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Blood Jan 2015
Topics: Adolescent; Child; Female; Humans; Male; Polycythemia; Registries; Young Adult
PubMed: 25573974
DOI: 10.1182/blood-2014-10-604660 -
BMC Ophthalmology Nov 2022Central Retinal Vein Occlusion (CRVO) is a rare complication of von Hipple-Lindau (VHL) disease. This report presents the first case of VHL disease complicated with CRVO...
BACKGROUND
Central Retinal Vein Occlusion (CRVO) is a rare complication of von Hipple-Lindau (VHL) disease. This report presents the first case of VHL disease complicated with CRVO caused by VHL c.208G > A mutation.
CASE PRESENTATION
A 20 s man whose left eye visual acuity gradually declined for half a year. The visual acuity of the left eye is counting fingers. Fundus examination revealed that retinal hemangioblastoma was also found in addition to typical CRVO signs such as tortuous expansion of retinal veins and flame-shaped hemorrhage of the retina. Liver tumor, cerebral infarction and erythrocytosis were found during systemic examination, and the diagnosis of polycythemia was confirmed by bone marrow smear. Furthermore, both family history and genetic analysis indicated that the patient had VHL disease caused by VHL c.208G > A. In this patient, a large number of bone marrow erythrocytes proliferated due to VHL disease, which led to the increase of blood viscosity and erythrocyte vascular adhesion, resulting in the obstruction of central retinal vein blood flow, and finally CRVO. For CRVO and its pathogenic factor polycythemia, patient received laser retinal photocoagulation and phlebotomies. After a 1-year follow-up, the vision in the left eye improved to 0.2 logMAR.
CONCLUSIONS
This is a rare case of polycythemia complicated by CRVO in patient with VHL disease. It reminds us that the systemic disease factors should be fully considered in the diagnosis of young patients with CRVO, and that treatment requires a coordinated effort of physicians.
Topics: Male; Humans; Retinal Vein Occlusion; von Hippel-Lindau Disease; Polycythemia; Retinal Vein; Retinal Hemorrhage
PubMed: 36384467
DOI: 10.1186/s12886-022-02661-y -
The Tohoku Journal of Experimental... Oct 1987The definite differential diagnosis between spurious polycythemia (SP) and pure erythrocytosis (PE) was tested. Serum erythropoietin (EPO) levels in 6 patients with PE...
The definite differential diagnosis between spurious polycythemia (SP) and pure erythrocytosis (PE) was tested. Serum erythropoietin (EPO) levels in 6 patients with PE were 12.8 +/- 3.7 mU/ml and were significantly lower than those of both 19 normal controls (28.5 +/- 15.0 mU/ml) and 9 patients with SP (21.3 +/- 10.2 mU/ml). Three of 11 patients with SP and 1 of 3 patients with PE had significantly higher marrow erythroid progenitor cells (CFU-Es) than those of the normal controls. Spontaneous CFU-E growth (CFU-E growth in the absence of added EPO) was found in 4 of 11 patients with SP, 1 of 3 patients with PE, and all patients with polycythemia vera. However, the number of spontaneous CFU-E was low in SP and PE. The measurements of serum EPO levels and CFU-E growth did not provide differentiation between PE and SP. Even if some patients, whose total red cell volumes are either higher than 12.5% above the mean predicted values or their CFU-E growth is great, are diagnosed as SP, consideration should be made that they might, in fact, have PE.
Topics: Adult; Aged; Bone Marrow Cells; Diagnosis, Differential; Erythrocyte Indices; Erythropoietin; Female; Hematopoietic Stem Cells; Humans; Male; Middle Aged; Polycythemia; Polycythemia Vera
PubMed: 3686523
DOI: 10.1620/tjem.153.103 -
The Journal of Clinical Investigation Apr 2018Chuvash polycythemia is an inherited disease caused by a homozygous germline VHLR200W mutation, which leads to impaired degradation of HIF2α, elevated levels of serum...
