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Journal of Internal Medicine Apr 2003
Topics: Adult; Blood Volume; Hematocrit; Humans; Male; Middle Aged; Plasma Volume; Polycythemia; Syndrome
PubMed: 12653867
DOI: 10.1046/j.1365-2796.2003.01105.x -
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 -
Genes Jul 2021Patients with idiopathic erythrocytosis are directed to targeted genetic testing including nine genes involved in oxygen sensing pathway in kidneys, erythropoietin... (Review)
Review
Patients with idiopathic erythrocytosis are directed to targeted genetic testing including nine genes involved in oxygen sensing pathway in kidneys, erythropoietin signal transduction in pre-erythrocytes and hemoglobin-oxygen affinity regulation in mature erythrocytes. However, in more than 60% of cases the genetic cause remains undiagnosed, suggesting that other genes and mechanisms must be involved in the disease development. This review aims to explore additional molecular mechanisms in recognized erythrocytosis pathways and propose new pathways associated with this rare hematological disorder. For this purpose, a comprehensive review of the literature was performed and different in silico tools were used. We identified genes involved in several mechanisms and molecular pathways, including mRNA transcriptional regulation, post-translational modifications, membrane transport, regulation of signal transduction, glucose metabolism and iron homeostasis, which have the potential to influence the main erythrocytosis-associated pathways. We provide valuable theoretical information for deeper insight into possible mechanisms of disease development. This information can be also helpful to improve the current diagnostic solutions for patients with idiopathic erythrocytosis.
Topics: Humans; Infant, Newborn; Infant, Newborn, Diseases; Polycythemia
PubMed: 34440324
DOI: 10.3390/genes12081150 -
Internal Medicine (Tokyo, Japan) Aug 2001Polycythemia is literally translated as "many cells in the blood". Only erythrocytosis (an alternative term for these disorders) produces polycythemia since leukocytes... (Review)
Review
Polycythemia is literally translated as "many cells in the blood". Only erythrocytosis (an alternative term for these disorders) produces polycythemia since leukocytes and platelets are present in blood in far smaller proportions. Polycythemia may be due to increased proliferation or decreased apoptosis of erythroid progenitors, or to delayed erythroid differentiation with an increased number of progenitor cell divisions. Prolonged red cell survival, another theoretical cause of polycythemia, has not yet been described and with intact regulatory mechanisms is unlikely to occur. Primary polycythemias result from abnormalities expressed in hematopoietic progenitors. In contrast, circulating factors cause secondary polycythemia (1). There are acquired and congenital causes of both primary and secondary polycythemia (1).
Topics: Angiotensin II; Erythropoiesis; Humans; Insulin-Like Growth Factor I; Polycythemia; Polycythemia Vera; Receptor, Angiotensin, Type 1; Receptors, Angiotensin; Receptors, Erythropoietin
PubMed: 11518102
DOI: 10.2169/internalmedicine.40.681 -
Blood Mar 1997Familial and congenital polycythemia, not due to high oxygen affinity hemoglobin or reduced 2,3-diphosphoglycerate in erythrocytes, is common in the Chuvash population...
Familial and congenital polycythemia, not due to high oxygen affinity hemoglobin or reduced 2,3-diphosphoglycerate in erythrocytes, is common in the Chuvash population of the Russian Federation. Hundreds of individuals appear to be affected in an autosomal recessive pattern. We studied six polycythemic Chuvash patients <20 years of age from unrelated families and 12 first-degree family members. Hemoglobins were markedly elevated in the index subjects (mean +/- standard deviation [SD] of 22.6 +/- 1.4 g/dL), while platelet and white blood cell counts were normal. Although performed in only three of the index subjects, serum erythropoietin concentrations determined by both radioimmune and functional assays were significantly higher in polycythemic patients compared with first-degree family members with normal hemoglobin concentrations. Southern blot analysis of the Bgl 2 erythropoietin gene polymorphism showed that one polycythemic subject was a heterozygote, suggesting the absence of linkage of polycythemia with the erythropoietin gene, assuming autosomal recessive inheritance. Polymerase chain reaction (PCR) amplification of the GGAA and GA minisatellite polymorphic regions of the erythropoietin receptor gene showed no evidence of linkage of phenotype with this gene. We conclude that Chuvash polycythemia may represent a secondary form of familial and congenital polycythemia of as yet unknown etiology. This condition is the only endemic form of familial and congenital polycythemia described.
Topics: Adolescent; Adult; Child; Erythropoietin; Female; Genes; Hemoglobins; Humans; Male; Middle Aged; Minisatellite Repeats; Pedigree; Polycythemia; Receptors, Erythropoietin; Russia
PubMed: 9058738
DOI: No ID Found -
British Medical Journal (Clinical... Jun 1986
Topics: Alcohol Drinking; Carboxyhemoglobin; Humans; Polycythemia; Smoking
PubMed: 3087541
DOI: 10.1136/bmj.292.6536.1617 -
Annals of Family Medicine 2023Gender-affirming hormone therapy (GAHT) is safe overall, with few adverse effects. One potential effect from using testosterone for GAHT is an increase in hemoglobin...
PURPOSE
Gender-affirming hormone therapy (GAHT) is safe overall, with few adverse effects. One potential effect from using testosterone for GAHT is an increase in hemoglobin and/or hematocrit, known as secondary erythrocytosis. Current guidelines recommend monitoring hemoglobin or hematocrit routinely in the first year, some as frequently as every 3 months, which can create barriers to care. Our study explored the incidence of erythrocytosis in the first 20 months of testosterone therapy among people receiving gender-affirming care.
