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American Journal of Hematology Aug 2023Obstructive sleep apnea (OSA) causes intermittent hypoxia during sleep. Hypoxia predictably initiates an increase in the blood hemoglobin concentration (Hb); yet in our...
Obstructive sleep apnea (OSA) causes intermittent hypoxia during sleep. Hypoxia predictably initiates an increase in the blood hemoglobin concentration (Hb); yet in our analysis of 527 patients with OSA, >98% did not have an elevated Hb. To understand why patients with OSA do not develop secondary erythrocytosis due to intermittent hypoxia, we first hypothesized that erythrocytosis occurs in these patients, but is masked by a concomitant increase in plasma volume. However, we excluded that explanation by finding that the red cell mass was normal (measured by radionuclide labeling of erythrocytes and carbon monoxide inhalation). We next studied 45 patients with OSA before and after applying continuous positive airway pressure (CPAP). We found accelerated erythropoiesis in these patients (increased erythropoietin and reticulocytosis), but it was offset by neocytolysis (lysis of erythrocytes newly generated in hypoxia upon return to normoxia). Parameters of neocytolysis included increased reactive oxygen species from expanded reticulocytes' mitochondria. The antioxidant catalase was also downregulated in these cells from hypoxia-stimulated microRNA-21. In addition, inflammation-induced hepcidin limited iron availability for erythropoiesis. After CPAP, some of these intermediaries diminished but Hb did not change. We conclude that in OSA, the absence of significant increase in red cell mass is integral to the pathogenesis, and results from hemolysis via neocytolysis combined with inflammation-mediated suppression of erythropoiesis.
Topics: Humans; Reactive Oxygen Species; Polycythemia; Hepcidins; Hypoxia; Sleep Apnea, Obstructive; Inflammation
PubMed: 37350302
DOI: 10.1002/ajh.26992 -
European Journal of Heart Failure Dec 2022Many patients with heart failure have an iron-deficient state, which can limit erythropoiesis in erythroid precursors and ATP production in cardiomyocytes. Yet,... (Review)
Review
How can sodium-glucose cotransporter 2 inhibitors stimulate erythrocytosis in patients who are iron-deficient? Implications for understanding iron homeostasis in heart failure.
Many patients with heart failure have an iron-deficient state, which can limit erythropoiesis in erythroid precursors and ATP production in cardiomyocytes. Yet, treatment with sodium-glucose cotransporter 2 (SGLT2) inhibitors produces consistent increases in haemoglobin and haematocrit, even in patients who are iron-deficient before treatment, and this effect remains unattenuated throughout treatment even though SGLT2 inhibitors further aggravate biomarkers of iron deficiency. Heart failure is often accompanied by systemic inflammation, which activates hepcidin, thus impairing the duodenal absorption of iron and the release of iron from macrophages and hepatocytes, leading to a decline in circulating iron. Inflammation and oxidative stress also promote the synthesis of ferritin and suppress ferritinophagy, thus impairing the release of intracellular iron stores and leading to the depletion of bioreactive cytosolic Fe . By alleviating inflammation and oxidative stress, SGLT2 inhibitors down-regulate hepcidin, upregulate transferrin receptor protein 1 and reduce ferritin; the net result is to increase the levels of cytosolic Fe available to mitochondria, thus enabling the synthesis of heme (in erythroid precursors) and ATP (in cardiomyocytes). The finding that SGLT2 inhibitors can induce erythrocytosis without iron supplementation suggests that the abnormalities in iron diagnostic tests in patients with mild-to-moderate heart failure are likely to be functional, rather than absolute, that is, they are related to inflammation-mediated trapping of iron by hepcidin and ferritin, which is reversed by treatment with SGLT2 inhibitors. An increase in bioreactive cytosolic Fe is also likely to augment mitochondrial production of ATP in cardiomyocytes, thus retarding the progression of heart failure. These effects on iron metabolism are consistent with (i) proteomics analyses of placebo-controlled trials, which have shown that biomarkers of iron homeostasis represent the most consistent effect of SGLT2 inhibitors; and (ii) statistical mediation analyses, which have reported striking parallelism of the effect of SGLT2 inhibitors to promote erythrocytosis and reduce heart failure events.
