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1.
Cancer ; 125(8): 1258-1266, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30644531

RESUMO

BACKGROUND: Somatic mutations in hypoxia-inducible factor 2α (HIF2A) are associated with polycythemia-paraganglioma syndrome. Specifically, the classic presentation of female patients with recurrent paragangliomas (PGLs), polycythemia (at birth or in early childhood), and duodenal somatostatinomas has been described. Studies have demonstrated that somatic HIF2A mutations occur as postzygotic events and some to be associated with somatic mosaicism affecting hematopoietic and other tissue precursors. This phenomenon could explain the development of early onset of polycythemia in the absence of erythropoietin-secreting tumors. METHODS: Correlation analysis was performed between mosaicism of HIF2A mutant patients and clinical presentations. RESULTS: Somatic HIF2A mutations (p.A530V, p.P531S, and p.D539N) were identified in DNA extracted from PGLs of 3 patients. No somatic mosaicism was detected through deep sequencing of blood genomic DNA. Compared with classic syndrome, both polycythemia and PGL in all 3 patients developed at an advanced age with polycythemia at age 30, 30, and 17 years and PGLs at age 34, 30, and 55 years, respectively. Somatostatinomas were not detected, and 2 patients had ophthalmic findings. The biochemical phenotype in all 3 patients was noradrenergic with 18 F-fluorodopa PET/CT as the most sensitive imaging modality. All patients demonstrated multiplicity, and none developed metastatic disease. CONCLUSION: These findings suggest that newer techniques need to be developed to detect somatic mosaicism in patients with this syndrome. Absence of HIF2A mosaicism in patients with somatic HIF2A mutations supports association with late onset of the disease, milder clinical phenotype, and an improved prognosis compared with patients who have HIF2A mosaicism.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Paraganglioma/classificação , Mutação Puntual , Policitemia/classificação , Adolescente , Adulto , Idade de Início , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Pessoa de Meia-Idade , Mosaicismo , Paraganglioma/diagnóstico por imagem , Paraganglioma/genética , Policitemia/diagnóstico por imagem , Policitemia/genética , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Análise de Sequência de DNA
2.
Blood ; 132(5): 469-483, 2018 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-29891534

RESUMO

Chuvash polycythemia is an autosomal recessive form of erythrocytosis associated with a homozygous p.Arg200Trp mutation in the von Hippel-Lindau (VHL) gene. Since this discovery, additional VHL mutations have been identified in patients with congenital erythrocytosis, in a homozygous or compound-heterozygous state. VHL is a major tumor suppressor gene, mutations in which were first described in patients presenting with VHL disease, which is characterized by the development of highly vascularized tumors. Here, we identify a new VHL cryptic exon (termed E1') deep in intron 1 that is naturally expressed in many tissues. More importantly, we identify mutations in E1' in 7 families with erythrocytosis (1 homozygous case and 6 compound-heterozygous cases with a mutation in E1' in addition to a mutation in VHL coding sequences) and in 1 large family with typical VHL disease but without any alteration in the other VHL exons. In this study, we show that the mutations induced a dysregulation of VHL splicing with excessive retention of E1' and were associated with a downregulation of VHL protein expression. In addition, we demonstrate a pathogenic role for synonymous mutations in VHL exon 2 that altered splicing through E2-skipping in 5 families with erythrocytosis or VHL disease. In all the studied cases, the mutations differentially affected splicing, correlating with phenotype severity. This study demonstrates that cryptic exon retention and exon skipping are new VHL alterations and reveals a novel complex splicing regulation of the VHL gene. These findings open new avenues for diagnosis and research regarding the VHL-related hypoxia-signaling pathway.


