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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 -
Journal of Veterinary Internal Medicine Jul 2022Prolonged tissue hypoxia caused by chronic pulmonary disease is commonly regarded as an important mechanism in the development of secondary polycythemia, but little...
BACKGROUND
Prolonged tissue hypoxia caused by chronic pulmonary disease is commonly regarded as an important mechanism in the development of secondary polycythemia, but little clinical data are available to support this hypothesis.
OBJECTIVE
To study the prevalence and severity of erythrocytosis accompanying chronic hypoxic pulmonary disease in dogs.
ANIMALS
Forty-seven dogs with hypoxic chronic pulmonary disease, 27 dogs with nonhypoxic chronic pulmonary disease, and 60 healthy controls.
METHODS
Dogs with chronic pulmonary disease and chronic hypoxemia (partial pressure of arterial oxygen [PaO ] < 80 mm Hg on at least 2 arterial blood gas measurements a minimum of 1 month apart) were identified retrospectively from patient records. Association between arterial oxygen and red blood cell parameters was analyzed using Pearson's correlation coefficients and multivariable linear regression analysis.
RESULTS
Red blood cell parameters measured at the end of the hypoxemia period were within the laboratory reference range in most dogs. In chronically hypoxemic dogs, hematocrit (Hct) was increased in 4/47 (8.5%; 95% confidence interval [CI], 0-17) dogs, erythrocyte count (Erytr) was increased in 12/47 (26%; 95%CI, 13-38) dogs and hemoglobin concentration (Hb) was increased in 3/47 (6.4%; 95%CI, 0-14) dogs. No marked polycythemia (Hct ≥65%) was noted in any of the dogs. Red blood cell parameters were not associated with the severity of hypoxemia (correlation to PaO : Erytr, r = -.14; Hb, r = -.21; Hct, r = -.14; P > .05 for all).
CONCLUSIONS AND CLINICAL IMPORTANCE
Polycythemia is uncommon, and usually mild if present, in dogs with chronic hypoxia caused by pulmonary disease.
Topics: Animals; Dog Diseases; Dogs; Hypoxia; Lung Diseases; Oxygen; Polycythemia; Retrospective Studies
PubMed: 35702817
DOI: 10.1111/jvim.16466 -
Blood Aug 2013Organisms living under aerobic conditions need oxygen for the metabolic conversion of nutrition into energy. With the appearance of increasingly complex animals, a... (Review)
Review
Organisms living under aerobic conditions need oxygen for the metabolic conversion of nutrition into energy. With the appearance of increasingly complex animals, a specialized transport system (erythrocytes) arose during evolution to provide oxygen to virtually every single cell in the body. Moreover, in case of low environmental partial pressure of oxygen, the number of erythrocytes automatically increases to preserve sustained oxygen delivery. This process relies predominantly on the cytokine erythropoietin (Epo) and its transcription factor hypoxia inducible factor (HIF), whereas the von Hippel-Lindau (VHL) ubiquitin ligase as well as the oxygen-sensitive prolyl hydroxylases (PHDs) represent essential regulators of this oxygen-sensing system. Deregulation of particular members of this pathway (eg, PHD2, HIF2α, VHL) lead to disorders in blood homeostasis as a result of insufficient (anemia) or excessive (erythrocytosis) red blood cell production.
Topics: Animals; Humans; Hypoxia-Inducible Factor 1; Polycythemia; Signal Transduction
PubMed: 23733342
DOI: 10.1182/blood-2013-01-478065 -
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 -
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 -
British Journal of Haematology Mar 2010Primary familial and congenital polycythemia (PFCP) is an autosomal-dominant proliferative disorder characterized by erythrocytosis and hypersensitivity of erythroid... (Review)
Review
Primary familial and congenital polycythemia (PFCP) is an autosomal-dominant proliferative disorder characterized by erythrocytosis and hypersensitivity of erythroid progenitors to erythropoietin (Epo). Several lines of evidence suggest a causal role of truncated erythropoietin receptor (EpoR) in this disease. In this review, we discuss PFCP in the context of erythrocytosis and EpoR signalling. We focus on recent studies describing mechanisms underlying Epo-dependent EpoR down-regulation. One mechanism depends on internalization mediated through the p85 regulatory subunit of the Phosphoinositide 3-Kinase, and the other utilizes ubiquitin-based proteasomal degradation. Truncated PFCP EpoRs are not properly down-regulated upon stimulation, underscoring the importance of these mechanisms in the pathogenesis of PFCP.