Topics: Humans; Adenosine Triphosphate; Biomarkers; Ferritins; Heart Failure; Hepcidins; Homeostasis; Inflammation; Iron; Polycythemia; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 36377108
DOI: 10.1002/ejhf.2731 -
Current Vascular Pharmacology 2023Twin pregnancy is associated with an increased risk of perinatal and maternal complications, and early establishment of the chorionicity type defines this risk. In... (Review)
Review
Twin pregnancy is associated with an increased risk of perinatal and maternal complications, and early establishment of the chorionicity type defines this risk. In monochorionic (MC) pregnancies, the fetuses share the same placental mass and exhibit vascular anastomoses crossing the intertwin membrane, and the combination and pattern of anastomoses determine the primary clinical picture and occurrence of future complications. Twin Anemia-Polycythemia Sequence (TAPS) was first described in 2006 after fetoscopic laser surgery in twin-to-twin transfusion syndrome (TTTS) twins, and in 2007, the first spontaneous cases were reported, recognizing TAPS as an individualized vascular identity in fetofetal transfusion syndromes. There are two types of TAPS: spontaneous (3-5%) and iatrogenic or postlaser (2-16%). TAPS consists of small diameter arteriovenous anastomoses (<1 mm) and low-rate, small-caliber AA anastomoses in the absence of amniotic fluid discordances. There are certain antenatal and postnatal diagnostic criteria, which have progressively evolved over time. New, additional secondary markers have been proposed, and their reliability is being studied. The best screening protocol for TAPS in MC twins is still a matter of debate. This review provides a survey of the relevant literature on the epidemiology, vascular pathophysiology, underlying hemodynamic factors that regulate mismatched vascular connections, and diagnostic criteria of this condition. The aim is to increase awareness and knowledge about this recently identified and frequently unrecognized and misdiagnosed pathology.
Topics: Pregnancy; Female; Humans; Placenta; Polycythemia; Reproducibility of Results; Fetofetal Transfusion; Pregnancy, Twin
PubMed: 36718965
DOI: 10.2174/1570161121666230131112930 -
Data in Brief Oct 2023Tumorous cancer has been a widely known and well-studied medical phenomenon; however, rare diseases like Myeloproliferative Neoplasm (MPN) have received less attention,...
Tumorous cancer has been a widely known and well-studied medical phenomenon; however, rare diseases like Myeloproliferative Neoplasm (MPN) have received less attention, leading to delayed diagnosis. Despite the availability of advanced technology in diagnostic tools that can boost the procedure, the morphological assessment of bone marrow trephine (BMT) images remains critical to confirm and differentiate MPN subtypes. This paper reports a histopathological imagery dataset that was created to focus on the most common MPN from the Philadelphia Chromosome (Ph)-negative type, namely Essential Thrombocythemia (ET), Polycythemia Vera (PV), and Primary Myelofibrosis (MF). The dataset consisted of 300 BMT images that can be used to enable computer vision applications, such as image segmentation, disease classification, and object recognition, in assisting the classification of the MPN disease. Ethical approval was obtained from the Ministry of Health, Malaysia and the bone marrow trephine images were captured using a digital microscope from the Olympus model (BX41 Dual head microscope) with x10, x20, and x40 lens types. The development of comprehensive tools deployed from this dataset can assist medical practitioners in diagnosing diseases, thus overcoming the current challenges.
PubMed: 37636134
DOI: 10.1016/j.dib.2023.109484 -
BMC Pulmonary Medicine Jul 2021Secondary polycythemia is associated with cigarette smoking and chronic obstructive pulmonary disease (COPD). However, the prevalence of polycythemia in COPD and the... (Observational Study)
Observational Study
BACKGROUND
Secondary polycythemia is associated with cigarette smoking and chronic obstructive pulmonary disease (COPD). However, the prevalence of polycythemia in COPD and the contributing risk factors for polycythemia in COPD have not been extensively studied.
METHODS
We analyzed the presence of secondary polycythemia in current and former smokers with moderate to very severe COPD at the five-year follow-up visit in the observational COPDGene study. We used logistic regression to evaluate the association of polycythemia with age, sex, race, altitude, current smoking status, spirometry, diffusing capacity for carbon monoxide (DLCO), quantitative chest CT measurements (including emphysema, airway wall thickness, and pulmonary artery to aorta diameter ratio), resting hypoxemia, exercise-induced hypoxemia, and long-term oxygen therapy.
RESULTS
In a total of 1928 COPDGene participants with moderate to very severe COPD, secondary polycythemia was found in 97 (9.2%) male and 31 (3.5%) female participants. In a multivariable logistic model, severe resting hypoxemia (OR 3.50, 95% CI 1.41-8.66), impaired DLCO (OR 1.28 for each 10-percent decrease in DLCO % predicted, CI 1.09-1.49), male sex (OR 3.60, CI 2.20-5.90), non-Hispanic white race (OR 3.33, CI 1.71-6.50), current smoking (OR 2.55, CI 1.49-4.38), and enrollment in the Denver clinical center (OR 4.42, CI 2.38-8.21) were associated with higher risk for polycythemia. In addition, continuous (OR 0.13, CI 0.05-0.35) and nocturnal (OR 0.46, CI 0.21-0.97) supplemental oxygen were associated with lower risk for polycythemia. Results were similar after excluding participants with anemia and participants enrolled at the Denver clinical center.