Assuntos
Éxons , Predisposição Genética para Doença , Mutação , Policitemia/genética , Processamento de RNA , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Doença de von Hippel-Lindau/genética , Adolescente , Adulto , Criança , Feminino , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Policitemia/classificação , Policitemia/patologia , Adulto Jovem , Doença de von Hippel-Lindau/patologia
4.
Rev. cuba. inform. méd ; 8(supl.1)2016.
Artigo em Espanhol | LILACS, CUMED | ID: biblio-844909

RESUMO

Se realiza un estudio del desempeño de los modelos ocultos de Márkov (HMM) en la clasificación morfológica supervisada de eritrocitos en muestras de sangre periférica de pacientes con anemia drepanocítica. Los contornos se representan de forma novedosa considerando las diferencias angulares en la curvatura de los puntos del mismo. El entrenamiento de cada modelo se realiza tanto con la descripción normal de los contornos como con la representación de la rotación de los mismos, para garantizar una mayor estabilidad en los parámetros estimados. Se desarrolla un proceso de validación cruzada de 5x1 para estimación del error. Se obtienen las medidas de sensibilidad, precisión y especificidad de la clasificación. Los mejores resultados en cuanto a sensibilidad se obtienen al clasificar eritrocitos pertenecientes a dos clases: normales (96 por ciento) y elongados (99 por ciento). Al considerar además una clase de eritrocitos con otras deformaciones los mejores resultados se obtienen realizando el entrenamiento de los modelos con la rotación de todos los contornos, que alcanzó sensibilidades de normales (94 por ciento), elongados (82 por ciento) y con otras deformaciones (76 por ciento)(AU)


A study of the performance of Hidden Markov Models (HMM) in morphologic supervised classification of erythrocytes in peripheral blood smears of patients with sickle cell disease is realized. Contours are represented in original way considering the angular differences in the curvature of the points of the same. The training of every model comes true with the normal description of the contours and with the representation of the rotation of the same, in order to guarantee a bigger stability in the esteemed parameters. A process of validation crossed of 5x1 for estimate of the error is developed. The measures of sensibility, precision and specificity of classification are obtained. The best results obtain when classifying erythrocytes in two classes, with sensibility values in normal of 96 percent and elongated 99 percent. In the classification of erythrocytes considering the class of other deformations better results obtain accomplishing the training of the models with the rotation of all the contours, that it attained sensibilities of normal (94 percent), elongated (82 percent) and with other deformations (76 percent)(AU)


Assuntos
Humanos , Policitemia/classificação , Aplicações da Informática Médica , Design de Software , Cadeias de Markov , Técnicas de Laboratório Clínico/métodos , Doenças Hematológicas/sangue
5.
Curr Hematol Malig Rep ; 8(4): 333-41, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24146204

RESUMO

Although the revised World Health Organization (WHO) criteria for the diagnosis and classification of myeloproliferative neoplasms (MPN) were defined by a panel of expert hematopathologists and clinicians, controversy has been repeatedly expressed questioning the clinical usefulness and reproducibility of these diagnostic guidelines. In particular, the distinction between essential thrombocythemia (ET), early/prefibrotic primary myelofibrosis (PMF) and initial stages of polycythemia vera (PV) is still a matter of debate. In this context, it has been argued that clinical correlations with histological features were not firmly substantiated. On the other hand, recently published data from independently performed studies have repeatedly validated the reproducibility of the WHO criteria and provided persuasive evidence that discrimination of early/prefibrotic PMF has a significant impact on the risk of myelofibrotic and leukemic transformation. However, as has been explicitly required, the WHO concept is based on the recognition of characteristic bone marrow patterns and a consensus of clinical and molecular data.


Assuntos
Policitemia/classificação , Mielofibrose Primária/classificação , Trombocitemia Essencial/classificação , Diagnóstico Diferencial , Neoplasias Hematológicas/diagnóstico , Humanos , Policitemia/diagnóstico , Mielofibrose Primária/diagnóstico , Reprodutibilidade dos Testes , Trombocitemia Essencial/diagnóstico , Organização Mundial da Saúde
6.
Pediatr Blood Cancer ; 60(11): 1734-8, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23776154

RESUMO

During recent years, the increasing knowledge of genetic and physiological changes in polycythemia vera (PV) and of different types of congenital erythrocytosis has led to fundamental changes in recommendations for the diagnostic approach to patients with erythrocytosis. Although widely accepted for adult patients this approach may not be appropriate with regard to children and adolescents affected by erythrocytosis. The "congenital erythrocytosis" working group established within the framework of the MPN&MPNr-EuroNet (COST action BM0902) addressed this question in a consensus finding process and developed a specific algorithm for the diagnosis of erythrocytosis in childhood and adolescence which is presented here.


