Mountain sickness in altitude inhabitants of Latin America: A systematic review and meta-analysis.

OBJECTIVE: Chronic and acute mountain sickness is known worldwide, but most of the available information comes from the eastern continent (Himalayas) without taking into account the west which has the most recent group located at altitude, the Andes. The aim of this study was to synthesize the evidence on the prevalence of acute and chronic mountain sickness in Latin American countries (LATAM). METHODS: A systematic search of the variables of interest was performed until July 8, 2023 in the Web of Science, Scopus, PubMed and Embase databases. We included studies that assessed the prevalence of mountain sickness in high-altitude inhabitants (>1500 m.a.s.l) who lived in a place more than 12 months. These were analyzed by means of a meta-analysis of proportions. To assess sources of heterogeneity, subgroup analyses and sensitivity analyses were performed by including only studies with low risk of bias and excluding extreme values (0 or 10,000 ratio). PROSPERO (CRD42021286504). RESULTS: Thirty-nine cross-sectional studies (10,549 participants) met the inclusion criteria. We identified 5 334 and 2 945 events out of 10,000 with acute and chronic mountain sickness in LATAM countries. The most common physiological alteration was polycythemia (2,558 events), while cerebral edema was the less common (46 events). Clinical conditions were more prevalent at high altitudes for both types of MS. CONCLUSION: Acute mountain sickness (AMS) occurs approximately in 5 out of 10 people at high altitude, while chronic mountain sickness (CMS) occurs in 3 out of 10. The most frequent physiological alteration was polycythemia and the least frequent was cerebral edema.

Performance in the Six-Minute Walking Test Does Not Discriminate Excessive Erythrocytosis Patients in a Severe Hypoxic Environment.

BACKGROUND: Chronic exposure to severe hypoxia causes an increase in hematocrit (Hct) and hemoglobin concentration ([Hb]), which can lead to excessive erythrocytosis (EE) and impact physical performance. This work aims to determine the differences in the six-minute walking test (6MWT) between EE and healthy subjects residing at more than 5000 m. METHODS: A prospective, cross-sectional study was performed on 71 men (36 healthy and 25 suffering from EE) living in La Rinconada, Peru (5100 m). Basal levels of [Hb] and Hct were obtained. All the subjects performed the 6MWT, and distance reached, vital signs, dyspnea, and fatigue (Borg scale) at the end of the test were recorded. RESULTS: The average [Hb] and Hct levels in the control group were 18.7 ± 1.2 g/dL and 60.4 ± 7.1%, respectively, contrasting with EE subjects, who showed 23.4 ± 1.6 g/dL and 73.6 ± 5.9% (p < 0.001). However, no statistically significant differences were observed in BMI or other anthropometric parameters. At the end of the 6MWT, the distance traveled and vital constants were similar between both groups, except for arterial oxygen saturation, which was consistently lower in subjects with EE throughout the test. CONCLUSION: EE does not significantly affect 6MWT performance at high altitudes, nor the hemodynamic control during moderate aerobic exercise of subjects who live permanently in a severely hypoxic environment.

Updated threshold, renewed problems: should the diagnostic criteria of polycythemia vera be reconsidered? A retrospective cross-sectional cohort study.

OBJECTIVE: This aim of this study was to evaluate hemoglobin and hematocrit values of polycythemia vera and secondary polycythemia patients with updated World Health Organization thresholds. In addition, by determining our own threshold values, we aimed to demonstrate the necessity of bone marrow biopsy and genetic analysis to be used for further diagnosis in patients with high-normal hematocrit and hemoglobin values. METHODS: A cross-sectional and retrospective study was performed with the medical records of patients from Eskisehir City Hospital hematology clinics and outpatient clinics between July 1, 2019 and July 1, 2020. The study included patients with polycythemia, divided into two groups according to polycythemia vera and secondary polycythemia. A bone marrow biopsy was performed on patients with either Janus kinase mutation positivity and/or subnormal erythropoietin levels. Receiver operating characteristics analysis was used to find threshold values, and the diagnostic efficiency of these values in differentiating World Health Organization thresholds in 2008 and 2016 was evaluated. RESULTS: A total of 73 patients were included. The median age was 43.5 years (min: 18; max: 84). The hematocrit value of 54.1 was predicted to diagnose polycythemia vera with a sensitivity of 45% and a specificity of 80%. Subsequent analysis revealed that an hemoglobin value of 17.7 was indicative of diagnosing polycythemia vera with a sensitivity of 60% and a specificity of 63%. The mean follow-up length was 6.4 months (2-12). CONCLUSION: Our study demonstrated that modified World Health Organization criteria might lead to unnecessary additional tests for polycythemia vera patients with high-normal hemoglobin and hematocrit values.

