RESUMO
The decision of November 6th, 2006 defining the principles of best practices recommends that posttransfusional red cell alloantibodies research is performed after one to three months after. In the University hospital of Brest, the haemovigilance unit takes charge of sending the medical prescription within the required time and centralizing the results. We wished to estimate if the realization of this research still remains relevant. METHODS: A prospective analysis was performed in 2015. We evaluated the realization rate, the red cell alloantibodies rate and the recipient adverse reactions with the diagnostic category: alloimmunization (delayed serological transfusion reaction, DSTR). RESULTS: In 2015, 2162 prescriptions were sent to the 3271 transfused patients. One thousand and eighteen red cell alloantibodies research were done, i.e. a return rate of 61%. Among them, 12 alloantibodies appeared (0.9%) within an average of 56 days. Thirty-three other alloantibodies appeared and were discovered most frequently before a new transfusion. In 10 cases, a posttransfusional research was done that was negative. A survey was conducted among GHCOH members to describe the practices in these health institutions. Twelve questionnaires were analysed. Ten institutions performed a posttransfusional alloantibodies research by issuing a prescription at the patient's exit with a return rate between 0.14 and 16%; 1 institution has a centralized organization with a return rate of 68.3%; 1566 red cell alloantibodies research were performed and among them, 24 alloantibodies appeared (1.53%). CONCLUSION: These results indicate that to be effective, the management of this biological test must be centralized. Despite this, the red cell alloantibodies rate remains very low (0.9 and 1.53%) and raises the question of the relevance of this systematic testing after transfusion, which is in any case mandatory before a new transfusion of red blood cells.
Assuntos
Segurança do Sangue/métodos , Transfusão de Sangue/legislação & jurisprudência , Isoanticorpos/sangue , Antígenos de Grupos Sanguíneos/imunologia , Segurança do Sangue/economia , Segurança do Sangue/normas , Custos e Análise de Custo , Membrana Eritrocítica/imunologia , França , Hospitais Universitários , Humanos , Imunização , Isoanticorpos/biossíntese , Isoanticorpos/imunologia , Guias de Prática Clínica como Assunto , Prevalência , Estudos Prospectivos , Inquéritos e Questionários , Fatores de Tempo , Reação Transfusional/epidemiologia , Reação Transfusional/imunologia , Reação Transfusional/prevenção & controleRESUMO
The widespread worldwide implementation of ABO-incompatible kidney transplantation (ABOi KT) programs have increased the chances of gaining access to kidney transplantation. In Italy the practice of ABOi KT has somewhat lagged behind that practiced in many other European Countries. Even though some Italian Transplant Centers have recently started ABOi KT programs, most of them appear still reluctant in adopting this procedure. In this paper, nephrologists from two different Italian Transplant Centers express their contrasting point of view concerning specific issues related to ABOi KT. The first issue concerns the safety and efficacy of ABOi KT and how it compares with HLA-incompatible kidney transplantation. The second concerns to what extent does ABOi KT be adopted, whenever a paired kidney exchange program is available. The third issue regards the indications or contraindications of ABOi KT in specific patient categories. The last issue is about the economical sustainability of ABOi KT programs nowadays. The different point of views of the discussants are summarized in the context of the most recent available evidence.
Assuntos
Incompatibilidade de Grupos Sanguíneos/imunologia , Transplante de Rim , Vírus BK , Contraindicações , Rejeição de Enxerto , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/imunologia , Humanos , Isoanticorpos/biossíntese , Itália , Transplante de Rim/efeitos adversos , Transplante de Rim/economia , Transplante de Rim/normas , Infecções por Polyomavirus/etiologia , Infecções por Polyomavirus/imunologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/imunologia , Risco , Doadores de Tecidos/provisão & distribuição , Obtenção de Tecidos e Órgãos/organização & administração , Obtenção de Tecidos e Órgãos/normas , Resultado do Tratamento , Infecções Tumorais por Vírus/etiologia , Infecções Tumorais por Vírus/imunologiaRESUMO
Besides specific organisational requirements, the transfusional chain in French ultra-marine areas has specificities related to the epidemiology of infectious diseases and to population characteristics. We focus on some of these sociodemographic and medical peculiarities: the challenge of autosufficiency in relation to demographic trends; epidemiologic risks associated to emergent viruses such as dengue and Chikungunya, and the strategies that had been implemented to face last outbreaks; inappropriate selection criteria for eligibility to blood donation (biologic characteristics of Afro-Caribbeans not taken into account for the low hemoglobin deferral threshold; absence of guidelines for the screening of hemoglobinopathies AS/AC, present in 8% of the target population); specific indications for transfusion, such as platelet use in dengue fever or RBC transfusion in sickle cell disease. Due to the high polymorphism of erythrocyte antigens in Afro-Caribbeans, intra-ethnic transfusion facilitates compatibility for common antigens, but is responsible for the emergence of allo-antibodies difficult to identify in the absence of specific antisera or panels; molecular typing of erythrocyte antigens would allow detection of those patients at risk for immunization, expressing variant antigens or lacking high frequency antigens, as well as the characterization of RBC expressing immunogenic so called low frequency antigens. In an era of periodic emergence of new viruses in Europe (dengue, Chikungunya, West Nile virus...) and with the spreading of diseases with high transfusional requirements, such as sickle cell disease, ultra-marine services represent laboratories for the study of future trends and problems in transfusion medicine.