Assuntos
Algoritmos , Policitemia/classificação , Policitemia/diagnóstico , Adolescente , Adulto , Criança , Humanos
8.
Artigo em Inglês | MEDLINE | ID: mdl-20008248

RESUMO

Erythrocytosis results when there is an increased red cell mass and thus an increased hemoglobin. The causes can be divided into primary intrinsic defects of the erythroid progenitor cell and secondary defects, where factors external to the erythroid compartment are responsible. Both can then be further divided into congenital and acquired categories. Congenital causes include mutations of the erythropoietin receptor and defects of the oxygen-sensing pathway including VHL, PHD2 and HIF2A mutations. When fully investigated there remain a number of patients in whom no cause can be elucidated who are currently described as having idiopathic erythrocytosis. Investigation should start with a full history and examination. Having eliminated the common entity polycythemia vera, further direction for investigation is guided by the erythropoietin level. Clinical consequences of the various erythrocytoses are not clear, but in some groups thromboembolic events have been described in young patients. Evidence is lacking to define best management, but aspirin and venesection to a target hematocrit should be considered.


Assuntos
Policitemia/epidemiologia , Adulto , Aspirina/uso terapêutico , Viscosidade Sanguínea , Diagnóstico Diferencial , Eritropoese , Eritropoetina/deficiência , Eritropoetina/metabolismo , Eritropoetina/farmacologia , Feminino , Hematócrito , Humanos , Hipóxia/sangue , Hipóxia/genética , Hipóxia/fisiopatologia , Masculino , Mutação , Flebotomia , Inibidores da Agregação de Plaquetas/uso terapêutico , Policitemia/classificação , Policitemia/congênito , Policitemia/diagnóstico , Policitemia/tratamento farmacológico , Policitemia/terapia , Policitemia Vera/diagnóstico , Receptores da Eritropoetina/genética , Transdução de Sinais , Trombofilia/tratamento farmacológico , Trombofilia/etiologia
9.
Int J Lab Hematol ; 30(6): 447-59, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18823397

RESUMO

An absolute erythrocytosis is present when the red cell mass is raised and the haematocrit is elevated above prescribed limits. Causes of an absolute erythrocytosis can be primary where there is an intrinsic problem in the bone marrow and secondary where there an event outside the bone marrow driving erythropoiesis. This can further be divided into congenital and acquired causes. There remain an unexplained group idiopathic erythrocytosis. Investigation commencing with thorough history taking and examination and then investigation depending on initial features is required. Clear simple criteria for polycythaemia vera are now defined. Those who do not fulfil these criteria require further investigation depending on the clinical scenario and initial results. The erythropoietin level provides some guidance as to the direction in which to proceed and the order and extent of investigation necessary in an individual patient. It should thus be possible to make an accurate diagnosis in the majority of patients.


Assuntos
Policitemia Vera/classificação , Policitemia Vera/diagnóstico , Policitemia/classificação , Policitemia/diagnóstico , Volume de Eritrócitos/fisiologia , Eritropoetina/sangue , Hematócrito , Hemoglobinas , Humanos , Hipóxia/sangue , Mutação , Policitemia/etiologia , Policitemia/genética , Policitemia Vera/etiologia , Policitemia Vera/genética
11.
Blood ; 111(4): 1862-5, 2008 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-18029552

RESUMO

Various clinical prognostic scoring systems (PSSs) have been suggested as means of selecting high-risk chronic idiopathic myelofibrosis (CIMF) patients at diagnosis. The WHO has recently proposed strict diagnostic criteria for CIMF, and the European consensus for bone marrow fibrosis (BMF) grading recommends 4 classes. It has been suggested that BMF grading may play a prognostic role in CIMF, but it has never been compared with the other PSSs in the same patients. We tested a prognostic model for overall survival (OS) based on the WHO criteria and BMF grading in 113 consecutive patients with chronic myeloproliferative disorders (98 with CIMF and 15 with postpolycythemic myelofibrosis), and compared the findings with those of PSSs. The results showed that our model is significantly associated with different OSs and, unlike the other PSSs, clearly discriminates the OS of intermediate- and high-risk patients.