Topics: Down-Regulation; Humans; Mutation; Polycythemia; Receptors, Erythropoietin; Signal Transduction
PubMed: 20096014
DOI: 10.1111/j.1365-2141.2009.08069.x -
Beijing Da Xue Xue Bao. Yi Xue Ban =... Feb 2022To explore the relationship between high altitude polycythemia (HAPC) and peptic ulcer bleeding, in order to provide the evidence for the clinical diagnosis and...
OBJECTIVE
To explore the relationship between high altitude polycythemia (HAPC) and peptic ulcer bleeding, in order to provide the evidence for the clinical diagnosis and treatment of peptic ulcer disease in Tibet of China.
METHODS
A retrospective case-control study was conducted. Patients who hospitalized in the Department of Gastroenterology with the diagnosis of peptic ulcer bleeding from January 1, 2015 to April 30, 2021 in Tibet Autonomous Region People's Hospital were enrolled in the case group, and patients who hospitalized in the Department of Urology without tumor and without the history of peptic ulcer and gastrointestinal bleeding during the same period were selected as the control group. In the study, 1 ∶ 1 case matching was conducted between the two groups according to the gender, age (±2 years), ethnic group (Tibetan, Han), and the residence altitude level (grouped by < 4 000 m or ≥4 000 m), and 393 cases were included in the case group and the control group respectively. All the patients had lived in Tibet with the altitude >2 500 m for more than 1 year, and with age ≥ 18 years. The risk factors of peptic ulcer bleeding (place of residence, smoking, alcohol, the use of NSAIDs/anticoagulants, and combined with chronic diseases, such as HAPC, hypertension, diabetes mellitus, heart disease, hyperlipidemia, cerebrovascular disease, chronic lung disease, joint disease) were analyzed and compared between the two groups.
RESULTS
There were 28 (7.1%) patients with HAPC in the case group, and 5 (1.3%) in the control group. The incidence of HAPC in the case group was significantly higher than those in the control group, < 0.001, and the value was 5.953. Multivariate Logistic regression analysis showed that HAPC (=5.270, 95%: 1.806-15.380), living in cities and towns (=2.369, 95%: 1.559-3.602), alcohol (=3.238, 95%: 1.973-5.317) and the use of NSAIDs/anticoagulants (=20.584, 95%: 2.639-160.545) were the independent risk factors for peptic ulcer bleeding in Tibet. After adjusting for the possible confounding factors, such as living in cities and towns, alcohol, and the use of NSAIDs/anticoagulants, HAPC was associated with an increased risk of peptic ulcer bleeding in Tibet, and the value was 5.270.
CONCLUSION
HAPC was associated with a significantly increased risk of peptic ulcer bleeding in Tibet. Patients with HAPC and peptic ulcer should be diagnosed and treated actively, in order to avoid gastrointestinal bleeding and other serious complications.
Topics: Adolescent; Altitude; Case-Control Studies; Humans; Peptic Ulcer; Polycythemia; Retrospective Studies; Risk Factors
PubMed: 35165484
DOI: 10.19723/j.issn.1671-167X.2022.01.025 -
Journal of Clinical Pathology Mar 1967An English family suffering from thalassaemia minor is described. Three generations are affected, and all the affected members had a considerably raised red cell count...
An English family suffering from thalassaemia minor is described. Three generations are affected, and all the affected members had a considerably raised red cell count in the presence of slight or moderate anaemia, obviously abnormal peripheral films, and only slightly reduced M.C.H.C. values; and each had a moderately raised haemoglobin A(2) level, though foetal haemoglobin levels were normal. The presentation of a family with erythrocytosis recalls the condition described in the older literature as benign familial polycythaemia which was, in some cases at least, thalassaemia minor. It is suggested that the presence of a raised red cell count is a more reliable distinguishing feature than the presence of target cells, or the serum iron level, in thalassaemia minor.