Are coagulation profiles in Andean highlanders with excessive erythrocytosis favouring hypercoagulability?

Chronic mountain sickness is a maladaptive syndrome that affects individuals living permanently at high altitude and is characterized primarily by excessive erythrocytosis (EE). Recent results concerning the impact of EE in Andean highlanders on clotting and the possible promotion of hypercoagulability, which can lead to thrombosis, were contradictory. We assessed the coagulation profiles of Andeans highlanders with and without excessive erythrocytosis (EE+ and EE-). Blood samples were collected from 30 EE+ and 15 EE- in La Rinconada (Peru, 5100-5300 m a.s.l.), with special attention given to the sampling pre-analytical variables. Rotational thromboelastometry tests were performed at both native and normalized (40%) haematocrit using autologous platelet-poor plasma. Thrombin generation, dosages of clotting factors and inhibitors were measured in plasma samples. Data were compared between groups and with measurements performed at native haematocrit in 10 lowlanders (LL) at sea level. At native haematocrit, in all rotational thromboelastometry assays, EE+ exhibited hypocoagulable profiles (prolonged clotting time and weaker clot strength) compared with EE- and LL (all P < 0.01). At normalized haematocrit, clotting times were normalized in most individuals. Conversely, maximal clot firmness was normalized only in FIBTEM and not in EXTEM/INTEM assays, suggesting abnormal platelet activity. Thrombin generation, levels of plasma clotting factors and inhibitors, and standard coagulation assays were mostly normal in all groups. No highlanders reported a history of venous thromboembolism based on the dedicated survey. Collectively, these results indicate that EE+ do not present a hypercoagulable profile potentially favouring thrombosis.

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.

Treatment of Focal and Segmental Glomerulosclerosis Secondary to High Altitude Polycythemia with Acetazolamide.

Vizcarra-Vizcarra, Cristhian A., Eduardo Chávez-Velázquez, Carmen Asato-Higa, and Abdías Hurtado-Aréstegui. Treatment of focal and segmental glomerulosclerosis secondary to high altitude polycythemia with acetazolamide. High Alt Med Biol. 23:286-290, 2022.-Focal segmental glomerulosclerosis (FSGS) is a morphological pattern, caused by glomerular injury and is the leading cause of nephrotic syndrome in adults. We present the case of a 59-year-old female patient, resident of a high-altitude city (3,824 m), who had polycythemia and nephrotic syndrome. A renal biopsy was performed, and the findings were compatible with FSGS. The patient received phlebotomy 500 ml three times, which reduced, partially, the hemoglobin concentration. However, she had refractory proteinuria, despite the use of enalapril and spironolactone. We observed that proteinuria worsened with the increase in hemoglobin levels. So, she was treated with acetazolamide 250 mg bid for 4 months, which reduced proteinuria and hemoglobin. During the coronavirus disease 2019 (COVID-19) pandemic, the patient did not take acetazolamide and again, she had an increase in hemoglobin and proteinuria levels. We conclude that acetazolamide may be an effective treatment in FSGS due to high altitude polycythemia.

Hematological Reference Values According to Geographical Region in Jujuy, Argentina.

Armella, Flavia Noelia, and Sandra Stella Lazarte. Hematological reference values according to geographical region in Jujuy, Argentina. High Alt Med Biol. 23:232-239, 2022. Background: Hematological values vary with altitude above sea level. The purpose of this work was to determine the ranges of hematological reference, and the prevalence of anemia and erythrocytosis in adult blood donors from Jujuy, discriminated according to the geographical region, who assisted at the Centro Regional de Hemoterapia from 2016 to 2018. Materials and Methods: A cross-sectional retrospective study was carried out. Men and women donors belonging to the regions of Valles, Yungas, Quebrada, and Puna were analyzed. The percentiles 2.5 and 97.5 were obtained for the hemoglobin (Hb), hematocrit (Ht), red blood cell count (RBCC), and hematimetric indices, according to sex and region. Results: A total of 4,707 men and 3,326 women, ranging from 18 to 65 years of age, who met with the expected clinical criteria in donors, were studied. The anemia prevalence was 2.5% (95% confidence interval [CI] = 2.2%-2.8%), while the erythrocytosis was 4.9% (95% CI = 4.4%-5.4%). The RBCC, Hb, and Ht increased with altitude above sea level. Conclusions: The Hb and Ht were similar to those observed in the Andean populations living at similar altitudes. The anemia prevalence was lower than the global prevalence reported by the World Health Organization, while that of erythrocytosis increased with the altitude above the sea level. The evidence indicates the necessity for laboratories to obtain reference values for their target population. Registro Nacional de Investigaciones (Renis, Ministerio de Salud de Argentina) IS002323.

