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1.
Hematology ; 26(1): 881-884, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34753407

RESUMO

Mean corpuscular volume (MCV) as a measure of the size of red blood cells (RBCs) has been pivotal in the diagnosis and morphologic classification of anemias for over a century. Despite its ubiquitous use and time-honored diagnostic value, one essential attribute of MCV has remained under the radar. It has been long underappreciated that the size of RBC correlates with the amount of hemoglobin (Hb) that it accommodates and, therefore, is an important determining factor of the total Hb level. By scrutinizing this basic principle, it has become possible to uncover a hitherto obscured relationship between MCV, hematocrit (Hct) and RBCs described as a dynamic equilibrium. This principle is shown to be invaluable in interpreting RBC parameters, particularly for the evaluation of patients with polycythemia.


Assuntos
Eritrócitos/patologia , Hematócrito , Policitemia/patologia , Idoso , Contagem de Eritrócitos , Índices de Eritrócitos , Feminino , Hemoglobinas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Policitemia/sangue
2.
J Assoc Physicians India ; 69(9): 11-12, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34585896

RESUMO

A 73-year-old hypertensive was found to have new-onset polycythemia during his routine health check up. A workup revealed no evidence of polycythemia rubra vera or a secondary cause of his polycythemia (his erythropoietin level was normal, he had no splenomegaly, and a test for JAK2 v617F mutation was negative). Over the next year of follow up, his hematological profile returned to normal levels. We conclude that this patient had Gaisbock's syndrome, a relative polycythemia that occurs when there is clinically evident contraction of the intravascular fluid space (plasma volume) in smokers and people who received diuretics.


Assuntos
Hipertensão , Policitemia Vera , Policitemia , Idoso , Humanos , Masculino , Policitemia/etiologia , Policitemia Vera/complicações , Policitemia Vera/diagnóstico
3.
Am J Case Rep ; 22: e932252, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34491978

RESUMO

BACKGROUND Osimertinib is an oral third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) approved as first-line therapy for advanced non-small cell lung cancer (NSCLC) with positive EGFR mutation. Rashes, nail toxicity, and diarrhea are common adverse events. Hematological adverse effects, including anemia, thrombocytopenia, and lymphocytopenia, have been reported. However, erythrocytosis has not been reported as an adverse event. To the best of our knowledge, we report the first case of acute lower extremity thrombosis presumably caused by osimertinib-induced erythrocytosis. CASE REPORT A 70-year-old man with epidermal EGFR-mutant advanced NSCLC presented with acute left sural pain. The patient's left foot was cold, and peripheral arterial Doppler signals were absent. He had developed erythrocytosis of unknown etiology during osimertinib therapy. Hemoglobin (Hb) and hematocrit were 22.6 g/dL and 62.5%, respectively. Contrast-enhanced computed tomography showed thrombotic occlusion of the popliteal artery. Other than erythrocytosis, there was no possible cause of arterial thrombosis. Osimertinib was discontinued immediately because the NSCLC started to resist treatment and was presumed to be the cause of erythrocytosis. He received endovascular treatment (EVT). Following serial EVT and debridement, his fourth toe was amputated for necrosis. Erythrocytosis persisted 8 months during osimertinib therapy. Hb levels decreased to 15.4 mg/dL due to blood loss complicated with catheter thrombectomy and remained normal for 20 months after osimertinib discontinuation. The patient died of cancer progression. CONCLUSIONS This case suggests the erythrocytosis was possibly caused by osimertinib. We may need to monitor Hb levels during osimertinib therapy and be alert to thrombosis once Hb starts to rise.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Policitemia , Trombose , Acrilamidas , Idoso , Compostos de Anilina , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Extremidade Inferior , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Mutação , Policitemia/induzido quimicamente , Inibidores de Proteínas Quinases/efeitos adversos
5.
Can Vet J ; 62(8): 849-853, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34341597

RESUMO

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 ß-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.