Chuvash polycythemia is an inherited disease caused by a homozygous germline VHLR200W mutation, which leads to impaired degradation of HIF2α, elevated levels of serum erythropoietin, and erythrocytosis/polycythemia. This phenotype is recapitulated by a mouse model bearing a homozygous VhlR200W mutation. We previously showed that iron-regulatory protein 1-knockout (Irp1-knockout) mice developed erythrocytosis/polycythemia through translational derepression of Hif2α, suggesting that IRP1 could be a therapeutic target to treat Chuvash polycythemia. Here, we fed VhlR200W mice supplemented with Tempol, a small, stable nitroxide molecule and observed that Tempol decreased erythropoietin production, corrected splenomegaly, normalized hematocrit levels, and increased the lifespans of these mice. We attribute the reversal of erythrocytosis/polycythemia to translational repression of Hif2α expression by Tempol-mediated increases in the IRE-binding activity of Irp1, as reversal of polycythemia was abrogated in VhlR200W mice in which Irp1 was genetically ablated. Thus, a new approach to the treatment of patients with Chuvash polycythemia may include dietary supplementation of Tempol, which decreased Hif2α expression and markedly reduced life-threatening erythrocytosis/polycythemia in the VhlR200W mice.
Topics: Animals; Basic Helix-Loop-Helix Transcription Factors; Cyclic N-Oxides; Gene Expression Regulation; Humans; Iron Regulatory Protein 1; Mice; Mice, Mutant Strains; Polycythemia; Protein Biosynthesis; Spin Labels
PubMed: 29480820
DOI: 10.1172/JCI97684 -
Haematologica Apr 2018Primary familial and congenital polycythemia is characterized by erythropoietin hypersensitivity of erythroid progenitors due to germline nonsense or frameshift...
Primary familial and congenital polycythemia is characterized by erythropoietin hypersensitivity of erythroid progenitors due to germline nonsense or frameshift mutations in the erythropoietin receptor gene. All mutations so far described lead to the truncation of the C-terminal receptor sequence that contains negative regulatory domains. Their removal is presented as sufficient to cause the erythropoietin hypersensitivity phenotype. Here we provide evidence for a new mechanism whereby the presence of novel sequences generated by frameshift mutations is required for the phenotype rather than just extensive truncation resulting from nonsense mutations. We show that the erythropoietin hypersensitivity induced by a new erythropoietin receptor mutant, p.Gln434Profs*11, could not be explained by the loss of negative signaling and of the internalization domains, but rather by the appearance of a new C-terminal tail. The latter, by increasing erythropoietin receptor dimerization, stability and cell-surface localization, causes pre-activation of erythropoietin receptor and JAK2, constitutive signaling and hypersensitivity to erythropoietin. Similar results were obtained with another mutant, p.Pro438Metfs*6, which shares the same last five amino acid residues (MDTVP) with erythropoietin receptor p.Gln434Profs*11, confirming the involvement of the new peptide sequence in the erythropoietin hypersensitivity phenotype. These results suggest a new mechanism that might be common to erythropoietin receptor frameshift mutations. In summary, we show that primary familial and congenital polycythemia is more complex than expected since distinct mechanisms are involved in the erythropoietin hypersensitivity phenotype, according to the type of erythropoietin receptor mutation.
Topics: Amino Acid Sequence; Animals; Cell Line; Erythropoietin; Germ-Line Mutation; Humans; Mice; Mutant Proteins; Polycythemia; Protein Multimerization; Protein Stability; Receptors, Erythropoietin
PubMed: 29269524
DOI: 10.3324/haematol.2017.176370 -
CMAJ Open 2022Molecular testing for mutations is part of the standard diagnostic workup for patients with suspected polycythemia vera. We sought to characterize evolving practice... (Review)
Review
BACKGROUND
Molecular testing for mutations is part of the standard diagnostic workup for patients with suspected polycythemia vera. We sought to characterize evolving practice patterns in the investigation of erythrocytosis and the prevalence of secondary causes, including use of medications such as sodium-glucose cotransporter-2 (SGLT2) inhibitors, among patients who underwent molecular testing.