Potential limitations of diagnostic standard codes to distinguish polycythemia vera and secondary erythrocytosis.

Red cell overproduction is seen in polycythemia vera (PV), a bone marrow myeloproliferative neoplasm characterized by trilinear cell proliferation (WBC, platelets), as well as in secondary erythrocytosis (SE), a group of heterogeneous disorders characterized by elevated EPO gene transcription. We aimed to verify the concordance of the International Classification of Diseases (ICD) code-based diagnosis of "polycythemia" or "erythrocytosis" with the true clinical diagnosis of these conditions. We retrospectively reviewed the electronic medical records (January 1, 2005, to December 31, 2016) of adult patients with ICD codes of polycythemia and/or erythrocytosis who had testing done for the presence of the JAK2V617F mutation. We verified the accuracy of the ICD code-based diagnoses by meticulous chart review and established whether these patients fulfilled the criteria by the evaluating physician for PV or SE and according to the World Health Organization 2016 diagnostic guidelines. The reliability of ICD coding was calculated using Cohen's kappa. We identified and chart reviewed a total of 578 patient records. Remarkably, 11% of the patients had concurrent diagnosis codes for PV and SE and were unable to be classified appropriately without individual chart review. The ICD code-based diagnostic system led to misidentification in an important fraction of cases. This represents a problem for the detection of PV or SE cases by ICD-based registries and their derived studies. Research based exclusively on ICD codes could have a potential impact on patient care and public health, and limitations must be weighed when research findings are conveyed.

Primary erythrocytosis in a bitch - clinical and laboratorial aspects

Background: Primary erythrocytosis is a rare myeloproliferative disorder in dogs and cats characterized by an autonomous proliferation of erythroid precursors in the bone marrow, with low to normal serum erythropoietin concentration, resulting in elevated red blood cell count, hematocrit and hemoglobin concentration. Clinical signs are associated with increased blood volume and viscosity, and may include erythema, hyperemic mucous membranes and neurological signs such as seizures and ataxia. In veterinary medicine, the diagnosis should be made by exclusion of secondary or relative causes, after complementary exams. This report aims to describe a case of primary erythrocytosis in a bitch. Case: A 4-year-old mixed-breed bitch was referred to the Veterinary Medical Teaching Hospital from UFRGS with 3 convulsive episodes related by the owner. A previous abdominal ultrasonography revealed splenomegaly and the electrocardiogram showed no abnormalities. No alterations were observed at the physical examination. The laboratorial blood tests demonstrated a persistent erythrocytosis, with high hematocrit, hemoglobin and red blood cells count, thrombocytopenia and neutropenia, and total plasmatic protein within the reference interval. The bone marrow cytology revealed reduced cellularity, normal myeloid:erythroid ratio, erythroid hyperplasia, mild myeloid hyperplasia and moderate myelofibrosis. The serum erythropoietin measurement was within the reference range, and the blood gas analysis detected a slight decrease in partial oxygen pressure. Therefore, no evidence of secondary conditions was observed and the diagnosis of primary erythrocytosis could be made. Discussion: Since there is no definitive method, the diagnosis of primary erythrocytosis could be based on the exclusion of all secondary and relative causes of erythrocytosis. The absence of clinical signs of dehydration and high serum albumin levels were findings that conduced for the exclusion of the relative form of the disturbance. The echocardiography and the abdominal ultrasonography ruled out any cardiopulmonary condition or kidney neoplasm, the most common causes of absolute secondary erythrocytosis. The persistently high hematocrit levels and red blood cell counts are significant for the suspicion of primary erythrocytosis, although thrombocytopenia and neutropenia are not commonly reported. The clinical signs of seizure were correlated with increased blood viscosity and reduced blood flow at the central nervous system. The blood gas analysis discarded the occurrence of systemic hypoxia, and the normal levels of erythropoietin gives higher evidence of the occurrence of an autonomous proliferation of the erythroid precursors within the bone marrow. The bone marrow cytology confirmed erythroid hyperplasia and the reduced cellularity that could be attributed to myelofibrosis. Myelofibrosis was described in humans with polycythemia vera, but there are no reports in veterinary, and this occurrence must be elucidated. An identical mutation in the JAK2 gene was observed in humans with polycythemia vera and dogs with primary erythrocytosis, and occurs in more than 50% of humans with myelofibrosis. Further investigations are necessary for veterinary medicine. In conclusion, the systematic approach of all organic systems and the assessment of complementary exams are necessary for the diagnostic of primary erythrocytosis in dogs. This condition should be considered in the differential diagnosis of any erythrocytosis, considering the guarded prognosis of this hematologic disorder.