Assuntos
Doenças do Cão , Mieloma Múltiplo , Policitemia , Animais , Medula Óssea , Doenças do Cão/diagnóstico , Cães , Feminino , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/veterinária , Policitemia/diagnóstico , Policitemia/veterinária
6.
Am J Physiol Regul Integr Comp Physiol ; 321(3): R504-R512, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34346722

RESUMO

The high-altitude maladaptation syndrome known as chronic mountain sickness (CMS) is characterized by polycythemia and is associated with proteinuria despite unaltered glomerular filtration rate. However, it remains unclear if indigenous highlanders with CMS have altered volume regulatory hormones. We assessed NH2-terminal pro-B-type natriuretic peptide (NT pro-BNP), plasma aldosterone concentration, plasma renin activity, kidney function (urinary microalbumin, glomerular filtration rate), blood volume, and estimated pulmonary artery systolic pressure (ePASP) in Andean males without (n = 14; age = 39 ± 11 yr) and with (n = 10; age = 40 ± 12 yr) CMS at 4,330 m (Cerro de Pasco, Peru). Plasma renin activity (non-CMS: 15.8 ± 7.9 ng/mL vs. CMS: 8.7 ± 5.4 ng/mL; P = 0.025) and plasma aldosterone concentration (non-CMS: 77.5 ± 35.5 pg/mL vs. CMS: 54.2 ± 28.9 pg/mL; P = 0.018) were lower in highlanders with CMS compared with non-CMS, whereas NT pro-BNP was not different between groups (non-CMS: 1394.9 ± 214.3 pg/mL vs. CMS: 1451.1 ± 327.8 pg/mL; P = 0.15). Highlanders had similar total blood volume (non-CMS: 90 ± 15 mL·kg-1 vs. CMS: 103 ± 18 mL·kg-1; P = 0.071), but Andeans with CMS had greater total red blood cell volume (non-CMS: 46 ± 10 mL·kg-1 vs. CMS: 66 ± 14 mL·kg-1; P < 0.01) and smaller plasma volume (non-CMS: 43 ± 7 mL·kg-1 vs. CMS: 35 ± 5 mL·kg-1; P = 0.03) compared with non-CMS. There were no differences in ePASP between groups (non-CMS: 32 ± 9 mmHg vs. CMS: 31 ± 8 mmHg; P = 0.6). A negative correlation was found between plasma renin activity and glomerular filtration rate in both groups (group: r = -0.66; P < 0.01; non-CMS: r = -0.60; P = 0.022; CMS: r = -0.63; P = 0.049). A smaller plasma volume in Andeans with CMS may indicate an additional CMS maladaptation to high altitude, causing potentially greater polycythemia and clinical symptoms.


Assuntos
Aclimatação , Doença da Altitude/fisiopatologia , Altitude , Volume Sanguíneo , Policitemia/fisiopatologia , Adulto , Albuminúria/etiologia , Albuminúria/fisiopatologia , Aldosterona/sangue , Doença da Altitude/sangue , Doença da Altitude/diagnóstico , Doença da Altitude/etiologia , Pressão Arterial , Biomarcadores/sangue , Doença Crônica , Taxa de Filtração Glomerular , Humanos , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Policitemia/sangue , Policitemia/diagnóstico , Policitemia/etiologia , Artéria Pulmonar/fisiopatologia , Renina/sangue
7.
Am J Physiol Heart Circ Physiol ; 321(4): H738-H747, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34448634

