Antonio Fabron

Early cardiac iron overload in children with transfusion-dependent anemias

Quantitative magnetic resonance imaging (MRI) heart iron assessment has been an important advance in the follow-up of patients with transfusion-dependent anemias.[1][1] Few longitudinal data are available on the natural history of cardiac iron overload.[2][2] We refer this letter to the manuscript

HNA-3 gene frequencies in Brazilians and a new polymerase chain reaction-restriction fragment length polymorphism method for HNA-3a/3b genotyping

HNA‐3 antigens are the result of a rs2288904 single‐nucleotide polymorphism (SNP) in the CTL2, and the HNA‐3a and HNA‐3b variants are encoded by a guanine and adenine at Nucleotide Position 461. Anti‐HNA‐3 are involved in severe transfusion‐related acute lung injury reactions and in neonatal alloimmune neutropenia. Since the distribution of the HNA‐3 system was unknown in South Americans, in this study we determined the frequency of the HNA‐3 alleles in Brazilians.

A PCR-Based Strategy for Dombrock Screening in Brazilian Blood Donors Reveals a Novel Allele: The DO{*}A-WL

Background: Determination of the molecular basis underlying the antigens in the Dombrock blood group system has shown various rearrangements between the alleles associated with DO*A and DO*B. Based on this, we employed a PCR‐based strategy to screen DO alleles (DO*A, DO*B, HY*1, HY*2 and JO) in Brazilians. Methods: We tested DNA of 278 Brazilian blood donors by PCR‐RFLP on plates of 96 wells to determine the 793A/G (DO*A/DO*B), 323G/T (HY), 350C/T (JO) and 898C/G (HY*1/HY*2) single nucletide polymorphisms. In order to confirm the results sequence analysis was also performed. Results: When samples of these donors were analyzed, a novel allele combination, the DO*A allele (793A and 323G) associated with 898G was identified and designated as DO*A‐WL allele. This new allele encoding 300Val is the same as HY*1 at nucleotide 898 on the molecular background of DO*A. Among the 556 alleles analyzed by PCR‐RFLP, 3 were DO*A‐WL and 78 were DO*B‐WL. This represents an overall frequency of 0.5% for DO*A‐WL and 14% for DO*B‐WL across the population studied. Conclusion: Molecular screening of Brazilians revealed one novel allele, the DO*A‐WL. Our data highlight the importance of testing a cohort of different populations to determine DO haplotypes and to establish reliable genotyping tests for predicting Doa/Dob status. J. Clin. Lab. Anal. 25:79–82, 2011.

Terapia quelante oral com deferiprona em pacientes com sobrecarga de ferro

Despite the introduction of the parenteral iron chelator desferrioxamine more than 30 years ago, 50% of patients with thalassemia major die before the age of 35 years, predominantly due to iron-induced heart failure. Although desferrioxamine can reduce or stabilize the iron load, many patients still do not receive adequate chelation mainly due to its cumbersome mode of administration which impairs the compliance with the regime of repeatedly subcutaneous infusions. For these patients, the orally active iron chelator deferiprone is an attractive alternative to control the overloaded iron. It has been estimated that more than six thousands patients have already been treated with deferiprone, with some of them taking the chelator for 10 years or more. The deferiprone-induced iron excretion is directly related to the dose of deferiprone and the patients iron load. In most of transfusion-dependent patients, a dose of 75 mg/kg/day is sufficient to offset the transfusional iron-load. Recently, it has been demonstrated that desferrioxamine and deferiprone exhibit different chelating capabilities for the removal of iron from the various body iron pools and that the use of both chelators promote an additive or synergistic iron excretion with rapid reduction in the body iron load. It now is possible to consider tailor-made chelation regimens based on individual patient needs.