Familial erythrocytosis 2 and von Hippel-Lindau disease in the same pediatric patient.

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.

Prevalencia de policitemia neonatal y factores asociados en recién nacidos / Neonatal polycythemia prevalence and associated factors in newborns

Introducción: La policitemia afecta del 1 a 5% de los recién nacidos, se asocia a complica-ciones por afectación orgánica y sistémica en el neonato que puede ser prevenible. El ob-jetivo de la presente investigación fue determinar la prevalencia de Policitemia neonatal y sus factores asociados en recién nacidos en un servicio de maternidad Público de la ciudad de Cuenca-Ecuador. Métodos: Se realizó un estudio transversal, el universo estuvo conformado por todos los recién nacidos en el servicio de maternidad del Hospital ¨Vicente Corral Moscoso¨. La muestra fue probabilística de 470 neonatos y sus madres. Para identificar asociación se realizó mediante X2 y para medir intensidad de asociación se utilizó OR (IC 95%) y valor de P < 0.05. Resultados: Ingresaron al estudio en forma aleatoria 470 casos. Se obtuvo una prevalencia del 12.8%. La residencia materna del 93% fue por sobre los 2000 metros sobre el nivel del mar. Los factores asociados fueron: bajo peso al nacer (OR 3.8; IC95%: 1.9 ­ 7.5) P < 0.001), patología materna incluida la diabetes (OR 2.6, IC95%: 1.3 ­ 5.2) P = 0.013), toxemia del em-barazo (OR 2.3; IC95%: 0.7 ­ 7.6) P = 0.134 y asociación negativa con prematuridad (OR 0.3; IC 95%: 0.07 ­ 1.2) P = 0.099. Conclusiones: la prevalencia de policitemia neonatal es alta y se asocia significativamente con bajo peso al nacer, patología materna.

Introduction: Polycythemia affects 1 to 5% of newborns, it is associated with complications due to organic and systemic involvement in the newborn that can be preventable. The objective of this research was to determine the prevalence of neonatal polycythemia and its associated factors in newborns in a public maternity service in the city of Cuenca-Ecuador. Methods: A cross-sectional study was carried out, the universe was made up of all new-borns in the maternity service of the ¨Vicente Corral Moscoso¨ Hospital. The sample was probabilistic of 470 neonates and their mothers. To identify association, it was performed using X2 and to measure association intensity, OR (95% CI) and P value <0.05 were used. Results: 470 cases were randomly entered into the study. A prevalence of 12.8% was ob-tained. The 93% maternal residence was above 2000 meters above sea level. The associat-ed factors were: low birth weight (OR 3.8; 95% CI: 1.9 - 7.5) P <0.001), maternal pathology including diabetes (OR 2.6, 95% CI: 1.3 - 5.2) P = 0.013), pregnancy toxemia (OR 2.3; 95% CI: 0.7 - 7.6) P = 0.134 and negative association with prematurity (OR 0.3; 95% CI: 0.07 - 1.2) P = 0.099. Conclusions: the prevalence of neonatal polycythemia is high and is significantly associated with low birth weight, maternal pathology.

Global REACH 2018: dysfunctional extracellular microvesicles in Andean highlander males with excessive erythrocytosis.

