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Frontiers in Endocrinology 2022TEMPI (telangiectasias, elevated erythropoietin level and erythrocytosis, monoclonal gammopathy, perinephric fluid collections, and intrapulmonary shunting) syndrome is... (Review)
Review
TEMPI (telangiectasias, elevated erythropoietin level and erythrocytosis, monoclonal gammopathy, perinephric fluid collections, and intrapulmonary shunting) syndrome is a rare and newly defined multisystemic disease, which belongs to "monoclonal gammopathy of clinical significances". Due to its rarity, the etiology, pathogenesis, and clinical features of this disease remain largely unknown. Owing to its hidden and diverse clinical manifestations, missed diagnosis and misdiagnosis are common. In recent years, as more patients (including three fatal cases) were identified, some special clinical manifestations other than the typical pentad of TEMPI syndrome have been reported. Meanwhile, several studies attempting to identify the pathogenesis of TEMPI syndrome were conducted. In this review, we summarize the reported clinical characteristics of TEMPI syndrome and discuss the current and potential treatment options for patients with TEMPI syndrome, including those with relapsed/refractory disease. Furthermore, we provide an overview of current knowledge on the pathophysiology of TEMPI syndrome.
Topics: Humans; Monoclonal Gammopathy of Undetermined Significance; Paraproteinemias; Polycythemia; Syndrome; Telangiectasis
PubMed: 35663307
DOI: 10.3389/fendo.2022.886961 -
EBioMedicine Jan 2022Erythrocytosis is a hematological disorder usually related to hematopoietic stem cell somatic mutations. However, unexplained erythrocytosis remains frequent. In this...
BACKGROUND
Erythrocytosis is a hematological disorder usually related to hematopoietic stem cell somatic mutations. However, unexplained erythrocytosis remains frequent. In this study, we evaluated the involvement of IgA1, a regulator of erythropoiesis also implicated in IgA nephropathy (IgAN) pathophysiology, in unexplained polycythemia/erythrocytosis (PE) of IgAN patients.
METHODS
IgAN-PE patients' serum was collected, analyzed and used to study IgA1 effect on proliferation and differentiation of erythroid progenitors. Hematological parameters of transgenic mice for human alpha1 heavy chain were studied. Multicentric observational cohorts of chronic kidney disease (CKD) patients, including both native kidney diseases and renal transplants, were studied to analyze patient hemoglobin levels.
FINDINGS
We retrospectively identified 6 patients with IgAN and unexplained PE. In large CKD cohorts, IgAN was associated with PE in 3.5% of patients (p<0.001 compared to other nephropathies). IgAN was an independent factor associated with higher hemoglobin levels (13.1g/dL vs 12.2 g/dL, p=0.01). During post-transplant anemia, anemia recovery was faster in IgAN patients. Elevated polymeric/monomeric IgA1 ratio as well as high Gd-IgA1 rate were observed in circulating IgA1 of the 6 IgAN-PE patients as compared with control or IgAN patients without PE. IgA1 from these patients increased the sensitivity of erythroid progenitors to Epo. In mice, we also observed an elevation of hematocrit in alpha1 knock-in mice compared to wild type controls.
INTERPRETATION
These data identify a new etiology of erythrocytosis and demonstrate the role of pIgA1 in human erythropoiesis. This syndrome of IgA-related erythrocytosis should be investigated in case of unexplained erythrocytosis and renal disease.
FUNDING
This work was supported by INSERM (French national institute for health and medical research), Labex GRex and Imagine Institute (Paris, France).