Assuntos
Doadores de Sangue , Transfusão de Sangue , Infecções por Alphavirus/epidemiologia , Infecções por Alphavirus/prevenção & controle , Infecções por Alphavirus/transmissão , Anemia Falciforme/etnologia , Doadores de Sangue/estatística & dados numéricos , Antígenos de Grupos Sanguíneos/genética , Incompatibilidade de Grupos Sanguíneos/etnologia , Incompatibilidade de Grupos Sanguíneos/prevenção & controle , Segurança do Sangue/normas , Transfusão de Sangue/estatística & dados numéricos , Patógenos Transmitidos pelo Sangue , Febre de Chikungunya , Surtos de Doenças , Seleção do Doador , Etnicidade/genética , França , Hemoglobinopatias/etnologia , Hemoglobinopatias/terapia , Humanos , Isoanticorpos/biossíntese , Malária/epidemiologia , Malária/prevenção & controle , Malária/transmissão , Reunião , Fatores Socioeconômicos , Índias OcidentaisRESUMO
In high-income countries, the large availability of coagulation factors for replacement therapy of patients with hemophilia A has raised the life expectancy of these lifelong bleeders to that of males from the general population. The practicing clinician is offered a multitude of choices among several commercial brands of factor VIII extracted from human plasma or engineered from mammalian cell cultures by means of recombinant DNA technology. This article has the goal to offer our opinions on how to choose among the different products, that we consider interchangeable relevant to their clinical efficacy in the control of bleeding and safety from pathogen transmission. Hence, the main determinants of our choices are price and the risk of occurrence of factor VIII inhibitory alloantibodies. With this as background, we present the rationale underlying the choices for different categories of patients with severe hemophilia A: previously untreated patients, multiply treated patients, and patients undergoing immune tolerance induction with large doses of factor VIII to eradicate inhibitors. Mention is also made to the possible strategies that should be implemented to make available coagulation factors for replacement therapy in developing countries.
Assuntos
Fator VIII/uso terapêutico , Hemofilia A/tratamento farmacológico , Animais , Patógenos Transmitidos pelo Sangue , Linhagem Celular , Criança , Pré-Escolar , Países Desenvolvidos , Países em Desenvolvimento , Contaminação de Medicamentos , Custos de Medicamentos , Fator VIII/efeitos adversos , Fator VIII/economia , Fator VIII/genética , Fator VIII/imunologia , Fator VIII/isolamento & purificação , Hemofilia A/economia , Humanos , Tolerância Imunológica , Lactente , Reembolso de Seguro de Saúde , Isoanticorpos/biossíntese , Itália , Masculino , Seleção de Pacientes , Ensaios Clínicos Controlados Aleatórios como Assunto , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/economia , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/uso terapêutico , Especificidade da EspécieRESUMO
After the patents of biopharmaceuticals have expired, based on specific regulatory approval pathways copied products ("biosimilars" or "follow-on biologics") have been launched in the EU. This article summarizes experiences with hematopoietic medicines, namely the epoetins (two biosimilars traded under five different brand names) and the filgrastims (two biosimilars, six brand names). Physicians and pharmacists should be familiar with the legal and pharmacological specialities of biosimilars: The production process can differ from that of the original, clinical indications can be extrapolated, glycoproteins contain varying isoforms, the formulation may differ from the original, and biopharmaceuticals are potentially immunogenic. Only on proof of quality, efficacy and safety, biosimilars are a viable option because of their lower costs.