Assuntos
Medula Óssea/patologia , Mielofibrose Primária/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Contagem de Células Sanguíneas , Doença Crônica , Europa (Continente) , Feminino , Hemoglobinas/metabolismo , Humanos , Masculino , Metaplasia/patologia , Pessoa de Meia-Idade , Policitemia/classificação , Policitemia/patologia , Mielofibrose Primária/sangue , Mielofibrose Primária/classificação , Prognóstico
13.
Curr Hematol Rep ; 4(3): 238-42, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15865879

RESUMO

This review will focus on the molecular basis of certain polycythemic disorders. Primary polycythemias are characterized by acquired somatic or inherited germ-line mutations expressed within hematopoietic progenitors that cause increased accumulation of red blood cells. Polycythemia vera (PV), an acquired condition, is the most common primary polycythemia; although some progress has been made in the understanding of PV, its molecular basis remains unknown. In contrast, recent advances in delineating the molecular defects of some inherited polycythemias have greatly furthered our knowledge of the regulation of erythropoiesis and hypoxia sensing; however, more work needs to be done.


Assuntos
Policitemia Vera/genética , Policitemia/genética , Adulto , Animais , Criança , Estudos de Coortes , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/fisiologia , Modelos Animais de Doenças , Eritropoese/genética , Eritropoetina/fisiologia , Grupos Étnicos/genética , Feminino , Efeito Fundador , Proteínas Ligadas por GPI , Mutação em Linhagem Germinativa , Humanos , Hipóxia/fisiopatologia , Fator 1 Induzível por Hipóxia , Subunidade alfa do Fator 1 Induzível por Hipóxia , Isoantígenos , Janus Quinase 2 , Masculino , Glicoproteínas de Membrana , Camundongos , Proteínas Nucleares/genética , Proteínas Nucleares/fisiologia , Policitemia/classificação , Policitemia/congênito , Policitemia/etnologia , Policitemia/metabolismo , Policitemia Vera/diagnóstico , Policitemia Vera/metabolismo , Complexo de Endopeptidases do Proteassoma/fisiologia , Processamento de Proteína Pós-Traducional , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Receptores de Superfície Celular/genética , Receptores da Eritropoetina/genética , Receptores da Eritropoetina/fisiologia , Federação Russa/epidemiologia , Fatores de Transcrição/genética , Fatores de Transcrição/fisiologia , Proteínas Supressoras de Tumor/deficiência , Proteínas Supressoras de Tumor/genética , Ubiquitina/metabolismo , Ubiquitina-Proteína Ligases/deficiência , Ubiquitina-Proteína Ligases/genética , Proteína Supressora de Tumor Von Hippel-Lindau
14.
Ann Hematol ; 84(3): 137-45, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15599750

RESUMO

Polycythemias or erythrocytoses in childhood and adolescence are very rare. Systematic data on the clinical presentation and laboratory evaluations as well as on treatment regimens are sparse. The diagnostic program in absolute erythrocytosis includes extensive clinical, hematological, biochemical, and molecular biological examinations which should be applied following a stepwise algorithm. Absolute erythrocytoses are usually subdivided into primary and secondary forms. Primary erythrocytosis is a condition in which the erythropoietic compartment is expanding independently of extrinsic influences or by responding inadequately to them. Primary erythrocytoses include primary familial and congenital polycythemia (PFCP) due to mutations of the erythropoietin (Epo) receptor gene and the myeloproliferative disorder polycythemia vera. Secondary erythrocytoses are driven by hormonal factors (predominantly by Epo) extrinsic to the erythroid compartment. The increased Epo secretion may represent either a physiologic response to tissue hypoxia, an abnormal autonomous Epo production, or a dysregulation of the oxygen-dependent Epo synthesis. Congenital secondary erythrocytoses are caused, e.g., by hemoglobin variants with increased oxygen affinity, by 2,3-bisphosphoglycerate deficiency, or by mutations in the von Hippel-Lindau gene associated with a disturbed oxygen-dependent regulation of Epo synthesis.