METHODS
This is a descriptive fixed cohort study of hematocrit and hemoglobin data from the charts of 282 people taking testosterone for GAHT.
RESULTS
During the first 20 months of testosterone therapy, the cumulative incidence of hematocrit >50.4% was 12.6%, hematocrit >52% was 1.0%, and hematocrit >54% was 0.6%. All people were taking injectable testosterone cypionate, with a median dose of 100 mg weekly.
CONCLUSION
Severe erythrocytosis (hematocrit >54%) is a rare outcome of gender-affirming testosterone therapy. Clinical recommendations should reconsider the need for routine frequent erythrocytosis screening within the first year of testosterone therapy for patients who prefer to minimize laboratory draws.
Topics: Humans; Polycythemia; Cohort Studies; Testosterone; Drug-Related Side Effects and Adverse Reactions; Hemoglobins
PubMed: 37748907
DOI: 10.1370/afm.3018 -
Blood Transfusion = Trasfusione Del... Jan 2014
Review
Topics: Anemia, Sickle Cell; Biopsy; Complementary Therapies; Diagnosis, Differential; Erythropoietin; Hemochromatosis; Hepatitis C, Chronic; Humans; Iron; Kidney Transplantation; Liver; Metabolic Syndrome; Phlebotomy; Polycythemia; Polycythemia Vera; Porphyria Cutanea Tarda; Postoperative Complications
PubMed: 24120605
DOI: 10.2450/2013.0299-12 -
International Journal of Laboratory... Apr 2019Erythrocytosis is characterized by the expansion of erythrocyte compartment including elevated red blood cell number, hematocrit, and hemoglobin content. Familial... (Review)
Review
OBJECTIVES
Erythrocytosis is characterized by the expansion of erythrocyte compartment including elevated red blood cell number, hematocrit, and hemoglobin content. Familial erythrocytosis (FE) is a congenital disorder with different genetic background. Type 1 FE is primary FE caused by mutation in erythropoietin receptor gene (EPOR). Type 2-5 FE are secondary FEs caused by mutations of genes involved in oxygen sensing pathway important for erythropoietin (EPO) regulation. In the present study, we summarized associations between EPOR and EPO gene variations with development of FE and searched for genetic variants located within regulatory regions.
METHODS
Publications reporting EPOR and EPO sequence variants associated with FE or clinical features of erythrocytosis were retrieved from PubMed and WoS. In silico, sequence reanalysis was performed using Ensembl genomic browser, release 89 to screen for variants located within regulatory regions.
RESULTS
To date, 28 variants of the EPOR and seven variants of the EPO gene have been associated with erythrocytosis or upper hematocrit. Sequence variants were also found to be present within regulatory regions.
CONCLUSIONS
Role of variants in regulatory regions of the EPO gene should be further investigated.
Topics: Erythropoietin; Female; Genetic Variation; Humans; Male; Polycythemia; Receptors, Erythropoietin
PubMed: 30507031
DOI: 10.1111/ijlh.12949 -
Journal of Nuclear Medicine : Official... Aug 2017Pheochromocytoma/paraganglioma (PPGL) syndromes associated with polycythemia have previously been described in association with mutations in the von Hippel-Lindau gene....
Pheochromocytoma/paraganglioma (PPGL) syndromes associated with polycythemia have previously been described in association with mutations in the von Hippel-Lindau gene. Recently, mutations in the prolyl hydroxylase gene () 1 and 2 and in the hypoxia-inducible factor 2 α () were also found to be associated with multiple and recurrent PPGL. Such patients also presented with PPGL and polycythemia, and later on, some presented with duodenal somatostatinoma. In additional patients presenting with PPGL and polycythemia, no further mutations have been discovered. Because the functional imaging signature of patients with PPGL-polycythemia syndromes is still unknown, and because these tumors (in most patients) are multiple, recurrent, and metastatic, the goal of our study was to assess the optimal imaging approach using 4 different PET radiopharmaceuticals and CT/MRI in these patients. Fourteen patients (10 women, 4 men) with confirmed PPGL and polycythemia prospectively underwent Ga-DOTATATE (13 patients), F-FDG (13 patients), F-fluorodihydroxyphenylalanine (F-FDOPA) (14 patients), F-fluorodopamine (F-FDA) (11 patients), and CT/MRI (14 patients). Detection rates of PPGL lesions were compared between all imaging studies and stratified between the underlying mutations. F-FDOPA and F-FDA PET/CT showed similar combined lesion-based detection rates of 98.7% (95% confidence interval [CI], 92.7%-99.8%) and 98.3% (95% CI, 90.9%-99.7%), respectively. The detection rates for Ga-DOTATATE (35.3%; 95% CI, 25.0%-47.2%), F-FDG (42.3; 95% CI, 29.9%-55.8%), and CT/MRI (60.3%; 95% CI, 48.8%-70.7%) were significantly lower ( < 0.01), irrespective of the mutation status. F-FDOPA and F-FDA are superior to F-FDG, Ga-DOTATATE, and CT/MRI and should be the radiopharmaceuticals of choice in this rare group of patients.
Topics: Adolescent; Adult; Child; Female; Humans; Male; Middle Aged; Multimodal Imaging; Paraganglioma; Polycythemia; Young Adult
PubMed: 28336782
DOI: 10.2967/jnumed.116.187690