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Journal of Applied Physiology... Dec 2015In the last few years, genetic and functional studies have provided important insight on the pathophysiology of excessive erythrocytosis (EE), the main sign of Chronic... (Review)
Review
In the last few years, genetic and functional studies have provided important insight on the pathophysiology of excessive erythrocytosis (EE), the main sign of Chronic Mountain Sickness (CMS). The recent finding of the association of the CMS phenotype with a single-nucleotide polymorphism (SNP) in the Sentrin-specific Protease 1 (SENP1) gene, and its differential expression pattern in Andean highlanders with and without CMS, has triggered large interest in high-altitude studies because of the potential role of its gene product in the control of erythropoiesis. The SENP1 gene encodes for a protease that regulates the function of hypoxia-relevant transcription factors such as Hypoxia-Inducible Factor (HIF) and GATA, and thus might have an erythropoietic regulatory role in CMS through the modulation of the expression of erythropoietin (Epo) or Epo receptors. The different physiological patterns in the Epo-EpoR system found among Andeans, even among highlanders with CMS, together with their different degrees of erythropoietic response, might indicate specific underlying genetic backgrounds, which in turn might reflect different levels of adaptation to lifelong high-altitude hypoxia. This minireview discusses recent genetic findings potentially underlying EE and CMS, and their possible physiological mechanisms in Andean highlanders.
Topics: Altitude; Altitude Sickness; Chronic Disease; Humans; Polycythemia; South America
PubMed: 26272318
DOI: 10.1152/japplphysiol.00271.2015 -
Osteoporosis International : a Journal... Apr 2016Increased fragility has been described in humans with polycythemia vera (PV). Herein, we describe an osteoporotic phenotype associated with decreased osteoblast activity...
UNLABELLED
Increased fragility has been described in humans with polycythemia vera (PV). Herein, we describe an osteoporotic phenotype associated with decreased osteoblast activity in a mouse model of PV and another mouse of polycythemia and elevated circulating erythropoietin (EPO). Our results are important for patients with PV or those treated with recombinant EPO (rEPO).
INTRODUCTION
PV and other myeloproliferative syndromes have been recently associated with an increased risk for fractures. However, the presence of osteoporosis in these patients has not been well documented. EPO, a hormone primarily known to stimulate erythropoiesis, has been shown recently to regulate bone homeostasis in mice. The aim of this study was to examine the bone phenotype of a mouse model of PV and compare it to that of animals with polycythemia caused by elevated circulating EPO.
METHODS
Bone mass and remodeling were evaluated by micro-computed tomography and histomorphometry. The JAK2(V617F) knock-in mouse, a model of human PV, manifests polycythemia and low circulating EPO levels. Results from this mouse were compared to wild type (wt) controls and the tg6 transgenic mouse that shows polycythemia caused by increased constitutive expression of EPO.
RESULTS
Compared to wt, both JAK2(V617F) and tg6 mice had a decrease in trabecular bone mass. Tg6 mice showed an additional modest decrease in cortical thickness and cortical bone volume per tissue volume (P < 0.01) suggesting a more severe bone phenotype than JAK2(V617F). Decreased osteoblast numbers and bone formation along with normal osteoclast numbers and activity were found in both mice.
CONCLUSIONS
This study indicates that PV is associated with low bone mass and decreased osteoblast activity in mice. Our results support future studies of osteoporosis in affected humans. Polycythemia caused by chronically elevated circulating EPO also results in bone loss, and implications on patients treated with rEPO should be evaluated.
Topics: Animals; Bone Density; Bone Diseases, Metabolic; Bone Remodeling; Disease Models, Animal; Erythropoietin; Male; Mice, Knockout; Mice, Transgenic; Osteoblasts; Osteogenesis; Polycythemia; Polycythemia Vera; X-Ray Microtomography
PubMed: 26650379
DOI: 10.1007/s00198-015-3412-7 -
Asian Journal of Surgery Mar 2023
Topics: Humans; Polycythemia; Hemangioblastoma; Kidney Neoplasms; Biomarkers, Tumor
PubMed: 36184290
DOI: 10.1016/j.asjsur.2022.09.070 -
European Journal of Haematology Jun 2023The management to reduce risk of thromboembolic complications in polycythemia vera and essential thrombocythemia are well established, but for other conditions with...
INTRODUCTION
The management to reduce risk of thromboembolic complications in polycythemia vera and essential thrombocythemia are well established, but for other conditions with elevated hemoglobin, hematocrit, or platelets there are no consensus regarding treatment and follow up.
AIMS
To assess frequency of elevated blood values in patients with thromboembolic event, how many of these should be investigated further regarding myeloproliferative neoplasm and if the risk of recurrent event is depending on underlying condition.
