RESUMO
AIM: It remains unclear, why only some patients form alloantibodies against foreign RBC antigens. Transfusion of red blood cell (RBC) products and pregnancy are the most relevant causes of immunization against RBC alloantigens. Here we investigated the relationship between RBC alloantibodies, Rh phenotype, and HLA phenotype among patients with multiple RBC alloantibodiesMETHODS: In a group of 124 multi-responders â including both pregnant women and transplant recipients â we analysed the distribution of HLA-Class II variants in subgroups of multi-responders to RBC alloantigens according to their Rh status. RESULTS: As expected, the RhD-negative phenotype was overrepresented in our alloimmunized group (49.2 %) compared to in the general population. Importantly, HLA-DRB1*15 carriers were significantly overrepresented among D-negative multi-responders compared to D-positive multi-responders (Pc = 0.045). Furthermore, the linked HLA-DRB1*13, HLA-DQB1*06, and HLA-DQA1*01 variants were more frequent in individuals with the DCCee phenotype than in other RhD-positive phenotypes. CONCLUSION: Our present findings showed that RBC multispecific alloimmunization was associated with particular HLA-Class II variants based on Rh status (Tab. 3, Ref. 22).
Assuntos
Eritrócitos , Isoanticorpos , Feminino , Cadeias HLA-DRB1/genética , Humanos , Imunização , Fenótipo , GravidezRESUMO
BACKGROUND AND OBJECTIVES: Alloimmune antibodies against red-blood-cell (RBC) antigens induced in susceptible individuals (responders) by transfusion, pregnancy or transplantation may have serious clinical consequences. The aim of this study was to investigate association of alloimmunization against selected RBC antigens with HLA-Class II. MATERIALS AND METHODS: A total of 230 responders (106 monoresponders and 124 multiresponders) were enrolled into the study. HLA-DRB1 and HLA-DQB1 variants were determined by PCR-SSO and their frequencies compared between the patients (patient subgroups) and 375 ethnically and regionally matched controls. RESULTS: Development of multiple RBC antibodies was associated with HLA-DRB1*15 and HLA-DQB1*06 allelic groups in the patients, with the relationship being particularly apparent in those with anti-C+D antibodies. Furthermore, DRB1*13 and DQB1*06 were more frequent in multiresponders with anti-E+c antibodies and DRB1*03 and DQB1*02 in those with anti-E+Cw. CONCLUSION: For the first time, we confirmed the association of HLA-DRB1*15 with RBC antibody multiresponder status and found HLA-Class II associations for three frequent RBC antibody combinations. Our data support the concept that HLA restriction plays an important role in the response to RBC alloantigens.
Assuntos
Eritrócitos/imunologia , Cadeias beta de HLA-DQ/imunologia , Cadeias HLA-DRB1/imunologia , Adulto , Alelos , República Tcheca , Feminino , Frequência do Gene , Genótipo , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Haplótipos , Humanos , Isoanticorpos/sangue , Masculino , GravidezRESUMO
Monoclonal antibodies represent a standard part in the treatment of oncologic patients, but their efficacy in multiple myeloma used to be unsatisfactory. Daratumumab monotherapy was approved by the American FDA in 2015, after unprecedented results were obtained in a heavily pre-treated group of patients. In 2016 daratumumab was approved in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of myeloma patients who have received at least one prior therapy.The toxicity of the drug is low, and is dominated by infusion-related reactions in more or less half of patients. The development as well as the management of these sometimes urgent reactions is described in depth in this review. As multiple myeloma is characterized by the presence of paraprotein (monoclonal antibody) and CD38 is a ubiquitous antigen, several unexpected complications have been reported during the administration of the drug. In this review, we aim to describe and offer some solutions for the complications that may be encountered during daratumumab treatment, such as interference with serum protein electrophoresis and immunofixation assays that may confuse the assessment of the hematological response, interference with blood compatibility testing that may cause a delay in the delivery of compatible transfusions, and difficulties that may occur in flow cytometric analysis of minimal residual disease. Because of the high activity of daratumumab and its expected widespread use, clinicians should be aware of its side effects and their management. It is also very important to inform colleagues in clinical laboratories about the initiation of daratumumab treatment in particular patient.Key words: multiple myeloma - daratumumab - infusion related reaction - flow cytometry - transfusionThis work was supported by the Czech Ministry of Education, Youth and Sports (project no. IRP- 201550) and by the Czech Ministry of Health (15-29667A).The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Accepted: 22. 8. 2016Submitted: 12. 5. 2016.