Assuntos
Produtos Biológicos/uso terapêutico , Eritropoetina/uso terapêutico , Anemia/etiologia , Anemia/terapia , Antineoplásicos/efeitos adversos , Produtos Biológicos/economia , Produtos Biológicos/farmacocinética , Produtos Biológicos/normas , Doença Crônica , Uso de Medicamentos , Eritropoetina/economia , Eritropoetina/imunologia , Eritropoetina/farmacocinética , União Europeia , Filgrastim , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Guias como Assunto , Humanos , Isoanticorpos/biossíntese , Nefropatias/sangue , Nefropatias/complicações , Legislação de Medicamentos , Marketing , Neoplasias/sangue , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Patentes como Assunto , Polietilenoglicóis , Controle de Qualidade , Proteínas Recombinantes/economia , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/farmacocinética , Proteínas Recombinantes/uso terapêutico , Aplasia Pura de Série Vermelha/etiologia , Equivalência Terapêutica , Organização Mundial da SaúdeAssuntos
Ensaio de Imunoadsorção Enzimática , Interferon Tipo I/imunologia , Isoanticorpos/biossíntese , Esclerose Múltipla/imunologia , Reações Antígeno-Anticorpo , Monitoramento de Medicamentos , Ensaio de Imunoadsorção Enzimática/economia , Ensaio de Imunoadsorção Enzimática/estatística & dados numéricos , Humanos , Fatores Imunológicos/imunologia , Fatores Imunológicos/uso terapêutico , Interferon Tipo I/uso terapêutico , Isoanticorpos/imunologia , Esclerose Múltipla/terapia , Testes de Neutralização , Valor Preditivo dos Testes , Proteínas RecombinantesRESUMO
Factor VIII (FVIII) inhibitor antibodies are produced in a proportion of hemophilia A patients. Development of anti-FVIII inhibitor antibodies is a T cell-dependent response, mediated by FVIII specific CD4(+) T cells. This study was performed to investigate the contribution of T helper (Th) cell-mediated cytokine response in inhibitor production. Peripheral blood mononuclear cells (PBMCs) were obtained from hemophilia A patients with (n = 14) or without inhibitor (n = 14) and from normal individuals (n = 14). Following stimulation of PBMCs with rFVIII and phytohemagglutinin (PHA) mitogen, the secreted cytokines, interferon-gamma (IFN-gamma), interleukin-10 (IL-10), and transforming growth factor-beta1 (TGF-beta1), in culture supernatant and the proliferative response were assessed using sandwich ELISA and (3)H-thymidine incorporation, respectively. No significant proliferative response to FVIII was observed, whereas PHA induced a strong response in all groups. No cytokine secretion was observed in response to FVIII stimulation. Although PHA induced IL-10, TGF-beta1 and IFN-gamma secretion in all groups, the level of IFN-gamma was significantly lower in hemophilia A patients than in normal individuals (p < 0.0001). The levels of TGF-beta1 and IL-10 were similarly higher in patients compared with normal subjects, but the difference was not statistically significant. Lack of FVIII-induced proliferative response and cytokine production together with reduced secretion of PHA-induced IFN-gamma in both groups of patients suggest involvement of nonspecific immunosuppression possibly due to hepatitis C virus (HCV) infection observed in the majority of patients.
Assuntos
Citocinas/biossíntese , Fator VIII/imunologia , Hemofilia A/metabolismo , Isoanticorpos/biossíntese , Isoanticorpos/sangue , Adolescente , Adulto , Animais , Células Cultivadas , Criança , Citocinas/metabolismo , Fator VIII/antagonistas & inibidores , Fator VIII/fisiologia , Feminino , Hemofilia A/sangue , Hemofilia A/imunologia , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Masculino , Camundongos , Pessoa de Meia-Idade , Mitógenos/farmacologia , Fito-Hemaglutininas/farmacologiaAssuntos
Hemofilia B/terapia , Animais , Células CHO , Análise Custo-Benefício , Cricetinae , Cricetulus , Contaminação de Medicamentos , Fator IX/imunologia , Fator IX/isolamento & purificação , Fator IX/uso terapêutico , Hemofilia B/economia , Hemofilia B/imunologia , Humanos , Isoanticorpos/biossíntese , Protrombina/imunologia , Protrombina/isolamento & purificação , Protrombina/uso terapêutico , Proteínas Recombinantes de Fusão/imunologia , Proteínas Recombinantes de Fusão/uso terapêutico , Trombose/induzido quimicamente , Transfecção , Viroses/transmissãoRESUMO
Mouse hearts transplanted into MHC disparate donors are usually rejected 1 week after placement. It is widely accepted that alloantigen-reactive helper T lymphocytes (HTL) and cytotoxic T lymphocytes (CTL) are the key mediators of acute allograft rejection. This report demonstrates that the presence or absence of 'traditional' graft-reactive HTL and CTL is not necessarily related to allograft survival. In these studies, donor/recipient combinations disparate only at MHC or only at minor histocompatibility (mH) loci were employed. Allograft survival was monitored, donor-reactive IL-2 (interleukin-2) producing HTL and CTL were quantified by modified limiting dilution analysis, and serum levels of cytolytic alloantibody were determined. C57BL/10 hearts (H-2b) transplanted into B10.BR (H-2k) recipients (full MHC disparity) enjoyed prolonged survival despite massive infiltration of the allograft by donor-reactive HTL and CTL. IgM, but not IgG, donor-reactive alloantibody was present in the sera of these mice. Hence, traditional IL-2 producing HTL and CTL were not capable of mediating acute graft rejection, nor of providing help for alloantibody isotype switching in this MHC disparate combination. In contrast, C3H/HeN (H-2k) hearts transplanted into B10.BR (H-2k) recipients (mH disparity only) were acutely rejected. Donor-reactive HTL and CTL were rare or not detectable in these recipients, and cytolytic alloantibody was not detectable. Similar observations were made when B10.BR hearts were transplanted into C3H/HeN recipients. Interestingly, treatment of recipients with anti-CD4 monoclonal antibody prevented rejection of mH disparate allografts. Therefore, CD4+ T cells were required for rejection of mH disparate allografts, but this process was independent of detectable IL-2 production or CTL function. Hence, the significance of monitoring 'traditional' T cell functions should be questioned in certain donor/recipient combinations.