METHODS
We reviewed charts of all consecutive patients investigated for erythrocytosis (hemoglobin > 160 g/L for women, > 165 g/L for men) with testing between 2015 and 2021 at London Health Sciences Centre, a tertiary referral centre in Ontario, Canada, to assess changes in rates of mutation positivity, average hemoglobin levels and the prevalence of secondary causes of erythrocytosis.
RESULTS
A total of 891 patients with erythrocytosis underwent mutation testing with an increase in number of tests (particularly from 2017 to 2018), a decrease in the rate of positivity and similar average hemoglobin levels over the study period. We observed a high proportion of patients with secondary causes of erythrocytosis, ranging from 59% to 74% over the study period, including medications associated with erythrocytosis, namely testosterone (6%-11%) and SGLT2 inhibitors (2%-19%). Stopping SGLT2 inhibitors was associated with a significant decrease in hemoglobin levels (mean -14.7 g/L, 95% confidence interval -18.9 to -10.5 g/L) compared with continuation.
INTERPRETATION
Use of SGLT2 inhibitors may be a common and underrecognized secondary cause of elevated hemoglobin levels in patients investigated for erythrocytosis. Our findings underscore the importance of a detailed medical history to support judicious use of molecular testing, in adherence with the current guideline on the investigation of erythrocytosis.
Topics: Male; Humans; Female; Polycythemia Vera; Polycythemia; Ontario; Sodium-Glucose Transporter 2 Inhibitors; Molecular Diagnostic Techniques; Hemoglobins
PubMed: 36347562
DOI: 10.9778/cmajo.20210322 -
Postgraduate Medical Journal Sep 1996Polycythaemia may complicate or be the presenting feature of a wide variety of different pathologies. Early diagnosis and treatment of primary polycythaemia will... (Review)
Review
Polycythaemia may complicate or be the presenting feature of a wide variety of different pathologies. Early diagnosis and treatment of primary polycythaemia will significantly reduce the morbidity and mortality associated with this condition. Patients with a raised packed cell volume are divided into those with a raised red cell mass (absolute polycythaemia), and those with a red cell mass within their normal range (apparent polycythaemia). A standard investigative approach of an absolute polycythaemia enables patients with primary and secondary polycythaemia to be identified, leaving a group termed idiopathic erythrocytosis. There are a number of physiological situations and pathological events associated with idiopathic erythrocytosis and apparent polycythaemia. Careful follow-up of both groups of these patients is essential to identify possible causative mechanisms.
Topics: DNA Probes; Humans; Polycythemia
PubMed: 8949586
DOI: 10.1136/pgmj.72.851.519 -
American Journal of Hematology Nov 2017
Topics: Adult; Aged; Aged, 80 and over; Female; Follow-Up Studies; Hemorrhage; Humans; Male; Middle Aged; Polycythemia; Retrospective Studies; Thrombosis
PubMed: 28762526
DOI: 10.1002/ajh.24873 -
British Medical Journal Dec 1967
Topics: Chorea; Humans; Polycythemia
PubMed: 6060816
DOI: No ID Found -
The Canadian Veterinary Journal = La... Aug 2021A 13-year-old spayed female mixed breed dog was referred for impaired ambulation, limb tremors, back pain, hypergammaglobulinemia on cellulose acetate electrophoresis,...
A 13-year-old spayed female mixed breed dog was referred for impaired ambulation, limb tremors, back pain, hypergammaglobulinemia on cellulose acetate electrophoresis, and mild proteinuria. Conventional radiology and magnetic resonance imaging (MRI) suggested multifocal neoplastic bone lesions. At the referral examination, lameness and bright red mucous membranes were observed. Severe erythrocytosis, a monoclonal peak in the β-2 globulin detected by capillary zone electrophoresis, severe proteinuria, bone marrow infiltration of plasma cells, and low serum erythropoietin concentrations were reported. The final diagnosis was multiple myeloma associated with severe primary erythrocytosis. This presentation in a dog is interesting because the combination of both disorders is rare in humans and has not been reported in dogs. Key clinical message: Although rare, multiple myeloma and primary erythrocytosis can occur together in dogs.
Topics: Animals; Bone Marrow; Dog Diseases; Dogs; Female; Multiple Myeloma; Polycythemia
PubMed: 34341597
DOI: No ID Found