BackgroundRed cell distribution width (RDW), a classical parameter used in the differential diagnosis of anemia, has recently been recognized as a marker of chronic inflammation and high levels of oxidative stress (OS). Fanconi anemia (FA) is a genetic disorder associated to redox imbalance and dysfunctional response to OS. Clinically, it is characterized by progressive bone marrow failure, which remains the primary cause of morbidity and mortality. Macrocytosis and increased fetal hemoglobin, two indicators of bone marrow stress erythropoiesis, are generally the first hematological manifestations to appear in FA. However, the significance of RDW and its possible relation to stress erythropoiesis have never been explored in FA. In the present study we analyzed routine complete blood counts from 34 FA patients and evaluated RDW, correlating with the hematological parameters most consistently associated with the FA phenotype.ResultsWe showed, for the first time, that RDW is significantly increased in FA. We also showed that increased RDW is correlated with thrombocytopenia, neutropenia and, most importantly, highly correlated with anemia. Analyzing sequential hemograms from 3 FA patients with different clinical outcomes, during 10 years follow-up, we confirmed a consistent association between increased RDW and decreased hemoglobin, which supports the postulated importance of RDW in the evaluation of hematological disease progression.ConclusionsThis study shows, for the first time, that RDW is significantly increased in FA, and this increment is correlated with neutropenia, thrombocytopenia, and highly correlated with anemia. According to the present results, it is suggested that increased RDW can be a novel marker of stress erythropoiesis in FA.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-016-0485-0) contains supplementary material, which is available to authorized users.
Glucose-6-phosphate isomerase (GPI) deficiency cause hereditary nonspherocytic hemolytic anemia (HNSHA) of variable severity in individuals homozygous or compound heterozygous for mutations in GPI gene. This work presents clinical features and genotypic results of two patients of Portuguese origin with GPI deficiency. The patients suffer from a mild hemolytic anemia (Hb levels ranging from 10 to 12.7g/mL) associated with macrocytosis, reticulocytosis, hyperbilirubinemia, hyperferritinemia and slight splenomegaly. Genomic DNA sequencing revealed in one patient homozygosity for a new missense mutation in exon 3, c.260G>C (p.Gly87Ala), and in the second patient compound heterozygosity for the same missense mutation (p.Gly87Ala), along with a frameshift mutation resulting from a single nucleotide deletion in exon 14, c.1238delA (p.Gln413Arg fs*24). Mutation p.Gln413Arg fs*24 is the first frameshift null mutation to be described in GPI deficiency. Molecular modeling suggests that the structural change induced by the p.Gly87Ala pathogenic variant has direct impact in the structural arrangement of the region close to the active site of the enzyme.
ResumenA telangiectasia hemorrágica hereditária (THH) é uma doença autossómi-ca dominante, caracterizada por telangiectasias mucocutâneas e viscerais, envolvendo vários órgãos com malformações vasculares. Apresentamos o caso de um paciente com THH e anemia grave por deficiência de ferro, dependente de transfusões de sangue a cada 3 semanas, apesar da terapêutica com ferro endovenoso. Iniciou terapêutica hormonal com estradiol, sem resposta hematológica satisfatória, pelo que começou tratamento com talidomida 200 mg/dia, com melhoria evidente, sem necessidade de transfusões adicionais, mesmo após redução da dose para 100 mg/dia. Apesar do tratamento prolongado, não acorreram efeitos colaterais.Palabras clave: Telangiectasia hemorrágica hereditaria. Anemia. Talidomida. AbstractHereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease that is characterized by mucocutaneous and visceral telangiectasia, involving several organs with vascular malformations. We present a patient with HHT and severe iron deficiency anemia, requiring blood transfusions every 3 weeks, despite treatment with intravenous iron. There was no satisfactory haematological response after hormone therapy with estradiol, so we started treatment with thalidomide 200 mg / day, with dramatic improvement, with no need for transfusions, even after dose reduction to 100 mg / day. Despite the long treatment with thalidomide, side effects did not occurred.Keywords: Hereditary hemorrhagic telangiectasia. Anemia. Thalidomide. IntroduçãoA telangiectasia hemorrágica