METHODS
Retrospective cohort study of 3931 adult patients in the county of Norrbotten, Sweden, with thromboembolism during 2017 and 2018.
RESULTS
Of the 3931 patients, 1195 had either elevated Hb, HCT, or platelets fulfilling the 2016 revised WHO criteria for PV and ET, and out of these 411 should be evaluated regarding underlying myeloproliferative neoplasms. Unexplained thrombocytosis and secondary erythrocytosis were associated with the highest rate of recurrent event as well as the most inferior restricted mean survival time.
CONCLUSION
Elevated blood values are common in patients with thromboembolic event and the high risk of recurrent event and inferior restricted mean survival time in patients with unexplained thrombocytosis and secondary erythrocytosis implicates the importance of finding and managing the underlying condition.
Topics: Adult; Humans; Polycythemia; Cohort Studies; Retrospective Studies; Thrombocytosis; Polycythemia Vera; Thromboembolism; Myeloproliferative Disorders
PubMed: 36725666
DOI: 10.1111/ejh.13938 -
The Journal of the Association of... Jan 2020
Observational Study
Topics: Humans; Polycythemia; Polycythemia Vera
PubMed: 31979931
DOI: No ID Found -
British Journal of Haematology Aug 2023Congenital erythrocytoses represent a heterogenous group of rare defects of erythropoiesis characterized by elevated erythrocyte mass. We performed molecular-genetic...
Congenital erythrocytoses represent a heterogenous group of rare defects of erythropoiesis characterized by elevated erythrocyte mass. We performed molecular-genetic analysis of 21 Czech patients with congenital erythrocytosis and assessed the mutual link between chronic erythrocyte overproduction and iron homoeostasis. Causative mutations in erythropoietin receptor (EPOR), hypoxia-inducible factor 2 alpha (HIF2A) or Von Hippel-Lindau (VHL) genes were detected in nine patients, including a novel p.A421Cfs*4 EPOR and a homozygous intronic c.340+770T>C VHL mutation. The association and possible cooperation of five identified missense germline EPOR or Janus kinase 2 (JAK2) variants with other genetic/non-genetic factors in erythrocytosis manifestation may involve variants of Piezo-type mechanosensitive ion channel component 1 (PIEZO1) or Ten-eleven translocation 2 (TET2), but this requires further research. In two families, hepcidin levels appeared to prevent or promote phenotypic expression of the disease. No major contribution of heterozygous haemochromatosis gene (HFE) mutations to the erythrocytic phenotype or hepcidin levels was observed in our cohort. VHL- and HIF2A-mutant erythrocytosis showed increased erythroferrone and suppressed hepcidin, whereas no overproduction of erythroferrone was detected in other patients regardless of molecular defect, age or therapy. Understanding the interplay between iron metabolism and erythropoiesis in different subgroups of congenital erythrocytosis may improve current treatment options.
Topics: Humans; Polycythemia; Hepcidins; Oxygen; Mutation; Receptors, Erythropoietin; Ion Channels
PubMed: 37246471
DOI: 10.1111/bjh.18891 -
Best Practice & Research. Clinical... Nov 2022Monochorionic (MC) twin pregnancies are at increased risk of neonatal morbidity and mortality due to the shared placenta with vascular connections that can give rise to... (Review)
Review
Monochorionic (MC) twin pregnancies are at increased risk of neonatal morbidity and mortality due to the shared placenta with vascular connections that can give rise to various complications, including twin-twin transfusion syndrome, twin anemia polycythemia sequence (TAPS), selective fetal growth restriction, and other hematological imbalances at birth. Each complication presents its own challenges and considerations in the neonatal period. Measurement of hemoglobin levels and reticulocyte count is required to establish a correct diagnosis. Placenta dye injection is needed to properly distinguish between the various conditions. Risk factors for adverse outcome in MC twins include prematurity, severe cerebral injury, and the type of MC pregnancy complication. We, therefore, recommend cerebral ultrasound examinations in all complicated MC twins at birth to rule out a severe brain injury. Lastly, we strongly encourage screening for hearing loss using automated auditory brainstem response in all spontaneous TAPS donors to prevent permanent speech development delay.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Fetofetal Transfusion; Polycythemia; Pregnancy, Twin; Placenta; Anemia; Twins, Monozygotic
PubMed: 35513960
DOI: 10.1016/j.bpobgyn.2022.03.016 -
LGBT Health Jan 2023The goal of this study was to evaluate contributing factors and management strategies for polycythemia in transmasculine patients on testosterone therapy. A...