Topics: Animals; Biomarkers; Galactose; Glomerulonephritis, IGA; Humans; Immunoglobulin A; Mice; Polycythemia; Retrospective Studies
PubMed: 34959131
DOI: 10.1016/j.ebiom.2021.103785 -
Clinical Obstetrics and Gynecology Sep 2015Although monochorionic (MC) twins comprise only 20% of all twin pregnancies, the risk for fetal loss and long-term morbidity is significantly higher than dichorionic... (Review)
Review
Although monochorionic (MC) twins comprise only 20% of all twin pregnancies, the risk for fetal loss and long-term morbidity is significantly higher than dichorionic twins due to the presence of placental vascular anastomoses. MC twins are at risk for multiple unique complications including twin-twin transfusion syndrome, selective intrauterine growth restriction, twin anemia-polycythemia sequence, and twin reversed arterial perfusion sequence. Discordant anomalies can negatively impact the outcome for the normal cotwin. It is imperative that early determination of chorionicity is established such that the appropriate surveillance is in place to identify MC complications to optimize outcomes.
Topics: Anemia; Chorion; Female; Fetal Growth Retardation; Fetofetal Transfusion; Humans; Polycythemia; Pregnancy; Pregnancy, Twin; Twins, Monozygotic; Ultrasonography
PubMed: 26176787
DOI: 10.1097/GRF.0000000000000127 -
Pediatric Clinics of North America Apr 2015"Common red blood cell disorders encountered in the normal newborn nursery include hemolytic disease of the newborn and resultant hyperbilirubinemia, anemia, and... (Review)
Review
"Common red blood cell disorders encountered in the normal newborn nursery include hemolytic disease of the newborn and resultant hyperbilirubinemia, anemia, and polycythemia. A less frequent clinically relevant hematologic issue in newborns to be covered herein is thrombocytopenia."
Topics: Erythroblastosis, Fetal; Glucosephosphate Dehydrogenase Deficiency; Hematologic Diseases; Hemoglobinopathies; Hemolysis; Humans; Hyperbilirubinemia; Infant, Newborn; Isoantibodies; Polycythemia; Thrombocytopenia
PubMed: 25836711
DOI: 10.1016/j.pcl.2014.11.011 -
The Journal of Endocrinology Sep 2023Testosterone acting via the androgen receptor, and via aromatisation to oestradiol, an activator of the oestrogen receptor, plays key roles in adipose tissue, bone and...
Testosterone acting via the androgen receptor, and via aromatisation to oestradiol, an activator of the oestrogen receptor, plays key roles in adipose tissue, bone and skeletal muscle biology. This is reflected in epidemiological studies associating obesity and disordered glucose metabolism with lower serum testosterone concentrations and an increased risk of type 2 diabetes (T2D) in men. Testosterone also modulates erythrocytosis and vascular endothelial and smooth muscle cell function, with potential impacts on haematocrit and the cardiovascular system. The Testosterone for the Prevention of Type 2 Diabetes (T4DM) study enrolled men aged 50 years and over with a waist circumference of 95 cm or over, impaired glucose tolerance or newly diagnosed T2D, and a serum testosterone concentration (as measured by chemiluminescence immunoassay) <14.0 nmol/L. The study reported that a 2-year treatment with testosterone undecanoate 1000 mg, administered 3-monthly intramuscularly, on the background of a lifestyle program, reduced the likelihood of T2D diagnosis by 40% compared to placebo. This effect was accompanied by a decrease in fasting serum glucose and associated with favourable changes in body composition, hand grip strength, bone mineral density and skeletal microarchitecture but not in HbA1c, a red blood cell-dependent measure of glycaemic control. There was no signal for cardiovascular adverse events. With the objective of informing translational science and future directions, this article discusses mechanistic studies underpinning the rationale for T4DM and translational implications of the key outcomes relating to glycaemia, and body composition, together with effects on erythrocytosis, cardiovascular risk and slow recovery of the hypothalamo-pituitary-testicular axis.