High altitude-related excessive erythrocytosis (EE) is associated with increased cardiovascular risk. The experimental aim of this study was to determine the effects of microvesicles isolated from Andean highlanders with EE on endothelial cell inflammation, oxidative stress, apoptosis, and nitric oxide (NO) production. Twenty-six male residents of Cerro de Pasco, Peru (4,340 m), were studied: 12 highlanders without EE (age: 40 ± 4 yr; BMI: 26.4 ± 1.7; Hb: 17.4 ± 0.5 g/dL, Spo2: 86.9 ± 1.0%) and 14 highlanders with EE (43 ± 4 yr; 26.2 ± 0.9; 24.4 ± 0.4 g/dL; 79.7 ± 1.6%). Microvesicles were isolated, enumerated, and collected from plasma by flow cytometry. Human umbilical vein endothelial cells were cultured and treated with microvesicles from highlanders without and with EE. Microvesicles from highlanders with EE induced significantly higher release of interleukin (IL)-6 (89.8 ± 2.7 vs. 77.1 ± 1.9 pg/mL) and IL-8 (62.0 ± 2.7 vs. 53.3 ± 2.2 pg/mL) compared with microvesicles from healthy highlanders. Although intracellular expression of total NF-κB p65 (65.3 ± 6.0 vs. 74.9 ± 7.8.9 AU) was not significantly affected in cells treated with microvesicles from highlanders without versus with EE, microvesicles from highlanders with EE resulted in an ∼25% higher (P < 0.05) expression of p-NF-κB p65 (173.6 ± 14.3 vs. 132.8 ± 12.2 AU). Cell reactive oxygen species production was significantly higher (76.4.7 ± 5.4 vs. 56.7 ± 1.7% of control) and endothelial nitric oxide synthase (p-eNOS) activation (231.3 ± 15.5 vs. 286.6 ± 23.0 AU) and NO production (8.3 ± 0.6 vs. 10.7 ± 0.7 µM/L) were significantly lower in cells treated with microvesicles from highlanders with versus without EE. Cell apoptotic susceptibility was not significantly affected by EE-related microvesicles. Circulating microvesicles from Andean highlanders with EE increased endothelial cell inflammation and oxidative stress and reduced NO production.NEW & NOTEWORTHY In this study, we determined the effects of microvesicles isolated from Andean highlanders with excessive erythrocytosis (EE) on endothelial cell inflammation, oxidative stress, apoptosis, and NO production. Microvesicles from highlanders with EE induced a dysfunctional response from endothelial cells characterized by increased cytokine release and expression of active nuclear factor-κB and reduced nitric oxide production. Andean highlanders with EE exhibit dysfunctional circulating extracellular microvesicles that induce a proinflammatory, proatherogenic endothelial phenotype.

Global REACH 2018: Influence of excessive erythrocytosis on coagulation and fibrinolytic factors in Andean highlanders.

NEW FINDINGS: What is the central question of this study? Are coagulation and fibrinolytic factors disrupted in Andean highlanders with excessive erythrocytosis? What is the main finding and its importance? Excessive erythrocytosis is not associated with prothombotic disruptions in coagulation or the fibrinolytic system in Andean highlanders. Impairments in coagulation and fibrinolysis may not contribute to the increased vascular risk associated with excessive erythrocytosis. ABSTRACT: Increased coagulation and reduced fibrinolysis are central factors underlying thrombotic risk and events. High altitude-induced excessive erythrocytosis (EE) is prevalent in Andean highlanders, contributing to increased cardiovascular risk. Disruption in the coagulation-fibrinolytic axis resulting in uncontrolled fibrin deposition might underlie the increased thrombotic risk associated with high-altitude EE. The experimental aim of this study was to determine whether EE is associated with a prothrombotic blood coagulation and fibrinolytic profile in Andean highlanders. Plasma coagulation factors (von Willebrand factor and factors VII, VIII and X), fibrinolytic factors [tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1)] and D-dimer levels were determined in 26 male residents of Cerro de Pasco, Peru (4340 m a.s.l.): 12 without EE (age, 40 ± 13 years; haemoglobin, 17.4 ± 1.9 g/dl) and 14 with EE (age, 43 ± 15 years; haemoglobin, 24.4 ± 1.6 g/dl). There were no significant differences in von Willebrand factor (40.5 ± 24.8 vs. 45.5 ± 22.4%), factor VII (77.0 ± 14.5 vs. 72.5 ± 8.9%), factor VIII (55.6 ± 19.8 vs. 60.7 ± 26.8%) and factor X (73.9 ± 8.3 vs. 67.3 ± 10.9%) between the Andean highlanders without or with EE. The t-PA antigen (8.5 ± 3.6 vs. 9.6 ± 5.4 ng/ml), t-PA activity (5.5 ± 2.4 vs. 5.8 ± 1.6 IU/ml), PAI antigen (45.0 ± 33.8 vs. 40.5 ± 15.8 ng/ml), PAI-1 activity (0.24 ± 0.09 vs. 0.25 ± 0.11 IU/ml) and the molar concentration ratio of active t-PA to active PAI-1 (1:0.051 ± 0.034 vs. 1:0.046 ± 0.021 mmol/l) were also similar between the groups, as were D-dimer levels (235.0 ± 126.4 vs. 268.4 ± 173.7 ng/ml). Collectively, the results of the present study indicate that EE is not associated with a hypercoagulable, hypofibrinolytic state in Andean highlanders.