Aplicação clínica de filtros leucocitários

A presenca de leucocitos nos produtos hemoterapicos alogenicos transfundidos tem sido associada a ocorrencia de determinadas reacoes transfusionais, tais como a reacao transfusional febril nao-hemolitica, a aloimunizacao e refratariedade a transfusao de plaquetas, a doenca enxerto-versus-hospedeiro, e a efeitos imunomodulatorios. Alem disso, os leucocitos podem ser vetores de transmissao de agentes infecciosos, tais como o CMV, o HTLV-I/II e o EBV. Tem sido postulado que a remocao dos leucocitos em hemocomponentes mediante uso de filtros leucocitarios pode prevenir a ocorrencia dessas reacoes. Entretanto, a eficacia clinica da desleucotizacao permanece sem definicao. Tem sido sugerido que a remocao de 1 log10 de leucocitos previne a reacao transfusional nao-hemolitica, a remocao de 2 log10 pode prevenir a transmissao de viroses, enquanto que a remocao de³ 3 log10 pode ser necessaria para a prevencao de aloimunizacao plaquetaria. Entretanto, devido a carencia de estudos que analisem apropriadamente as vantagens do uso clinico rotineiro dos filtros, permanecem sem completa definicao quais sao as reais indicacoes clinicas para o uso de hemocomponentes desleucotizados; quais sao os graus de desleucotizacao necessarios para prevenir as diferentes reacoes; e se a remocao dos leucocitos deve ser realizada antes ou apos o armazenamento do hemocomponente. Dessa maneira, somente estudos clinicos prospectivos poderao definir o custo-beneficio da aplicacao clinica de filtros leucocitarios em hemoterapia.Leukocytes present in allogeneic blood components have been associated with adverse effects to the recipient. These include the development of febrile transfusion reactions, alloimmunization to human leukocyte antigens, graft-versus-host disease, and immunomodulatory effects. In addition, such leukocytes may be the vector of infectious agents such as CMV, HTLV-I/II, and EBV. It has been postulated that the use of white blood cell filters to reduce the leukocyte content in allogeneic blood products may minimize the occurrence of these biological adverse effects associated with leukocytes present in transfused blood products. However, it is still to be determined the clinical effectiveness of leukodepletion. It has been suggested that 1 log10 leukocyte reduction prevents febrile non-hemolytic transfusion reactions; that a 2 log10 reduction may prevent the transmission of viruses; and that a > or = 3 log10 reduction may be necessary to prevent platelet alloimmunization. However, because there are no data available as guidelines for the use of leukodepleted blood products for most clinical indications, the use of white cell filters should be restricted to selected patients for whom such data exist. Properly designed prospective clinical trials are necessary to provide data to help to define the cost-benefit of the clinical application of leukodepletion.Leukocytes present in allogeneic blood components have been associated with adverse effects to the recipient. These include the development of febrile transfusion reactions, alloimmunization to human leukocyte antigens, graft-versus-host disease, and immunomodulatory effects. In addition, such leukocytes may be the vector of infectious agents such as CMV, HTLV-I/II, and EBV. It has been postulated that the use of white blood cell filters to reduce the leukocyte content in allogeneic blood products may minimize the occurrence of these biological adverse effects associated with leukocytes present in transfused blood products. However, it is still to be determined the clinical effectiveness of leukodepletion. It has been suggested that 1 log10 leukocyte reduction prevents febrile non-hemolytic transfusion reactions; that a 2 log10 reduction may prevent the transmission of viroses; and that a³ 3 log10 reduction may be necessary to prevent platelet alloimmunization. However, because there are no data available as guidelines for the use of leukodepleted blood products for most clinical indications, the use of white cell filters should be restricted to selected patients for whom such data exist. Properly designed prospective clinical trials are necessary to provide data to help to define the cost-benefit of the clinical application of leukodepletion.

576 Hla and Chronic Urticaria with Positive Autologous Serum Skin Test among Brazilians

Background Many autoimmune diseases are associated with certain alleles of the human leukocyte antigen (HLA) system, and recent studies have shown that, in many cases, chronic urticaria has autoimmune etiology. An association between class I and II alleles of the major histocompatibility complex (MHC) and idiopathic chronic urticaria (ICU) has previously been observed in different populations, but there are still no studies on Brazilian populations in this respect. The involvement of MHC classes I and II (loci A, B and DR) in Brazilian patients with ICU and a positive autologous serum skin test (ASST) was investigated and compared with a healthy population group. Methods DNA was extracted from the blood of 42 patients with ICU (28 women; mean age ± SD: 44 ± 12 years; range: 19 to 88 years) and MHC classes I and II alleles were determined using the polymerase chain reaction (PCR) and a laboratory test for oligonucleotide hybridization using a single-filament probe. The frequencies of these alleles in patients with chronic urticaria were compared with the frequencies in 1000 genetically unrelated voluntary blood donors from the same region of Brazil. The diagnosis of idiopathic chronic urticaria was based on the patients’ clinical histories and routine laboratory tests. Only the patients with positive ASSTs were selected. The allele distribution results from the patient and control groups were analyzed using odds ratios and 95% confidence intervals. Results No statistically significant differences were found between the ASST-positive patients with chronic urticaria and the control group, in relation to the MHC classes I and II alleles studied. Conclusions We found that in this population group, there was no specific association between the HLA alleles studied (HLA-A, HLA-B and DRB1) and ASST-positive chronic urticaria. We believe that further population studies are needed in order to investigate the possible existence of this association.