomía revierte el cuadro hematológico de base. (AU)

Primary polycythemia is produced by an acquired or inherited mutation in progenitor cells of red blood cells, while secondary polyglobulia is related to an increase in serum erythropoietin in response to tissue hypoxia or autonomous tumor production. Since the middle of the twentieth century, the hydronephrosis is known to be a rare etiology of secondary polycythemia, with increased erythropoietin production caused by diminished oxygen sensing by the kidney, also seen in renal artery stenosis and kidney cysts. We describe a case of a 38 year old patient with polycythemia studied in the "Hospital Italiano de San Justo" (Argentina) that presented an incidental severe unilateral hydronephrosis, and nephrectomy was carried out as a final resolution of the hematological disorder. (AU)

Myeloproliferative Neoplasm in Newly Diagnosed Acute Ischemic Stroke Patients

OBJECTIVE: Myeloproliferative neoplasm (MPN) is considered as one of the risk factors of ischemic stroke. Some MPN patients manifest stroke as their first symptom. Our purpose was to assess diagnostic rate of MPN in newly diagnosed acute ischemic stroke patients. METHODS: This study was performed using National Health Insurance Service Ilsan Hospital dataset. Data retrieving was performed by defining by defining the patient with coding of acute ischemic stroke from January 2013 to June 2017. We selected only the patients who had checked brain magnetic resonance imaging and complete blood cell count (CBC) in emergency room or on admission. Among the results of CBC finding, hemoglobin and platelet count were analyzed. Erythrocytosis was defined >16.5 g/dL (male), >16 g/dL (female) according to revised World Health Organization (WHO) classification of polycythemia vera (PV) criteria. Thrombocytosis was >450,000/µL according to revised WHO classification of essential thrombocythemia (ET). RESULTS: Total number of newly diagnosed acute ischemic stroke was 1,613 patients. Seven patients (0.43%) were diagnosed MPN (ET=2, PV=5) after ischemic stroke. Patients who had thrombocytosis and erythrocytosis were 18 and 105, respectively. Three patients who had thrombocytosis were diagnosed MPN (ET=2, PV=1). Two patients with erythrocytosis were diagnosed MPN (PV=2). Two patients had both thrombocytosis and erythrocytosis, and two of them were diagnosed PV. Seventy-one patients who had erythrocytosis were normalized in follow-up period. Six patients who had thrombocytosis and 30 patients who had erythrocytosis did not further evaluate. CONCLUSION: CBC has to be carefully read and MPN can be suspected. Diagnosis must be confirmed by hematologist to initiate appropriate treatment. It is important to recognized suspected MPN patients to prevent stroke.

Diagnostic thought and progress of treatment of erythrocytosis in children / 中华实用儿科临床杂志

Erythrocytosis is characterized by an obvious increase in the erythrocyte count,the hematocrit and the hemoglobin content above reference range. Erythrocytosis is more common in adults,and is mostly polycythemia vera,but in children secondary erythrocytosis or congenital erythrocytosis caused by genetic mutations is more common. In recent years,the diagnosis and treatment of erythrocytosis have made new progress,now by the explanation of etiolo-gy,diagnosis and treatment progress of erythrocytosis,the aim of the thesis is to further enrich the knowledges of pe-diatricians about the diagnosis and treatment of erythrocytosis.

Application of simplified adjustment formula for coagulation test in individuals with erythrocytosis / 临床检验杂志

Objective To explore a simplified method of coagulation test for the individuals with erythrocytosis. Methods The antico-agulants, blood volume and fixed blood collecting volume were adjusted by the formula: anticoagulants (mL)＝(100－HCT×100)× blood (mL)×0.001 85. A total of 124 blood samples for coagulation testing in which the calcium ( Ca2+) interval was designated and hematocrit (HCT) was more than 55% were tested with calibrated anticoagulants, adjusted blood volume and fixed blood collection vol-ume [anticoagulant(mL)/0.055 5]. The results of plasma prothrombin time (PT), international standardization ratio (INR) and acti-vated partial thromboplastin time (APTT) before and after adjustment were compared. The results of the samples from 3 groups after adjustment were also compared. The relationship of HCT with unadjusted PT and APTT were simultaneously observed. Results The unadjusted results of PT, INR and APTT were significantly higher than those after anticoagulants adjustment (27.52±16.37 vs 12.49± 1.35, 2.31±1.47 vs 0.99±0.11 and 50.09±13.32 vs 33.37±5.05) with statistically significant difference in paired comparison (P＜0.05). No statistical difference was found in the comparison of the results for PT, INR and APTT after adjustment within the 3 groups ( PT: 12.49±1.35 vs 12.84±1.54 vs 12.82±1.76, INR:0.99±0.11 vs 1.02±0.13 vs 1.02±0.15, APTT: 33.37±5.05 vs 33.49±5.09 vs 32.83±5.06) (P＞0.05). HCT values of the patients were positively correlated with unadjusted PT (r＝0.461, P＜0.05) and APTT (r＝0.571, P＜0.05). Conclusion The coagulation test of the individuals with erythrocytosis may use to adjust the blood volume and the fixed blood collection volume provided calcium concentration in reference interval.

