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Haematologica Oct 2018Pathological erythropoiesis with consequent anemia is a leading cause of symptomatic morbidity in internal medicine. The etiologies of anemia are complex and include... (Review)
Review
Pathological erythropoiesis with consequent anemia is a leading cause of symptomatic morbidity in internal medicine. The etiologies of anemia are complex and include reactive as well as neoplastic conditions. Clonal expansion of erythroid cells in the bone marrow may result in peripheral erythrocytosis and polycythemia but can also result in anemia when clonal cells are dysplastic and have a maturation arrest that leads to apoptosis and hinders migration, a constellation typically seen in the myelodysplastic syndromes. Rarely, clonal expansion of immature erythroid blasts results in a clinical picture resembling erythroid leukemia. Although several mechanisms underlying normal and abnormal erythropoiesis and the pathogenesis of related disorders have been deciphered in recent years, little is known about specific markers and targets through which prognosis and therapy could be improved in anemic or polycythemic patients. In order to discuss new markers, targets and novel therapeutic approaches in erythroid disorders and the related pathologies, a workshop was organized in Vienna in April 2017. The outcomes of this workshop are summarized in this review, which includes a discussion of new diagnostic and prognostic markers, the updated WHO classification, and an overview of new drugs used to stimulate or to interfere with erythropoiesis in various neoplastic and reactive conditions. The use and usefulness of established and novel erythropoiesis-stimulating agents for various indications, including myelodysplastic syndromes and other neoplasms, are also discussed.
Topics: Adult; Anemia; Erythroid Cells; Erythropoiesis; Gene Expression Regulation, Neoplastic; Humans; Neoplasms; Polycythemia
PubMed: 30076180
DOI: 10.3324/haematol.2018.192518 -
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 -
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 -
Ultrasound in Obstetrics & Gynecology :... Feb 2016Twin anemia-polycythemia sequence (TAPS) is recognized increasingly antenatally by the demonstration of an anemic twin and a polycythemic cotwin using the middle... (Review)
Review
Review of the correlation between blood flow velocity and polycythemia in the fetus, neonate and adult: appropriate diagnostic levels need to be determined for twin anemia-polycythemia sequence.
Twin anemia-polycythemia sequence (TAPS) is recognized increasingly antenatally by the demonstration of an anemic twin and a polycythemic cotwin using the middle cerebral artery peak systolic velocity (MCA-PSV). While the MCA-PSV has been shown to correlate well with anemia in singleton fetuses, the evidence to support its use to diagnose fetal polycythemia appears to be less clear-cut. We aimed to evaluate fetal, neonatal and adult literature used to support the use of MCA-PSV for the diagnosis of polycythemia. Comprehensive literature searches were performed for ultrasound evidence of polycythemia in the human fetus, neonate and adult using key search terms. Only manuscripts in the English language with an abstract were considered for the review, performed in June 2014. Fifteen manuscripts were found for the human fetus, including 38 cases of TAPS. Nine of these defined fetal polycythemia as MCA-PSV < 0.8 multiples of the median (MoM), five used < 1.0 MoM and one used 0.8-1.0 MoM. Only two studies, involving a total of 15 cases, proposed a diagnostic level, acknowledging false-positive and -negative cases, though neither reported sensitivities or specificities. Six neonatal studies (96 neonates) demonstrated evidence of decreased cerebral velocities in polycythemia and a consequent increase with hemodilution. In the adult, five studies (57 polycythemic adults) demonstrated increased flow or velocity with hemodilution. Neither neonatal nor adult studies conclusively defined levels for screening for polycythemia. Despite widespread adoption of a cut-off of < 0.8 MoM in the published literature for the polycythemic fetus in TAPS, this is based upon minimal evidence, with unknown sensitivity and specificity. We recommend caution in excluding TAPS based purely upon the absence of a reduced MCA-PSV.
Topics: Adult; Anemia; Blood Flow Velocity; Diseases in Twins; Female; Fetal Diseases; Humans; Infant, Newborn; Middle Cerebral Artery; Polycythemia; Pregnancy; Pregnancy, Twin; Reference Values; Sensitivity and Specificity; Ultrasonography, Prenatal
PubMed: 25580896
DOI: 10.1002/uog.14782 -
Expert Review of Hematology Aug 2016Twin-twin transfusion syndrome (TTTS) and twin anemia polycythemia sequence (TAPS) are severe complications in monochorionic twin pregnancies associated with high... (Review)
Review
INTRODUCTION
Twin-twin transfusion syndrome (TTTS) and twin anemia polycythemia sequence (TAPS) are severe complications in monochorionic twin pregnancies associated with high mortality and morbidity risk if left untreated. Both diseases result from imbalanced inter-twin blood transfusion through placental vascular anastomoses.