RESUMO

Hemoconcentration can influence hypoxic pulmonary vasoconstriction (HPV) via increased frictional force and vasoactive signaling from erythrocytes, but whether the balance of these mechanism is modified by the duration of hypoxia remains to be determined. We performed three sequential studies: 1) at sea level, in normoxia and isocapnic hypoxia with and without isovolumic hemodilution (n = 10, aged 29 ± 7 yr); 2) at altitude (6 ± 2 days acclimatization at 5,050 m), before and during hypervolumic hemodilution (n = 11, aged 27 ± 5 yr) with room air and additional hypoxia [fraction of inspired oxygen ([Formula: see text])= 0.15]; and 3) at altitude (4,340 m) in Andean high-altitude natives with excessive erythrocytosis (EE; n = 6, aged 39 ± 17 yr), before and during isovolumic hemodilution with room air and hyperoxia (end-tidal Po2 = 100 mmHg). At sea level, hemodilution mildly increased pulmonary artery systolic pressure (PASP; +1.6 ± 1.5 mmHg, P = 0.01) and pulmonary vascular resistance (PVR; +0.7 ± 0.8 wu, P = 0.04). In contrast, after acclimation to 5,050 m, hemodilution did not significantly alter PASP (22.7 ± 5.2 vs. 24.5 ± 5.2 mmHg, P = 0.14) or PVR (2.2 ± 0.9 vs. 2.3 ± 1.2 wu, P = 0.77), although both remained sensitive to additional acute hypoxia. In Andeans with EE at 4,340 m, hemodilution lowered PVR in room air (2.9 ± 0.9 vs. 2.3 ± 0.8 wu, P = 0.03), but PASP remained unchanged (31.3 ± 6.7 vs. 30.9 ± 6.9 mmHg, P = 0.80) due to an increase in cardiac output. Collectively, our series of studies reveal that HPV is modified by the duration of exposure and the prevailing hematocrit level. In application, these findings emphasize the importance of accounting for hematocrit and duration of exposure when interpreting the pulmonary vascular responses to hypoxemia.NEW & NOTEWORTHY Red blood cell concentration influences the pulmonary vasculature via direct frictional force and vasoactive signaling, but whether the magnitude of the response is modified with duration of exposure is not known. By assessing the pulmonary vascular response to hemodilution in acute normobaric and prolonged hypobaric hypoxia in lowlanders and lifelong hypobaric hypoxemia in Andean natives, we demonstrated that a reduction in red cell concentration augments the vasoconstrictive effects of hypoxia in lowlanders. In high-altitude natives, hemodilution lowered pulmonary vascular resistance, but a compensatory increase in cardiac output following hemodilution rendered PASP unchanged.


Assuntos
Aclimatação , Altitude , Pressão Arterial , Eritrócitos/metabolismo , Hemodiluição , Hipóxia/sangue , Policitemia/sangue , Artéria Pulmonar/fisiopatologia , Vasoconstrição , Adulto , Viscosidade Sanguínea , Débito Cardíaco , Frequência Cardíaca , Hematócrito , Humanos , Hipóxia/diagnóstico , Hipóxia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Policitemia/diagnóstico , Policitemia/fisiopatologia , Fatores de Tempo , Resistência Vascular , Adulto Jovem
8.
Sci Rep ; 11(1): 15898, 2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-34354145

RESUMO

The YPEL family genes are highly conserved across a diverse range of eukaryotic organisms and thus potentially involved in essential cellular processes. Ypel4, one of five YPEL family gene orthologs in mouse and human, is highly and specifically expressed in late terminal erythroid differentiation (TED). In this study, we investigated the role of Ypel4 in murine erythropoiesis, providing for the first time an in-depth description of a Ypel4-null phenotype in vivo. We demonstrated that the Ypel4-null mice displayed a secondary polycythemia with macro- and reticulocytosis. While lack of Ypel4 did not affect steady-state TED in the bone marrow or spleen, the anemia-recovering capacity of Ypel4-null cells was diminished. Furthermore, Ypel4-null red blood cells (RBC) were cleared from the circulation at an increased rate, demonstrating an intrinsic defect of RBCs. Scanning electron micrographs revealed an ovalocytic morphology of Ypel4-null RBCs and functional testing confirmed reduced deformability. Even though Band 3 protein levels were shown to be reduced in Ypel4-null RBC membranes, we could not find support for a physical interaction between YPEL4 and the Band 3 protein. In conclusion, our findings provide crucial insights into the role of Ypel4 in preserving normal red cell membrane integrity.


