RESUMO
Idiopathic erythrocytosis (IE) is characterized by an increase of red blood cell mass without an identified cause. Its diagnosis is based on the exclusion of polycythemia vera (PV), secondary acquired polycythemias and various congenital primary and secondary polycythemias. The frequency of IE has been estimated to be 1.1 per 1000 subjects, which is higher than that observed in PV. Heterogeneous mechanisms underlying IE have been suggested, including 'early' PV and unrecognized secondary or congenital polycythemia. However, the transition of a patient initially classified as IE into PV is a rare occurrence, when more sophisticated diagnostic techniques are employed. IE is a stable disease with a low thrombotic risk and a low, if any, tendency to spontaneous progression to acute leukemia or myelofibrosis. Phlebotomy in patients with IE is controversial. Myelosuppressive drugs should be avoided since their use is associated with evolution into acute leukemia in about 10% of patients.
Assuntos
Policitemia , Humanos , Policitemia/diagnóstico , Policitemia/etiologiaRESUMO
Mutations leading to red cell enzyme deficiencies can be associated with diverse phenotypes that range from hemolytic anemia, methemoglobinemia, polycythemia, and neurological and developmental abnormalities. While most of these mutations occur sporadically, some such as common glucose-6-phosphate dehydrogenase (G6PD) mutants are endemic and rarely cause disease. Common G6PD mutants likely reached their prevalence because they provide some protection against severe malarial complications. In this review G6PD, pyruvate kinase, 5' nucleotidase, and cytochrome b5 reductase deficiencies will be discussed in greater detail. Limitations of commonly used screening tests for detection of these disorders will also be emphasized, as well as emerging knowledge about non-enzymatic function of the glycolytic enzymes.
Assuntos
Anemia Hemolítica/enzimologia , Eritrócitos/enzimologia , Deficiência de Glucosefosfato Desidrogenase/genética , Metemoglobinemia/enzimologia , Policitemia/enzimologia , 5'-Nucleotidase/sangue , 5'-Nucleotidase/deficiência , 5'-Nucleotidase/genética , Anemia Hemolítica/sangue , Anemia Hemolítica/genética , Citocromo-B(5) Redutase/sangue , Citocromo-B(5) Redutase/deficiência , Citocromo-B(5) Redutase/genética , Variação Genética , Glucosefosfato Desidrogenase/sangue , Glucosefosfato Desidrogenase/genética , Deficiência de Glucosefosfato Desidrogenase/sangue , Deficiência de Glucosefosfato Desidrogenase/complicações , Glicólise , Humanos , Malária/complicações , Metemoglobina/genética , Metemoglobinemia/sangue , Metemoglobinemia/genética , Policitemia/sangue , Policitemia/genética , Piruvato Quinase/sangue , Piruvato Quinase/deficiência , Piruvato Quinase/genéticaRESUMO
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 , Etnicidade/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-LindauRESUMO
We describe a woman with severe neutropenia and dependency on red blood cell transfusions who had previously undergone Billroth II surgery and whose bone marrow (BM) showed morphologic characteristics typical of myelodysplastic syndrome (MDS) with ringed sideroblasts. She had transient reversal of anemia and severe neutropenia after therapy with erythropoietin and granulocyte colony-stimulating factor. Because of relapse while receiving growth factors, the patient was referred for allogeneic BM transplantation. A pretransplantation nutritional evaluation revealed severe copper deficiency, and her hematologic abnormalities resolved fully with copper therapy. This case shows that copper deficiency should be an integral part of the differential diagnosis of sideroblastic MDS, even in patients not requiring parenteral nutrition.