Assuntos
Policitemia , Algoritmos , Criança , Técnicas de Laboratório Clínico , Predisposição Genética para Doença , Humanos , Policitemia/classificação , Policitemia/diagnóstico , Policitemia/etiologia , Policitemia/terapia
15.
Hematol Oncol Clin North Am ; 17(5): 1151-8, vi, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-14560779

RESUMO

In this article, polycythemic disorders are classified based on the current understanding of biology of erythropoieses and divided into primary and secondary polycythemias. Special emphasis is given to recently uncovered molecular bases of newly described congenital polycythemic disorders. This clarification of the pathophysiology of some of the congenital polycythemic states has obvious utility for more accurate diagnosis and rational prognostic determination. The molecular basis of congenital thrombocytoses is only beginning to be uncovered. In contrast, the molecular bases of polycythemia vera and essential thrombocythemia remain unknown, thus their diagnostic criteria are imprecise and their treatment remains largely empirical. The central premise of this article is that deciphering the molecular basis of human diseases leads to improved understanding of hematopoiesis, precise diagnosis, and the potential for development of a specific therapy.


Assuntos
Policitemia/classificação , Policitemia/genética , Trombocitose/classificação , Trombocitose/genética , Humanos , Nefropatias/genética , Hepatopatias/genética , Mutação
16.
Am J Hum Genet ; 73(2): 412-9, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12844285

RESUMO

The von Hippel-Lindau (pVHL) protein plays an important role in hypoxia sensing. It binds to the hydroxylated hypoxia-inducible factor 1 alpha (HIF-1 alpha) and serves as a recognition component of an E3-ubiquitin ligase complex. In hypoxia or secondary to a mutated VHL gene, the nondegraded HIF-1 alpha forms a heterodimer with HIF-beta and leads to increased transcription of hypoxia-inducible genes, including erythropoietin (EPO). The autosomal dominant cancer-predisposition von Hippel-Lindau (VHL) syndrome is due to inheritance of a single mutated allele of VHL. In contrast, we recently showed that homozygous germline 598C-->T VHL mutation leads to Chuvash polycythemia (CP). We subsequently found VHL mutations in three unrelated individuals unaffected with CP, one of whom was compound heterozygous for the 598C-->T mutation and another VHL mutation. We now report seven additional polycythemic patients with VHL mutations in both alleles. Two Danish siblings and another American boy were homozygous for the VHL 598C-->T mutation. Three unrelated white Americans were compound heterozygotes for 598C-->T and another VHL mutation, 562C-->G in two and 574C-->T in the third. Additionally, a Croatian boy was homozygous for a 571C-->G VHL mutation, the first example of homozygous VHL germline mutation causing polycythemia, other than the VHL 598C-->T mutation. We have not observed VHL syndrome-associated tumors in polycythemic subjects or their heterozygous relatives; however, this will need to be evaluated by longitudinal studies. Over all, we found that up to half of the consecutive patients with apparent congenital polycythemia and increased serum Epo we have examined have mutations of both VHL alleles. Those findings, along with reports of CP, underscore that VHL mutations are the most frequent cause of congenital polycythemia and define a new class of polycythemic disorder, polycythemias due to augmented hypoxia sensing.


Assuntos
Genes Supressores de Tumor , Ligases/genética , Mutação , Policitemia/congênito , Policitemia/genética , Proteínas Supressoras de Tumor , Ubiquitina-Proteína Ligases , Adolescente , Adulto , Alelos , Sequência de Bases , Criança , DNA/genética , Análise Mutacional de DNA , Feminino , Heterozigoto , Homozigoto , Humanos , Hipóxia/genética , Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia , Ligases/química , Ligases/metabolismo , Substâncias Macromoleculares , Masculino , Modelos Moleculares , Linhagem , Policitemia/classificação , Policitemia/metabolismo , Fatores de Transcrição/química , Fatores de Transcrição/metabolismo , Proteína Supressora de Tumor Von Hippel-Lindau
19.
Pathol Biol (Paris) ; 49(2): 170-7, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11317965