Assuntos
Proteínas de Transporte/genética , Membrana Eritrocítica/fisiologia , Eritropoese/genética , Anemia/metabolismo , Animais , Proteína 1 de Troca de Ânion do Eritrócito/metabolismo , Proteínas de Transporte/metabolismo , Membrana Eritrocítica/genética , Eritrócitos/metabolismo , Eritrócitos Anormais/metabolismo , Eritropoese/fisiologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Policitemia/genética , Baço
11.
Probl Endokrinol (Mosk) ; 67(3): 37-44, 2021 06 13.
Artigo em Russo | MEDLINE | ID: mdl-34297500

RESUMO

Functioning gonadotroph adenomas are rare pituitary tumors secreting one or two gonadotropins (follicle-stimulating hormone (FSH) and/or luteinizing hormone (LH)), which are hormonally active. In the majority of cases, gonadotroph tumors are endocrinologically "silent" and make up more than a half of non-functioning pituitary adenomas. In this article we describe a rare clinical case of LH/FSH-secreting pituitary macroadenoma with bitemporal hemianopsia in a 62-year-old man. The patient underwent transnasal transsphenoidal adenomectomy, leading to remission. The distinctive feature of this case is the presence of secondary erythrocytosis due to endogenous hyperandrogenism, which required several blood exfusions to normaliza the level of hematocrit before surgery. It is noteworthy that clinical signs of erythrocytosis were present long before visual impairment. This clinical case demonstrates difficulties in the early diagnosis of functioning gonadotroph adenomas.


Assuntos
Adenoma , Gonadotrofos , Neoplasias Hipofisárias , Policitemia , Adenoma/complicações , Idoso , Hormônio Foliculoestimulante , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/complicações , Policitemia/diagnóstico
12.
BMC Pulm Med ; 21(1): 235, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34261472

RESUMO

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.


Assuntos
Fumar Cigarros/efeitos adversos , Policitemia/epidemiologia , Policitemia/etiologia , Doença Pulmonar Obstrutiva Crônica/complicações , Idoso , Idoso de 80 Anos ou mais , Monóxido de Carbono/sangue , Estudos Transversais , Feminino , Humanos , Hipóxia/complicações , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Oxigenoterapia/métodos , Prevalência , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/terapia , Enfisema Pulmonar/diagnóstico por imagem , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Espirometria , Tomografia Computadorizada por Raios X , Estados Unidos/epidemiologia
15.
J Physiol ; 599(17): 4021-4044, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34245004

RESUMO

KEY POINTS: Humans suffering from polycythaemia undergo multiple circulatory adaptations including changes in blood rheology and structural and functional vascular adaptations to maintain normal blood pressure and vascular shear stresses, despite high blood viscosity. During exercise, several circulatory adaptations are observed, especially involving adrenergic and non-adrenergic mechanisms within non-active and active skeletal muscle to maintain exercise capacity, which is not observed in animal models. Despite profound circulatory stress, i.e. polycythaemia, several adaptations can occur to maintain exercise capacity, therefore making early identification of the disease difficult without overt symptomology. Pharmacological treatment of the background heightened sympathetic activity may impair the adaptive sympathetic response needed to match local oxygen delivery to active skeletal muscle oxygen demand and therefore inadvertently impair exercise capacity. ABSTRACT: Excessive haematocrit and blood viscosity can increase blood pressure, cardiac work and reduce aerobic capacity. However, past clinical investigations have demonstrated that certain human high-altitude populations suffering from excessive erythrocytosis, Andeans with chronic mountain sickness, appear to have phenotypically adapted to life with polycythaemia, as their exercise capacity is comparable to healthy Andeans and even with sea-level inhabitants residing at high altitude. By studying this unique population, which has adapted through natural selection, this study aimed to describe how humans can adapt to life with polycythaemia. Experimental studies included Andeans with (n = 19) and without (n = 17) chronic mountain sickness, documenting exercise capacity and characterizing the transport of oxygen through blood rheology, including haemoglobin mass, blood and plasma volume and blood viscosity, cardiac output, blood pressure and changes in total and local vascular resistances through pharmacological dissection of α-adrenergic signalling pathways within non-active and active skeletal muscle. At rest, Andeans with chronic mountain sickness had a substantial plasma volume contraction, which alongside a higher red blood cell volume, caused an increase in blood viscosity yet similar total blood volume. Moreover, both morphological and functional alterations in the periphery normalized vascular shear stress and blood pressure despite high sympathetic nerve activity. During exercise, blood pressure, cardiac work and global oxygen delivery increased similar to healthy Andeans but were sustained by modifications in both non-active and active skeletal muscle vascular function. These findings highlight widespread physiological adaptations that can occur in response to polycythaemia, which allow the maintenance of exercise capacity.