Eritrocitosis secundaria a cardiopatía congénita como causa de pseudohipercalemia / Secundary erithrocitosis from congenital heart disease as a cause of pseudohiperkalemia

Resumen El potasio es, sin lugar a duda, uno de los componentes más importantes del balance hidroelectrolítico, además de ser uno de los exámenes de laboratorio más solicitados en el ámbito clínico. La hipercalemia se define por un valor sérico mayor a 5.5 mEq/L y su principal diagnóstico diferencial es la pseudohipercalemia o hipercalemia espuria. Esta se define como elevación del potasio solo en componente sérico y no plasmático con una diferencia mínima de 0.5 mEq/L. Entre las causas de pseudohipercalemia se encuentran factores mecánicos, químicos, contaminantes, temperatura y tiempo de procesamiento de la muestra. Se reporta el caso de un paciente masculino de 22 años de edad, con antecedentes de cardiopatía cianosante, que cursa con elevación espuria de potasio en suero, con aumento aislado severo del hematocrito y trombocitopenia concomitante, que luego mostraría valores normales en plasma.

Abstract Potassium is, without a doubt, one of the most important components of hydroelectrolitic balance, as well as being one of the most requested laboratory exams in the clinical setting. Hyperkalemia is defined as serum value above 5.5 mEq/L, and its main differential diagnosis is pseudohyperkalemia or spurious hyperkalemia. This conditioned is defined as an elevation of potassium levels exclusively in serum and not in plasma, with a minimal difference of 0.5 mEq/L between these measurements. Some of the causes of pseudohyperkalemia include mechanical factors, chemicals, contaminants, temperature and the time of sample processing. It is reported the case of a 22-year-old male with history of cyanotic heart disease that presented with a spurious elevation of serum potassium, with a severe increment in hematocrit and concomitant thrombocytopenia, that would later show normal levels in plasma.

Diagnostic Performance of Erythropoietin Levels in Polycythemia Vera: Experience at a Comprehensive Cancer Center.

INTRODUCTION: Considering the evolving diagnostic criteria of polycythemia vera (PV), we analyzed the utility of serum erythropoietin (EPO) as a predictive marker for differentiating polycythemia vera (PV) from other etiologies of erythrocytosis. PATIENTS AND METHODS: We conducted a retrospective study after a review of electronical medical records from January 2005 to December 2016 with diagnosis of erythrocytosis using International Classification of Disease-specific codes. To evaluate the diagnostic performance of EPO levels and JAK2-V617F mutation, we constructed a receiver-operated characteristic curve of sensitivity versus 1-specificity for serum EPO levels and JAK2-V617F mutation as predictive markers for differentiating PV from other causes of erythrocytosis. RESULTS: We surveyed 577 patients with erythrocytosis. Median patient age was 59.2 years, 57.72% (n = 329) were male, 86.3% (n = 491) were white, and only 3.3% (n = 19) were African American. A total of 80.88% (n = 351) of those diagnosed with PV had a JAK2-V617F mutation compared to only 1.47% (n = 2) whose primary diagnosis was secondary polycythemia. When comparing JAK2-V617 mutation to the EPO level, the area under the curve of JAK2-V617 (0.8970) was statistically larger than that of EPO test (0.6765). Therefore, the PV diagnostic methodology using JAK2-V617 is better than the EPO test. An EPO level of < 2 mIU/mL was > 99% specific to predict PV but was only 12% sensitive. CONCLUSION: In the appropriate clinical setting, cytogenetic and molecular studies such as JAK2 mutation status prevail as the most useful tools for PV case identification. The use of isolated EPO to screen patients with erythrocytosis is not a good diagnostic approach.