CONCLUSIONS
In a large cohort of individuals with moderate to very severe COPD, male sex, current smoking, enrollment at the Denver clinical center, impaired DLCO, and severe hypoxemia were associated with increased risk for secondary polycythemia. Continuous or nocturnal supplemental oxygen use were associated with decreased risk for polycythemia.
Topics: Aged; Aged, 80 and over; Carbon Monoxide; Cigarette Smoking; Cross-Sectional Studies; Female; Humans; Hypoxia; Logistic Models; Male; Middle Aged; Oxygen Inhalation Therapy; Polycythemia; Prevalence; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Risk Factors; Severity of Illness Index; Sex Factors; Spirometry; Tomography, X-Ray Computed; United States
PubMed: 34261472
DOI: 10.1186/s12890-021-01585-5 -
Tropical Animal Health and Production Mar 2022The study aimed to investigate if vegetable-based high-energy mash diets supplemented with NaHCO, L-arginine + vitamin C, and vegetable oils were effective against...
The study aimed to investigate if vegetable-based high-energy mash diets supplemented with NaHCO, L-arginine + vitamin C, and vegetable oils were effective against tachycardia and polycythemia in the broiler chicken. A total of 256 Ross-308 day-old male broiler chicks were randomly distributed into eight dietary treatment groups in a three-way ANOVA with 2 × 2 × 2 factorial arrangement (three factors, i.e., NaHCO, L-arginine + vitamin C, and vegetable oil each with two levels, e.g., 0 and 0.1% of NaHCO and L-arginine + vitamin C; 3 and 4% of vegetable oil supplemented with basal diet) for a period of 35 days. Iso-caloric and iso-nitrogenous diets were formulated and supplied ad libitum. The final live weight (FLW), average daily feed intake (ADFI), average daily gain (ADG), feed efficiency (FE), carcass traits, cardio-pulmonary morphometry, total protein (TP), hemoglobin (Hb), triiodothyronine (T), incidence of tachycardia, and polycythemia were examined. Supplementation of NaHCO increased 2.2% ADFI, 5.5% FE, and 23.2% TP. The L-arginine + vitamin C increased 2.4% FLW and decreased 1.9% heart rate. Vegetable oil increased 1.3% ADFI, 4.2% ADG, 8.6% FE, 23.1% Hb, and 15.5% PCV. The NaHCO, L-arginine + vitamin C, and vegetable oil additively interacted to increase 31.5% T at the expense of 21.1% of the weight of the right ventricle (RV). The RV:TV, carcass traits, and hemato-biochemical indices remained within normal range irrespective of the levels of the supplementations of the test ingredients. It was concluded that vegetable-based high-energy mash diets were not susceptible to tachycardia and polycythemia. The addition of NaHCO and L-arginine + vitamin C ameliorated the propensity of tachycardia and polycythemia without deteriorating performance, carcass traits, and hemato-biochemical indices of the broiler chicken in a dose-dependent manner.
Topics: Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Arginine; Ascorbic Acid; Chickens; Diet; Dietary Supplements; Polycythemia; Tachycardia; Vegetables
PubMed: 35233685
DOI: 10.1007/s11250-021-02993-9 -
American Journal of Perinatology Jul 2021This study aimed to test whether neonatal hypoglycemia (NH) is more common in infants with neonatal polycythemia (NP).
OBJECTIVE
This study aimed to test whether neonatal hypoglycemia (NH) is more common in infants with neonatal polycythemia (NP).
STUDY DESIGN
This is a retrospective study based on universal screening of NH and targeted screening for NP. Polycythemia was defined as venous hematocrit ≥ 65%. NH was defined as whole blood glucose (BG) concentration < 48 mg/dL (measured using a "point-of-care" analyzer [Accu-Chek]).
RESULTS
The study population consisted of 119 consecutive term polycythemic infants and 117 controls. There were no significant differences between the two groups in perinatal characteristics, minimal BG concentration, and rate of hypoglycemia. In a stepwise backward multiple regression where NH was the dependent variable, only maternal gestational diabetes mellitus ( = 0.032) and toxemia ( = 0.001) remained significant, whereas NP was insignificant.
CONCLUSION
NH is not more common in NP infants than in non-NP infants. We suggest that the occurrence of NH in infants with NP might be related to the common risk factors of the two morbidities.