Assuntos
Doença da Altitude , Policitemia , Aclimatação , Altitude , Animais , Humanos , Fenótipo
16.
J Vet Intern Med ; 35(4): 1977-1980, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34110655

RESUMO

Primary erythrocytosis (PE) is a rare myeloproliferative neoplasm in cats resulting in the overproduction of erythrocytes. Current treatment modalities include repeated phlebotomy and chemotherapeutic drugs. These treatments may not be well tolerated by the cat and can present safety and financial challenges to owners. Because of the rarity of PE, prospective studies for new treatment options are difficult to perform. This case report describes the novel use of onion powder in an attempt to produce Heinz body-induced erythrocyte destruction in order to decrease total erythrocyte mass and normalize the hematocrit in a cat with PE. To our knowledge, the use of onion powder in the treatment of PE in cats has never been described before and may have potential as a safe, low-cost, and highly accessible alternative treatment for this rare disease.


Assuntos
Doenças do Gato , Policitemia , Animais , Medula Óssea , Doenças do Gato/tratamento farmacológico , Gatos , Cebolas , Policitemia/tratamento farmacológico , Policitemia/veterinária , Pós , Estudos Prospectivos
17.
BMJ Case Rep ; 14(6)2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34162611

RESUMO

Polycythemia vera (PV) is an orphan haematological disease and one of the most common myeloproliferative diseases, with the incidence rate of about 0.4-2.8 cases per 100 000 population per year. In patients, proliferation of all three haematopoietic lineages is observed, typically with the development of erythrocytosis. As a rule, PV occurs in patients aged 60-70 years, slightly more often in men. The main clinical signs of PV are weakness, significant burning sensation in fingers and palms due to the increased blood viscosity and microcirculation disorders, discomfort in the left hypochondrium due to splenomegaly at the background of extramedullary haematopoietic sites development, as well as gross vascular complications (thrombosis) of various localisation. Our clinical case represents a rare cardiac manifestation of the PV in a young man.


Assuntos
Hipertensão , Transtornos Mieloproliferativos , Policitemia Vera , Policitemia , Humanos , Hipertensão/etiologia , Janus Quinase 2 , Masculino , Policitemia/etiologia , Policitemia Vera/complicações , Policitemia Vera/diagnóstico
18.
Blood Adv ; 5(12): 2563-2568, 2021 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-34129019

RESUMO

TEMPI syndrome (telangiectasias, elevated erythropoietin level and erythrocytosis, monoclonal gammopathy, perinephric fluid collections, and intrapulmonary shunting) is a newly defined multisystemic disease with its pathophysiology largely unknown. Here, we report the whole-genome sequencing (WGS) analysis on the tumor-normal paired cells from a patient with TEMPI syndrome. WGS revealed somatic nonsynonymous single-nucleotide variants, including SLC7A8, NRP2, and AQP7. Complex structural variants of chromosome 2 were found, particularly within regions where some putative oncogenes reside. Of potential clinical relevance, duplication of 22q11.23 was identified, and the expression of the located gene macrophage migration inhibitory factor (MIF) was significantly upregulated in 3 patients with TEMPI syndrome. Importantly, the level of serum MIF in one patient with TEMPI syndrome was significantly decreased in accordance with the downtrend of plasma cells, M-protein, hemoglobin, and erythropoietin and the improvement of telangiectasias, perinephric fluid collections, and intrapulmonary shunting after treatment with plasma cell-directed therapy. In conclusion, our study provides insights into the genomic landscape and suggests a role of MIF in the pathophysiology of TEMPI syndrome.