The prognostic impact of paraneoplastic erythrocytosis on patients with hepatocellular carcinoma after partial hepatectomy / 中华肝胆外科杂志

Objective To retrospectively study the prognostic impact of paraneoplastic erythrocytosis (PE) on patients with hepatocellular carcinoma (HCC) after liver resection.Methods 713 patients with HCC who underwent partial hepatic resection in The Affiliated Cancer Hospital of Guangxi Medical University were divided into two groups:the PE group (n =81) and the non-PE group (n =632).The overall survival between the two groups were compared after reducing confounding bias by using propensity score matching (PSM).Independent prognostic predictors were determined by the Cox proportional hazards model.Results 80 pairs of patients were matched using PSM.In the matched cohort,the PE group exhibited significantly longer overall survival (OS) compared to the NPE group of patients without erythrocytosis.The 1-,3-,and 5-year overall survival rates were 88.6％,74.2％,69.0％ in the PE group,and 91.0％,60.1％,41.6％ in the non-PE group,respectively (P ＜ 0.05).Using the log-rank test,tumor size ≥ 10cm,macrovascular invasion,Barcelona Clinic Liver Cancer (BCLC) stage C,PE and complete tumor encapsulation were significantly associated with OS in patients with HCC after liver resection.The Cox regression analysis indicated that tumor size ≥ 10 cm,and Barcelona Clinic Liver Cancer (BCLC) stage C were independent prognostic factors of poor prognosis,while complete tumor encapsulation and paraneoplastic erythrocytosis were independent predictors of good prognosis.Conclusions For patients with HCC who underwent surgical resection,patients with PE had better prognosis than those without PE under the condition of similar tumor burden.PE was an independent predictor of good prognosis.

Eritrocitose primária em cão: relato de caso / Primary erythrocytosis in dog: case report

A eritrocitose absoluta primária, também denominada de policitemia vera, é um distúrbio mieloproliferativo crônico de causa desconhecida, caracterizado pela proliferação clonal de células-tronco eritróides neoplásicas. Acomete cães de meia-idade entre seis e sete anos. As manifestações clínicas mais comuns são letargia, fraqueza, poliúria, polidipsia, sangramentos como epistaxe, hematúria, hematoemese, hematoquezia, até mesmo convulsões e ataxia. O diagnóstico é baseado em valores altos de hematócrito, geralmente acima de 70%, excluindo-se as causas de eritrocitose secundária. As concentrações séricas de eritropoietina estão normais ou diminuídas. O tratamento consiste em flebotomia e administração de hidroxiuréia. Relata-se o caso de uma cadela, raça Bichon Frise, 11 anos, que, no início do quadro, apresentou hematócrito de 84%, letargia, ataxia, mucosas congestas, cianose de língua, poliúria e polidipsia. Realizou-se o tratamento com hidroxiuréia durante oito anos, na dose de 15 a 30 mg/kg, a cada 24 horas, sem ocorrência de efeitos colaterais ou recidiva das manifestações clínicas.(AU)

Primary absolute erythrocytosis, also termed polycythemia vera, is a chronic myeloproliferative disorder of unknown cause. It is characterized by clonal proliferation of neoplastic erythroid stem cells. It affects middle-aged dogs between 6-7 years. The most common clinical manifestations are lethargy, weakness, polyuria, polydipsia, and bleeding such as epistaxis, hematuria, hematoemese, and hematochezia. Seizures and ataxia are also common. Diagnosis is based on high hematocrit values, generally above 70% excluding the causes of secondary erythrocytosis. Serum concentrations of erythropoietin are at a normal level or decreased level. Treatments consists of hydroxyurea and phlebotomy management. It is reported that case of female Bichon Frise, 11 years old who onset of the disease had a hematocrit of 84%, lethargy, ataxia, congested mucous membranes, tongue cyanosis, polyuria and polydipsia. The treatment with hydroxyurea was performed for 8 years, at a dose of 15 to 20mg/kg, every 24 hours, without occurrence of side effects or recurrence of clinical manifestations.(AU)