Topics: Male; Humans; Middle Aged; Aged; Diabetes Mellitus, Type 2; Polycythemia; Hand Strength; Testosterone; Obesity
PubMed: 37227171
DOI: 10.1530/JOE-22-0223 -
Blood Transfusion = Trasfusione Del... Nov 2021Erythrocytosis is a blood disorder characterised by an increased red blood cell mass. The most common causes of erythrocytosis are acquired and caused by diseases and... (Review)
Review
Erythrocytosis is a blood disorder characterised by an increased red blood cell mass. The most common causes of erythrocytosis are acquired and caused by diseases and conditions that are accompanied by hypoxaemia or overproduction of erythropoietin. More rarely, erythrocytosis has a known genetic background, such as for polycythaemia vera and familial erythrocytosis. The majority of cases of polycythaemia vera are associated with acquired variants in JAK2, while familial erythrocytosis is a group of congenital disorders. Familial erythrocytosis type 1 is associated with hypersensitivity to erythropoietin (variants in EPOR), types 2-5 with defects in oxygen-sensing pathways (variants in VHL, EGLN1, EPAS1, EPO), and types 6-8 with an increased affinity of haemoglobin for oxygen (variants in HBB, HBA1, HBA2, BPGM). Due to a heterogenic genetic background, the causes of disease are not fully discovered and in more than 70% of patients the condition remains labelled idiopathic.The transfer of next-generation sequencing into clinical practice is becoming a reality enabling detection of various variants in a single rapid test. In this review, we describe the current research on erythrocytosis gene variants and the mechanisms associated with disease development, along with the currently used diagnostic tests.
Topics: Erythropoietin; Hemoglobins; Humans; Mutation; Oxygen; Polycythemia
PubMed: 33370224
DOI: 10.2450/2020.0197-20 -
Hematology (Amsterdam, Netherlands) Dec 2023Polycythemia vera (PV) is classically thought to be associated with low erythropoietin (EPO) levels. Here, we present a review of the utility of using EPO levels in...
OBJECTIVES
Polycythemia vera (PV) is classically thought to be associated with low erythropoietin (EPO) levels. Here, we present a review of the utility of using EPO levels in diagnosing polycythemia.
METHODS
We conducted a systematic literature review of the Medline data through Pubmed and Google Scholar. We included the articles which described confirmed PV associated with elevated EPO level. Our search strategy included the following terms in Pubmed (((polycythemia vera[MeSH Terms]) OR (jak2 protein tyrosine kinase[MeSH Terms])) OR (Myeloproliferative Disorders[MeSH Terms])) AND (Erythropoietin[MeSH Terms]), and 'polycythemia vera with erythropoietin' in Google Scholar.
RESULTS
Our research yielded four cases of PV with elevated EPO levels. The most common symptom was a headache. Thrombotic phenomena happened in a single case in the form of Budd-Chiari syndrome. The mean Hb level was 20.2 gm/dl, and the EPO level was 213 mlU/mL.
DISCUSSION
Although PV is usually associated with low EPO levels, high levels do not exclude this diagnosis. Workup should include testing for JAK2 mutation and bone marrow biopsy in the presence of suggestive signs and symptoms. Novel biomarkers are also being proposed to aid in the diagnosis.
CONCLUSION
Although elevated EPO levels suggest secondary causes of polycythemia, cases where elevated EPO levels were associated with an underlying PV are reported in the literature, and we have summarized a review of them. Workup for polycythemia should include JAK2 mutation testing if signs and symptoms suggest PV even if EPO is elevated.
Topics: Humans; Polycythemia; Polycythemia Vera; Janus Kinase 2; Bone Marrow; Erythropoietin
PubMed: 37843428
DOI: 10.1080/16078454.2023.2269510 -
Current Hematologic Malignancy Reports Jun 2018The purpose of this review is to help doctors in the management of patients with post-polycythemia (PPV) and post-essential thrombocythemia (PET) myelofibrosis (MF)... (Review)
Review
PURPOSE OF REVIEW
The purpose of this review is to help doctors in the management of patients with post-polycythemia (PPV) and post-essential thrombocythemia (PET) myelofibrosis (MF) facing diagnostic criteria, prognostication, and treatment possibilities.