Assuntos
Fatores Inibidores da Migração de Macrófagos , Gamopatia Monoclonal de Significância Indeterminada , Paraproteinemias , Policitemia , Telangiectasia , Humanos , Oxirredutases Intramoleculares , Fatores Inibidores da Migração de Macrófagos/genética
19.
Ann Hematol ; 100(8): 1965-1973, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34013406

RESUMO

Erythrocytosis has a diverse background. While polycythaemia vera has well defined criteria, the diagnostic approach and management of other types of erythrocytosis are more challenging. The aim of study was to retrospectively analyse the aetiology and management of non-clonal erythrocytosis patients referred to a haematology outpatient clinic in an 8-year period using a 3-step algorithm. The first step was inclusion of patients with Hb > 185 g/L and/or Hct > 0.52 in men and Hb > 165 g/L and/or Hct > 0.48 in women on two visits ≥ two months apart, thus confirming true erythrocytosis. Secondly, polycythaemia vera was excluded and secondary causes of erythrocytosis (SE) identified. Thirdly, idiopathic erythrocytosis patients (IE) were referred to next-generation sequencing for possible genetic background evaluation. Of the 116 patients, 75 (65%) are men and 41 (35%) women, with non-clonal erythrocytosis 34/116 (29%) had SE, 15/116 (13%) IE and 67/116 (58%) stayed incompletely characterized (ICE). Patients with SE were significantly older and had significantly higher Hb and Hct compared to patients with IE. Most frequently, SE was attributed to obstructive sleep apnoea and smoking. Phlebotomies were performed in 56, 53 and 40% of patients in the SE, IE, and ICE group, respectively. Approx. 70% of patients in each group received aspirin. Thrombotic events were registered in 12, 20 and 15% of SE, IE and ICE patients, respectively. Congenital erythrocytosis type 4 (ECYT4) was diagnosed in one patient. The study demonstrates real-life management of non-clonal erythrocytosis which could be optimized using a 3-step diagnostic algorithm.


Assuntos
Policitemia/diagnóstico , Policitemia/terapia , Adulto , Gerenciamento Clínico , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Flebotomia , Policitemia/congênito , Policitemia/genética , Estudos Retrospectivos
20.
Leukemia ; 35(8): 2166-2181, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34021251

RESUMO

JAK2 unmutated or non-polycythemia vera (PV) erythrocytosis encompasses both hereditary and acquired conditions. A systematic diagnostic approach begins with documentation of historical hematocrit (Hct)/hemoglobin (Hgb) measurements and classification of the process as life-long/unknown duration or acquired. Further investigation in both categories is facilitated by determination of serum erythropoietin level (EPO). Workup for hereditary/congenital erythrocytosis requires documentation of family history and laboratory screening for high-oxygen affinity hemoglobin variants, 2, 3 biphosphoglycerate deficiency, and germline mutations that are known to alter cellular oxygen sensing (e.g., PHD2, HIF2A, VHL) or EPO signaling (e.g., EPOR mutations); the latter is uniquely associated with subnormal EPO. Acquired erythrocytosis is often elicited by central or peripheral hypoxia resulting from cardiopulmonary disease/high-altitude dwelling or renal artery stenosis, respectively; EPO in the former instance is often normal (compensated by negative feed-back). Other conditions associated with acquired erythrocytosis include EPO-producing tumors and the use of drugs that promote erythropoiesis (e.g., testosterone, erythropoiesis stimulating agents). "Idiopathic erythrocytosis" loosely refers to an otherwise not explained situation. Historically, management of non-PV erythrocytosis has been conflicted by unfounded concerns regarding thrombosis risk, stemming from limited phenotypic characterization, save for Chuvash polycythemia, well-known for its thrombotic tendency. In general, cytoreductive therapy should be avoided and phlebotomy is seldom warranted where frequency is determined by symptom control rather than Hct threshold. Although not supported by hard evidence, cardiovascular risk optimization and low-dose aspirin use are often advised. Application of modern genetic tests and development of controlled therapeutic intervention trials are needed to advance current clinical practice.


Assuntos
Janus Quinase 2/genética , Mutação , Policitemia/diagnóstico , Policitemia/terapia , Humanos , Policitemia/genética , Prognóstico
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