Hereditary polycythemia caused by mutation of ANK1 gene:a case report / 临床儿科杂志

Objective To explore the genetic characteristics, diagnosis, and treatment of hereditary spherical polycythemia (HS). Methods The clinical data of one case of HS was analyzed retrospectively, and related literatures were reviewed. Results The 5-year-old girl presented hemolytic anemia from 6 months old. Incubation of fragility tests was positive. Blood smears and red cell electron microscopy showed spherical red blood cells. DNA sequencing showed alterations in heterozygosity of stopgain SNV. The girl was diagnosed was HS, and was scheduled to undergo splenectomy at 6 years old. Conclusions HS is an autosomal dominant genetic disease, mainly manifested as anemia, hemolytic anemia, and splenomegaly. The early diagnosis depends on genetic testing.

Hb Heathrow β103(G5)Phe→Leu, a First Report in an Asian Patient with Erythrocytosis

Congenital erythrocytosis (CE) is a rare and heterogeneous disease. The high oxygen affinity hemoglobin (Hb) variants are the most common cause of CE. Herein, we report a Korean patient with isolated erythrocytosis. A 25-year-old man was referred to our hospital for evaluation of high Hb level (Hb 20.4 g/dL, hematocrit 58%, reticulocyte count 2.90%, white blood cell count 6.83×10⁹/L, and platelet count 195×10⁹/L). Bone marrow biopsy revealed normocellular marrow without myeloproliferative features. JAK2 (V617F, exon 12), CALR (exon 9), and MPL W515K/L mutations were not detected. P₅₀ (partial pressure at which Hb is half saturated with oxygen), which is an indicator of left-shift of oxygen dissociation curve (high oxygen affinity state), was 14.3 mm Hg (reference value 22.6–29.4 mm Hg). He was suspected to have CE. Mutation analysis of the HBB gene revealed the known Hb variant, Hb Heathrow [β103(G5)Phe→Leu]. This is the first report of Hb Heathrow in Asian.

Idiopathic erythrocytosis in a patient on chronic hemodialysis

A 78-year-old man on hemodialysis presented to our hospital with erythrocytosis. He had started hemodialysis 4 years previously, with a hemoglobin level of 9.8 g/dL, and was administered erythropoiesis stimulating agents and ferrous sulfate. Two years previously, his hemoglobin level increased to 14.5 g/dL and the treatment for anemia was discontinued. He continued hemodialysis thrice weekly; however, the hemoglobin level had increased to 17.0 g/dL at the time of presenting to our hospital. His serum erythropoietin level was 31.4 mIU/mL (range, 3.7-31.5 mIU/mL), carboxyhemoglobin level was 0.6% (range, 0-1.5%), and oxygen saturation in ambient air was 95.4%. The JAK2 V617F mutation was not observed and other bone marrow abnormalities were not identified. The patient was diagnosed with bladder cancer and a transurethral resection was performed. Eight months after the treatment of bladder cancer, his hemoglobin level was 15.1 g/dL, and he was diagnosed with idiopathic erythrocytosis.

Expression of GDF-15 in chronic mountain sickness rat model and discussion of the relationship with GDF-15 and hepcidin / 实用医学杂志

Objective To determine the growth differential factor 15 (GDF-15) in CMS rat model, investigate the significance of GDF-15 in CMS and the relationship between GDF-15 and hepcidin. Methods 32 rats of CMS model were taken as experimental group (EXP), the other 16 rats fed in Xining (CON) were taken as control group. The mRNA and protein expression levels of GDF-15 were detected respectively. Results Compared with that in CON group, the level of mRNA and protein of GDF-15 were significantly higher in EXP group (P<0.01). GDF-15 and EPO had correlation in EXP (r=0.397, P=0.031), but had no correlation with serum hepcidin in EXP (r = -0.224, P = 0.218). Conclusion GDF-15 can promote CMS and represent erythrocytosis, while GDF-15 has no inhibition to the expression of hepcidin.