hereditária (THH) ou síndrome de Rendu-Osler-Weber é uma doença hereditária, autossó-mica dominante, com uma prevalência variável 1 . A THH é caracterizada por telangiectasias que podem envolver a pele e as mucosas, mas também o cérebro (10%-15%), pulmão (5%-30%), tracto gastrointestinal (15%-30%) e fígado (até 70%) 1,2 . Pode apresentar-se como malformações arteriovenosas (MAV) ou como múltiplas telangiectasias difusas 3 .A THH classifica-se em 2 tipos, sendo a tipo 2 a mais frequente. É causada por mutações em genes que codificam proteínas transmembranares envolvidas na via de sinalização do factor de crescimento de transformação (TGF)-β e são predominantemente expressas no endotélio vascular 2 . Na THH tipo 1, ocorre uma mutação no gene da endoglina no cromossoma 9q344 e na THH tipo 2, ocorre uma mutação no gene da cinase do receptor-like da ativina (ALK)-1, no cromossoma 12q135. O diagnóstico clínico de THH baseia-se na presença de pelo menos três das quatro principais características clínicas (critérios de Curaçau): epistáxis, telangiectasias cutâneas ou mucosas, envolvimento visceral e história familiar de THH 1 .Apresentamos um caso de um paciente com THH grave, com anemia sideropénica dependente de transfusões, tratado com talidomida de forma extremamente eficaz. Relato de casoPaciente do sexo masculino, de 66 anos de idade, enviado para a consulta de Hematologia Clínica em Novembro de 2008 por anemia grave (hemoglobina 6.7 g/dL). Apresentava epistáxis frequentes, negando...
Summary:Hemorrhagic cystitis (HC) is a common complication following hemopoietic stem cell transplantation (HSCT), its incidence ranging from 7 to 52% of all patients. Late occurring HC frequently results from viral infections. We describe a patient who developed severe polyomavirus-associated HC, which responded dramatically to a single dose of intra-muscular vidarabine. Previous studies show an improvement in HC with vidarabine therapy, but to date only the intravenous route of administration has been described and responses described take from several days to weeks. This report confirms the safety and efficacy of vidarabine administered intramuscularly when used in patients with an adequate platelet count, thereby making its use feasible when intravenous vidarabine is not available. Bone Marrow Transplantation (2000) 26, 1229-1230. Keywords: hemorrhagic cystitis; vidarabine; intra-muscular; transplantation Hemorrhagic cystitis (HC) is a common complication following hemopoietic stem cell transplantation (HSCT), its incidence ranging from 7 to 52% of all patients. 1,2 Early onset HC is associated with high-dose cyclophosphamide conditioning regimens and is prevented by the widespread use of the acrolein chelator mesna, hyperhydration or continuous bladder irrigation, while late occurring HC frequently results from viral infections (eg BK virus, adenovirus type 11). [3][4][5] BKV is a ubiquitous virus which infects more than 60% of the population worldwide at an early age. 6 Antibodies to BKV are demonstrated in the serum of 80 to 100% of adult patients before transplant. Since post-transplantation viruria only occurs in patients who were seropositive pre- transplantation, reactivation, probably associated with immune deficiency, is postulated to be the likely cause. 7 The purine analogue vidarabine (adenine arabinoside) has been shown to have in vitro antiviral activity against human polyomavirus by selectively inhibiting viral DNA polymerase. Successful treatment of polyomavirus-associated HC occurring after HSCT with disappearance or reduction in viruria has already been reported using intravenous vidarabine. 8 We describe a patient who developed severe polyomavirus-associated HC and who responded dramatically to a single dose of intra-muscular vidarabine, thereby demonstrating the efficacy and safety of this drug when employed intramuscularly. Case reportA 13-year-old boy was diagnosed with severe aplastic anemia and underwent allogeneic peripheral blood stem cell transplantation from an HLA-identical brother. After conditioning with cyclophosphamide (50 mg/kg for 3 days with mesna 50 mg/kg 0, 4 and 8 h after cyclophosphamide) and anti-thymocyte globulin (30 mg/kg for 3 days), 8.3 × 10 6 CD34 + cells/kg were infused. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporin A at 1.5 mg/kg/12 h from day −4 onwards and methotrexate without folinic rescue on days +1, 3, 6 and 11.More than 500 granulocytes/mm 3 and 20 × 10 9 platelets/l were achieved on days +14 and +12, respectively. Complete chime...
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