RESUMO

By definition, idiopathic erythrocytosis (IE) applies to a group of patients characterised by having a measured RCM above their predicted normal range (an absolute erythrocytosis) and following investigation do not have a form of primary or secondary erythrocytosis. Patients with IE are heterogenous. The possibilities include physiological variation, 'early' polycythaemia vera (10-15% develop clear features of PV over a few years), unrecognized congenital erythrocytosis, unrecognized or unrecognizable secondary acquired erythrocytosis or a currently undescribed form of primary or secondary erythrocytosis. Patients are more commonly male with a median age at presentation of 55-60 years. Approximately half of the patients present with vascular occlusive complications. Retrospective evidence indicates that vascular occlusion occurs less frequently when the PCV is controlled at normal levels. Venesection is the treatment of choice to lower the PCV. As a general approach to management, all patients with a PCV above 0.54 should be venesected to a PCV less than 0.45. This target PCV should also apply to patients with lesser degrees of raised PCV who have additional other risk factors for vascular occlusion.


Assuntos
Policitemia , Idoso , Arteriopatias Oclusivas/etiologia , Medula Óssea/patologia , Clorambucila/efeitos adversos , Clorambucila/uso terapêutico , Diagnóstico Diferencial , Doenças do Sistema Endócrino/complicações , Volume de Eritrócitos , Células Precursoras Eritroides/patologia , Eritropoetina/sangue , Predisposição Genética para Doença , Humanos , Hipóxia/complicações , Nefropatias/complicações , Leucemia/induzido quimicamente , Leucemia Induzida por Radiação/etiologia , Pessoa de Meia-Idade , Radioisótopos de Fósforo/efeitos adversos , Radioisótopos de Fósforo/uso terapêutico , Policitemia/classificação , Policitemia/congênito , Policitemia/diagnóstico , Policitemia/etiologia , Policitemia/terapia , Policitemia Vera/diagnóstico , Receptores da Eritropoetina/deficiência , Receptores da Eritropoetina/genética , Deleção de Sequência , Fumar/sangue , Acidente Vascular Cerebral/etiologia
20.
Semin Hematol ; 38(1 Suppl 2): 21-4, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11242598

RESUMO

There is no single diagnostic marker for the only known type of primary acquired erythrocytosis, polycythemia vera (PV). The Polycythemia Vera Study Group (PVSG) used a combination of major and minor diagnostic criteria. However, these guidelines have some limitations and in the presence of newer diagnostic tools, have been re-evaluated. The recommendations of the Radionuclide Panel of the International Council for Standardization Hematology based on surface area are recommended over red blood cell mass (RCM) mL/kg expressions. Absolute erythrocytosis can be assumed in males and females with packed cell volume (PCV) values greater than 0.60 and greater than 0.56, respectively. A satisfactory strategy of investigation for a secondary erythrocytosis must be used. Hypoxemia, as well as renal and hepatic pathology, must be excluded. In unexplained absolute erythrocytoses, pO(2)(50) values and serum erythropoietin (EPO) levels should be examined. The latter can be disappointing in the confirmation of a secondary erythrocytosis, but elevated values contraindicate a diagnosis of a primary erythrocytosis. Establishment of a clonal marrow population supports a diagnosis of PV. Thus an acquired karyotypic abnormality is a major criterion. Palpable splenomegaly remains an important diagnostic marker. Scanning techniques to demonstrate splenic enlargement should be used with caution. Allowance must be made for interobserver and intraobserver differences and variation in normal spleen size with age and size of the subject. Splenomegaly demonstrated in this way should be taken as a minor criterion. An increased neutrophil count (>10 x 10(9)/L and >12.5 x 10(9)/L in smokers) is readily measurable and should replace total white blood cell count. The error in measurement of neutrophil alkaline phosphatase (NAP) score is large, making it an unsuitable diagnostic criterion. Neutrophil and platelet counts (>400 x 10(9)/L) should be taken as separate minor criteria. Endogenous erythroid colonies (EEC) grown from the peripheral blood have been used as a marker of PV, but it is an expensive technique that is not standardized and not totally specific for PV. Low serum EPO values found in the majority of patients with PV should hold a linked minor criterion position with EEC. Expert opinions should be obtained if bone marrow histology is to be used in the diagnosis of PV, but histology holds an important role in confirming the diagnosis. Semin Hematol 38(suppl 2):21-24.


Assuntos
Policitemia Vera/diagnóstico , Diagnóstico Diferencial , Humanos , Policitemia/classificação , Guias de Prática Clínica como Assunto
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