Topics: Case-Control Studies; Diabetes, Gestational; Female; Hematocrit; Humans; Hypoglycemia; Infant, Newborn; Male; Polycythemia; Pre-Eclampsia; Pregnancy; Retrospective Studies; Risk Factors
PubMed: 32028531
DOI: 10.1055/s-0040-1701193 -
NEJM Evidence Jun 2023BACKGROUND: Whether phlebotomy alone can adequately maintain target hematocrit in patients with low-risk polycythemia vera (PV) remains elusive. METHODS: In a phase 2... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND: Whether phlebotomy alone can adequately maintain target hematocrit in patients with low-risk polycythemia vera (PV) remains elusive. METHODS: In a phase 2 open-label randomized trial, we compared ropeginterferon alfa-2b (ropeg; 100 μg every 2 weeks) with phlebotomy only regarding maintenance of a median hematocrit level (≤45%) over 12 months in the absence of progressive disease (primary end point). In follow-up, crossover to the alternative treatment group was allowed if the primary end point was not met. RESULTS: In total, 127 patients were enrolled (ropeg: n=64; standard group: n=63). The primary end point was met in 81% and 51% in the ropeg and standard groups, respectively. Responders continued the assigned treatment until month 24 and maintained response in 83% and 59%, respectively (P=0.02). Ropeg responders less frequently experienced moderate/severe symptoms (33% vs. 67% in the standard group) and palpable splenomegaly (14% vs. 37%) and showed normalization of ferritin levels and blood counts. Nonresponders at 12 months crossed over to the standard (n=9) or ropeg (n=23) group; in patients switched to ropeg only, 7 of 23 met the response criteria in 12 months, and phlebotomy need was high (4.7 per patient per year). Discontinuation because of adverse events occurred in seven patients treated with ropeg. CONCLUSIONS: In this 24-month trial, ropeg was superior to phlebotomy alone in maintaining hematocrit on target. No dose-limiting side effects or toxicities were noted; 9.2% of patients on ropeg and no patients on standard treatment developed neutropenia. (Funded by AOP Health and others; ClinicalTrials.gov number, NCT03003325.)
Topics: Humans; Polycythemia Vera; Polycythemia; Thrombocytosis; Thrombosis; Leukocytosis
PubMed: 38320126
DOI: 10.1056/EVIDoa2200335 -
BMC Medical Genomics Jul 2023As a chronic mountain sickness(CMS) with the highest incidence and the greatest harm, the pathogenesis of high altitude polycythemia (HAPC) is still not fully understood.
BACKGROUND
As a chronic mountain sickness(CMS) with the highest incidence and the greatest harm, the pathogenesis of high altitude polycythemia (HAPC) is still not fully understood.
METHODS
37 HAPC patients and 42 healthy subjects were selected from plateau, and peripheral venous blood samples were collected for transcriptome sequencing on Illumina NovaSeq platform. The sequenced data were analyzed by bioinformatics and phenotypic association analysis.
RESULTS
The results showed significant differences in multiple clinical indicators including RBC and HGB et al. existed between HAPC and control. Based on the RNA-seq data, 550 genes with significant differential expression were identified in HAPC patients. GO and KEGG pathway enrichment analysis showed that the up-regulated genes were mainly enriched in processes such as erythrocyte differentiation and development and homeostasis of number of cells, while the down-regulated genes were mainly enriched in categories such as immunoglobulin production, classical pathway of complement activation and other biological processes. The coupling analysis of differential expression genes(DEGs) and pathological phenotypes revealed that 91 DEGs were in close correlation with in the phenotype of red blood cell volume distribution (width-CV and width-SD), and they were all up-regulated in HAPC and involved in the process of erythrocyte metabolism. Combined with the functional annotation of DEGs and literature survey, we found that the expression of several potential genes might be responsible for pathogenesis of HAPC. Besides, cell type deconvolution analysis result suggested that the changes in the number of some immune cell types was significantly lower in HAPC patients than control, implying the autoimmune level of HAPC patients was affected to a certain extent.
CONCLUSION
This study provides an important data source for understanding the pathogenesis and screening pathogenic genes of HAPC. We found for the first time that there was a significant correlation between HAPC and the pathological phenotype of width-CV and width-SD, wherein the enriched genes were all up-regulated expressed and involved in the process of erythrocyte metabolism. Although the role of these genes needs to be further studied, the candidate genes can provide a starting point for functionally pinning down the underlying mechanism of HAPC.
Topics: Humans; Altitude Sickness; Altitude; Polycythemia; Erythrocytes
PubMed: 37507679
DOI: 10.1186/s12920-023-01613-9 -
Journal of Nephrology Jul 2022
Topics: Carcinoma, Renal Cell; Erythropoietin; Humans; Kidney Diseases, Cystic; Kidney Neoplasms; Polycythemia
PubMed: 35013984
DOI: 10.1007/s40620-021-01215-7