Assuntos
Epitopos/imunologia , Rejeição de Enxerto/imunologia , Transplante de Coração/imunologia , Isoantígenos/imunologia , Linfócitos T Citotóxicos/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Animais , Testes Imunológicos de Citotoxicidade , Feminino , Rejeição de Enxerto/genética , Sobrevivência de Enxerto/genética , Sobrevivência de Enxerto/imunologia , Isoanticorpos/biossíntese , Complexo Principal de Histocompatibilidade/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Locos Secundários de Histocompatibilidade/imunologia , Linfócitos T Auxiliares-Indutores/metabolismoRESUMO
Inhibitor development is a serious complication in haemophilia, and its treatment, immune tolerance therapy, is an expensive part of haemophilia treatment. However, the therapy can lead to an increased lifespan and improved quality of life. If commenced sufficiently early in the disease, it can help to reduce the overall amount of factor VIII concentrate, or other plasma derived therapeutic agents required during life.
Assuntos
Dessensibilização Imunológica/economia , Fator VIII/imunologia , Fator VIII/provisão & distribuição , Hemofilia A/terapia , Isoanticorpos/biossíntese , Adulto , Dessensibilização Imunológica/métodos , Fator VIII/economia , Fator VIII/uso terapêutico , Alemanha , Hemofilia A/complicações , Hemofilia A/economia , Hemofilia A/imunologia , Hemofilia B/economia , Hemofilia B/imunologia , Hemofilia B/terapia , Humanos , Seguro Saúde/legislação & jurisprudência , Artropatias/prevenção & controle , Masculino , Resultado do TratamentoRESUMO
Effective platelet support for alloimmunized refractory thrombocytopenic patients may be provided by several potential strategies, the most common being HLA-matched single-donor platelets or crossmatch-compatible, pooled random- or single-donor platelets. This study used a detailed economic analysis to compare the cost-effectiveness of several techniques for platelet crossmatching and that of HLA-matched single-donor platelets. The crossmatch methods evaluated were a microlymphocytotoxicity test (LCT), an immunofluorescence technique (PSIFT), a radioactive antiglobulin test (PRAT), and an enzyme-linked immunosorbent assay (ELISA). The analysis was based on the need to support 100 refractory patients with acute leukemia with a presumed requirement of 500 transfusions. The relative costs for a successful crossmatch were: PRAT less than LCT less than LCT + PRAT less than PSIFT less than ELISA. In the comparison of the crossmatch methods, an increase in costs was generally associated with an increase in the number of successful transfusion episodes. However, decreasing marginal gains were seen. The HLA-matched single-donor platelets were relatively cost-inefficient in comparison to the crossmatch-compatible platelets. A theoretic sequence of tests for cost-effective provision of optimal platelet support in refractory patients was evaluated. Such considerations of cost are important in the selection of an optimal program for the management of alloimmunized refractory thrombocytopenic patients.
Assuntos
Plaquetas/imunologia , Transfusão de Sangue/economia , Análise Custo-Benefício , Teste de Histocompatibilidade/economia , Isoanticorpos/análise , Trombocitopenia/terapia , Testes Imunológicos de Citotoxicidade/economia , Ensaio de Imunoadsorção Enzimática/economia , Imunofluorescência/economia , Antígenos HLA/análise , Teste de Histocompatibilidade/métodos , Humanos , Isoanticorpos/biossíntese , Distribuição Aleatória , Trombocitopenia/sangue , Trombocitopenia/economia , Reação TransfusionalRESUMO
Records from 506 hemodialysis multitransfused patients were reviewed to evaluate the incidence of transfusion induced red cell allo-immunization. Out of 405 patients having received a total of 6 608 red cell transfusions compatible for A, B and D antigens, only 7 patients (1.72%) developed allo-antibodies which may be attributed to such transfusions. Elaborate red cell phenotyping in un-immunized recipients and selection of blood units compatible for other antigens than A, B and D in an effort to prevent red cell allo-immunization to other blood group antigens in such potentially multitransfused patients does not accordingly appear to be justified and cost-effective.