AREAS COVERED
This review focuses on the differences in antenatal management between TTTS and TAPS. Expert commentary: The optimal management for TTTS is fetoscopic laser coagulation of the vascular anastomoses, preferably using the Solomon technique in which the whole vascular equator is coagulated. The Solomon technique is associated with a reduction of residual anastomosis and a reduction in post-operative complications. The optimal management for TAPS is not clear and includes expectant management, intra-uterine transfusion with or without partial exchange transfusion and fetoscopic laser surgery.
Topics: Anemia; Blood Transfusion; Disease Management; Female; Fetofetal Transfusion; Fetoscopy; Humans; Laser Therapy; Polycythemia; Positron-Emission Tomography; Pregnancy; Pregnancy, Twin
PubMed: 27322562
DOI: 10.1080/17474086.2016.1200968 -
International Journal of Laboratory... May 2019Multiple algorithms have been published for the evaluation of hereditary erythrocytosis (HE). Typical entry points begin after excluding the more common acquired... (Review)
Review
Multiple algorithms have been published for the evaluation of hereditary erythrocytosis (HE). Typical entry points begin after excluding the more common acquired conditions through investigations of clinical history and assessment of cardiac, pulmonary, or vascular system disorders. Prior exclusion of JAK2 mutations, particularly the common JAK2 V617F mutation, is indicated in adults but less so in pediatric populations. Key decision trees are based on serum erythropoietin levels and p50 results. Recent data reveal some overlap in clinical presentation and laboratory findings in erythrocytosis. Caveats to consider when using algorithmic approaches are discussed.
Topics: Algorithms; Amino Acid Substitution; Erythropoietin; Humans; Janus Kinase 2; Mutation, Missense; Polycythemia; Signal Transduction
PubMed: 31069987
DOI: 10.1111/ijlh.13019 -
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 -
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 -
Endocrine-related Cancer Dec 2016Worldwide, the syndromes of paraganglioma (PGL), somatostatinoma (SOM) and early childhood polycythemia are described in only a few patients with somatic mutations in...
Worldwide, the syndromes of paraganglioma (PGL), somatostatinoma (SOM) and early childhood polycythemia are described in only a few patients with somatic mutations in the hypoxia-inducible factor 2 alpha (HIF2A). This study provides detailed information about the clinical aspects and course of 7 patients with this syndrome and brings into perspective these experiences with the pertinent literature. Six females and one male presented at a median age of 28 years (range 11-46). Two were found to have HIF2A somatic mosaicism. No relatives were affected. All patients were diagnosed with polycythemia before age 8 and before PGL/SOM developed. PGLs were found at a median age of 17 years (range 8-38) and SOMs at 29 years (range 22-38). PGLs were multiple, recurrent and metastatic in 100, 100 and 29% of all cases, and SOMs in 40, 40 and 60%, respectively. All PGLs were primarily norepinephrine-producing. All patients had abnormal ophthalmologic findings and those with SOMs had gallbladder disease. Computed tomography (CT) and magnetic resonance imaging revealed cystic lesions at multiple sites and hemangiomas in 4 patients (57%), previously thought to be pathognomonic for von Hippel-Lindau disease. The most accurate radiopharmaceutical to detect PGL appeared to be [F]-fluorodihydroxyphenylalanine ([F]-FDOPA). Therefore, [F]-FDOPA PET/CT, not [Ga]-(DOTA)-[Tyr3]-octreotate ([Ga]-DOTATATE) PET/CT is recommended for tumor localization and aftercare in this syndrome. The long-term prognosis of the syndrome is unknown. However, to date no deaths occurred after 6 years follow-up. Physicians should be aware of this unique syndrome and its diagnostic and therapeutic challenges.
Topics: Adolescent; Adrenal Gland Neoplasms; Adult; Child; Cohort Studies; Disease Progression; Female; Humans; Male; Middle Aged; Neoplasms, Multiple Primary; Pancreatic Neoplasms; Paraganglioma; Polycythemia; Retrospective Studies; Somatostatinoma; Syndrome; Young Adult
PubMed: 27679736
DOI: 10.1530/ERC-16-0231