Topics: Adult; Aged; Anemia, Hypochromic; Blood Cell Count; Child; Child, Preschool; England; Female; Hemoglobins; Humans; Male; Middle Aged; Polycythemia; Thalassemia; White People
PubMed: 5602507
DOI: 10.1136/jcp.20.2.158 -
Metabolic Syndrome and Related Disorders Jun 2023Both polycythemia and high leukocyte count are associated with the risk of cardiovascular disease. However, it remains to be determined whether polycythemia and high...
Both polycythemia and high leukocyte count are associated with the risk of cardiovascular disease. However, it remains to be determined whether polycythemia and high leukocyte count show synergistic increasing effects on cardiometabolic risk. Cardiometabolic risk was evaluated by cardiometabolic index (CMI) and metabolic syndrome in a cohort of middle-aged men ( = 11,140) who underwent annual health check-up examinations. The subjects were divided into three tertile groups by hemoglobin concentration or leukocyte count in peripheral blood, and their relations with CMI and metabolic syndrome were investigated. A new index, named hematometabolic index (HMI), was defined as the product of hemoglobin concentration (g/dL)-minus-13.0 and leukocyte count (/μL)-minus-3000. When the subjects were further classified by tertiles for hemoglobin concentration and leukocyte count into nine groups, the odds ratios for high CMI and metabolic syndrome of the group categorized in the highest (third) tertiles for both hemoglobin concentration and leukocyte count versus the group of the lowest (first) tertiles for both of them were highest among the nine groups. In receiver-operating characteristic (ROC) analysis for relationships of HMI with high CMI and metabolic syndrome, areas under the ROC curves (AUCs) were significantly larger than the reference level and tended to be smaller with an increase in age. In subjects from 30 to 39 years of age, the AUC for the relationship between HMI and metabolic syndrome was 0.707 (0.663-0.751) and the cutoff of HMI was 9850. HMI, reflecting hemoglobin concentration and leukocyte count, is thought to be a possible marker for discriminating cardiometabolic risk.
Topics: Male; Middle Aged; Humans; Metabolic Syndrome; Polycythemia; Leukocyte Count; Cardiovascular Diseases; Hemoglobins; Risk Factors
PubMed: 37196206
DOI: 10.1089/met.2023.0011 -
Fetal Diagnosis and Therapy 2020The aim of this study was to evaluate the differences in leukocyte counts at birth between donors and recipients with twin-twin transfusion syndrome (TTTS) or twin... (Comparative Study)
Comparative Study
OBJECTIVE
The aim of this study was to evaluate the differences in leukocyte counts at birth between donors and recipients with twin-twin transfusion syndrome (TTTS) or twin anemia-polycythemia sequence (TAPS).
METHODS
We performed a retrospective cohort study in monochorionic twin pairs with TTTS or TAPS. TTTS and TAPS cases treated with fetoscopic laser surgery were excluded. Primary outcome was the difference in leukocyte levels at birth between donor and recipient twins and the presence of leukopenia (defined as leukocyte count <4 × 109/L). Secondary outcomes included early-onset sepsis, necrotizing enterocolitis, use of antibiotics during admission, and neonatal mortality.
RESULTS
We included 99 twins pairs, of which 61 twin pairs were affected by TAPS and 38 twin pairs by TTTS. The mean leukocyte count at birth in donors and recipients was 7.5 × 109/L versus 7.4 × 109/L (p = 0.936), respectively. Leukopenia was significantly more common in donor twins compared to recipient twins (7.1% [7/99] vs. 0% [0/99], p = 0.016). Of the 7 donors with leukopenia, 6 were affected by TAPS and 1 by TTTS. Overall, donors were more often affected by early-onset sepsis than recipients, 23.7% (23/97) versus 13% (13.7/95) (p = 0.049), respectively.
CONCLUSIONS
Leukocyte counts at birth in twins with TTTS or TAPS are similar between donors and recipients, but TAPS donors are at an increased risk of leukopenia. Overall, TTTS and TAPS donors seem to be at an increased risk of early-onset neonatal sepsis compared to recipient twins.
Topics: Anemia; Biomarkers; Female; Fetofetal Transfusion; Humans; Infant; Infant, Newborn; Leukocyte Count; Leukopenia; Neonatal Sepsis; Polycythemia; Predictive Value of Tests; Pregnancy; Prognosis; Retrospective Studies; Risk Assessment; Risk Factors; Twins, Monozygotic
PubMed: 31261154
DOI: 10.1159/000500859