RECENT FINDINGS
Diagnostic criteria of primary myelofibrosis (PMF) have been recently updated from the WHO classification. A clear-cut distinction between pre-fibrotic and overt PMF has been done. Concerning PPV and PET MF, the criteria come from 2008. Prognostication of PMF has been well established on clinical criteria, but recent molecular acquisitions will improve the strategy. For PPV and PET MF, the new MYSEC-PM is helpful for prediction of survival. JAK2-inhibitors and stem cell transplant are the two critical therapeutic approaches in myelofibrosis. Differences between PMF and SMF substantiate the efforts underway to adequately stratify SMF patients with ad hoc prognostic tools and to use such categorization to evaluate available treatment modalities.
Topics: Humans; Polycythemia; Primary Myelofibrosis; Prognosis; Thrombocythemia, Essential
PubMed: 29713873
DOI: 10.1007/s11899-018-0453-y -
Best Practice & Research. Clinical... Nov 2022Monochorionic twin pregnancies have an increased risk of morbidity and mortality. Due to the advancements in screening and treatment strategies, mortality rates have... (Review)
Review
Monochorionic twin pregnancies have an increased risk of morbidity and mortality. Due to the advancements in screening and treatment strategies, mortality rates have decreased. Improving survival rates demands a shift in scope toward long-term outcomes. In this review, we focus on neurodevelopmental outcome in survivors from complicated monochorionic twin pregnancies, including twin-twin transfusion syndrome (TTTS), twin anemia-polycythemia sequence (TAPS), acute peripartum TTTS, acute perimortem TTTS, selective fetal growth restriction (sFGR) and monoamnionicity. Our aim is to provide an overview of the current knowledge on the long-term outcome in survivors, including psychomotor development and quality of life, and provide recommendations for future research and follow-up programs.
Topics: Pregnancy; Female; Humans; Pregnancy, Twin; Follow-Up Studies; Quality of Life; Fetofetal Transfusion; Polycythemia
PubMed: 35491308
DOI: 10.1016/j.bpobgyn.2022.03.014 -
Kidney International Jul 2022High-altitude polycythemia (HAPC) is a clinical syndrome that occurs in native inhabitants or long-term residents living at altitude. The kidney is one of the most...
High-altitude polycythemia (HAPC) is a clinical syndrome that occurs in native inhabitants or long-term residents living at altitude. The kidney is one of the most affected organs. However, the clinical and kidney histopathological profiles of HAPC-related kidney disease have rarely been reported. Here, we report kidney biopsy-based clinicopathological study on this disease. HAPC was defined as excessive erythrocytosis [females, hemoglobin 190 g/L or more; males, 210 g/L or more] in patients living above an altitude of 2500 m for more than ten years. A total of 416 Tibetan patients underwent kidney biopsy between January 1, 2016, and November 31, 2020. Of these patients 17 met the diagnostic criteria for HAPC-related kidney disease. Clinically, these patients had a median urinary protein level of 2.5 g/24-hour (range 1.81-6.85). Twelve patients had hyperuricemia, nine had hypertension, and three had kidney insufficiency. On histopathology, glomerular hypertrophy, glomerular basement membrane thickening, podocyte foot process effacement, segmental glomerulosclerosis and global glomerulosclerosis were the main features. Extraglomerular arterial/arteriolar lesions were common, presenting as intimal fibrosis, hyalinosis and endothelial cell swelling/subintimal edema. Expansion of the arterial/arteriolar medial wall area characterized by smooth muscle cell proliferation was clearly observed, potentially indicating vascular remodeling. Hypoxia-inducible factor 2α was expressed in the kidney tissues of these patients. Thus, the pathological changes of HAPC-related kidney disease encompassed both glomerular and extraglomerular vascular lesions, suggesting a key role of both chronic hypoxia itself and secondary hemodynamic changes in the pathogenesis of this disease.
Topics: Altitude; Altitude Sickness; Female; Glomerulosclerosis, Focal Segmental; Humans; Hypoxia; Male; Polycythemia; Tibet
PubMed: 35513124
DOI: 10.1016/j.kint.2022.03.027