The goal of this study was to evaluate contributing factors and management strategies for polycythemia in transmasculine patients on testosterone therapy. A retrospective analysis of medical records was performed for transmasculine patients on testosterone for at least 12 months. Data collected from each patient included age, body mass index (BMI), nicotine dependence, pulmonary disease status, obstructive sleep apnea (OSA) status, oophorectomy status, and testosterone route of administration. For patients who developed polycythemia, polycythemia management strategy data were collected. Five-hundred-eleven patients were evaluated and 113 (22%) experienced an episode of polycythemia. Within the polycythemia group, 77% of patients were younger than age 40, 56% had a BMI >30.0, 44% had current or former nicotine dependence, 12% had a pulmonary disease, 12% had OSA, and 47% had received an oophorectomy. The polycythemia group had a significantly higher average age, BMI, and dose of testosterone, and also had a higher proportion of patients with OSA and an oophorectomy. These results revealed that polycythemia is a common side effect for transmasculine patients on testosterone. Importantly, previous oophorectomy may be associated with polycythemia which appears to be a novel finding. This finding requires further research but provides the potential to be an important screening consideration for transmasculine patients after oophorectomy. Polycythemia will continue to be a major concern for patients on testosterone therapy, and this study provided important information for clinical practice and future research that will lead to improved outcomes.
Topics: Humans; Adult; Testosterone; Polycythemia; Retrospective Studies; Incidence; Tobacco Use Disorder; Transgender Persons; Sleep Apnea, Obstructive
PubMed: 35920834
DOI: 10.1089/lgbt.2022.0027 -
Hematology. American Society of... Dec 2019In the patient presenting with an elevated blood count who does not have an acquired clonal disorder causing a myeloproliferative neoplasm, hereditary erythrocytosis or... (Review)
Review
In the patient presenting with an elevated blood count who does not have an acquired clonal disorder causing a myeloproliferative neoplasm, hereditary erythrocytosis or hereditary thrombocytosis needs to be considered as a possible explanation. A young patient and/or those with a family history of myeloproliferative neoplasm should specifically raise this possibility. Among the causes of hereditary erythrocytosis are mutations in the genes in the oxygen sensing pathway and high-affinity hemoglobins. Hereditary thrombocytosis has been shown to be accounted for by mutations in THPO, MPL, and JAK2 genes. In those who have a possible hereditary erythrocytosis or thrombocytosis, the investigative pathway includes specific investigation to rule out the more common acquired clonal disorders, and, if indicated, other secondary causes, measurement of specific cytokines as indicated, and search for specific identified molecular lesions that have been shown to cause these hereditary disorders. There remain individuals who appear to have a hereditary disorder in whom a genetic lesion cannot currently be identified.
Topics: Adult; Genetic Diseases, Inborn; Humans; Janus Kinase 2; Male; Mutation; Polycythemia; Receptors, Thrombopoietin; Thrombocytosis
PubMed: 31808840
DOI: 10.1182/hematology.2019000047 -
Minerva Pediatrics Feb 2024Polycythemia is a disorder with several causes and risk factors. The clinical presentation is variable, ranging from asymptomatic newborns to cases with severe...
BACKGROUND
Polycythemia is a disorder with several causes and risk factors. The clinical presentation is variable, ranging from asymptomatic newborns to cases with severe physiological changes. The aim of this study was to assess the prevalence, risk factors and predictors of severity of polycythemia in a Portuguese level III Neonatal Intensive Care Unit (NICU).
METHODS
Case-control study of all term newborns with the diagnosis of polycythemia admitted to the NICU of the São João Universitary Hospital Center, Porto, Portugal, from January 1, 1999 to December 31, 2019; and who met one of the following inclusion criteria were eligible for the study: 1) Hct>65% or Hb>22 g/dL; and 2) Hb≥21 g/dL with clinical manifestations of polycythemia.
RESULTS
A total of 53 newborns fulfilled the inclusion criteria and were included in the study, corresponding to a prevalence of 0.57%. Birth outside the hospital was the only risk factor with statistical significance. Of 53 cases, 51 (96.23%) had symptomatic polycythemia. The most frequent symptoms were: hyperbilirubinemia (69.81%), hypoglycemia (52.83%), thrombocytopenia (50.94%), cardiorespiratory (33.96%), and neurological symptoms (33.96%). Of the 53 newborns evaluated, 41 (77.36%) needed treatment. The only risk factors that influenced the hematocrit value were maternal diabetes and fetal growth restriction.
CONCLUSIONS
The best way to improve the prognosis of polycythemia is to identify the risk factors present throughout pregnancy and make an early diagnosis and treatment. Out-of-hospital births should be avoided. The diagnosis should not be excluded, even if hemoglobin and hematocrit are within normal limits.
Topics: Pregnancy; Female; Humans; Infant, Newborn; Polycythemia; Case-Control Studies; Prevalence; Hematocrit; Infant, Newborn, Diseases; Hemoglobins; Risk Factors
PubMed: 38376233
DOI: 10.23736/S2724-5276.21.05851-1