Assuntos
Anticorpos Monoclonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Mieloma Múltiplo/tratamento farmacológico , Anticorpos Monoclonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Tipagem e Reações Cruzadas Sanguíneas , Eletroforese das Proteínas Sanguíneas , Bortezomib/administração & dosagem , Dexametasona/administração & dosagem , Citometria de Fluxo , Humanos , Lenalidomida , Talidomida/administração & dosagem , Talidomida/análogos & derivadosRESUMO
TRALI is a major cause of serious morbidity and mortality associated with a blood transfusion. It is clinically manifested by acute respiratory distress within 6 hours of completion of transfusion. Neutrophils have the key role in the pathogenesis. They are activated mostly with leukocyte antibodies (HLA and granulocyte) that are present mainly in plasma containing blood products. TRALI is a clinical diagnosis based on hypoxemia and positive finding on lung X-ray examination. The treatment is only supportive and the mortality is about 5% to 10%. The major preventive measure is transfusing blood products from donors without leukocyte antibodies.
Assuntos
Lesão Pulmonar Aguda , Reação Transfusional , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/mortalidade , Lesão Pulmonar Aguda/terapia , HumanosRESUMO
Thrombotic thrombocytopenic purpura (TTP) was first described by Eli Moschcowitz in 1924. The pathophysiology of this disease is related to unusual, large multimers of von Willebrand factor in microcirculation, that are insufficiently cleaved by ADAMTS13 protease (a disintegrin-like and metalloprotease with thrombospondin type 1motif,13). Congenital TTP/Upshaw-Schulman syndrome is less frequent than acquired one TTP/HUS (haemolytic-ureamic syndrome). Short characteristic of patients with inherited form of TTP is reported as well as their clinical and laboratory features and management of treatment.
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Púrpura Trombocitopênica Trombótica/congênito , Adolescente , Adulto , República Tcheca/epidemiologia , Feminino , Síndrome Hemolítico-Urêmica/epidemiologia , Síndrome Hemolítico-Urêmica/genética , Humanos , Incidência , Masculino , Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Therapeutic plasma exchange is the treatment of choice for thrombotic thrombocytopenic purpura (TTP). METHODS AND RESULTS: Patients chronically treated with plasma exchange are frequently exposed to a large number of single plasma donors units, however successful clinical and laboratory improvement is generally achieved. Therapeutic plasma exchange significantly decreased mortality of this disease. Plasma treatment offers two possibilities--plasma infusion or plasma exchange and possibility of different plasma types. Cryoprecipitate-poor plasma was introduced as better form of FFP, however studies presented later did not confirm the therapeutic benefit. Quarantine FFP is widely used for patients with TTP in the Czech Republic; this type is tested frequently for negativity of human immunodeficiency virus, hepatitis B virus, hepatitis C virus and syphilis. Treatment with pathogen inactivated plasma (e.g., solvent detergent plasma, methylen-blue plasma, psoralen treated plasma or riboflavin treated plasma) is not frequently used in the Czech Republic. Authors present different plasma types and their experience with plasma treatment in seven patients with congenital form of TTP. CONCLUSIONS: In five patients therapeutic plasma exchange with quarantine fresh frozen plasma uas used. During each treatment 1.5 of plasma volume was exchanged. Two patients--teenagers were treated at the ex paediatric clinic with plasma infusion in regularly 2 weeks intervals.
Assuntos
Troca Plasmática , Púrpura Trombocitopênica Trombótica/terapia , Adolescente , Adulto , Feminino , Humanos , Masculino , Púrpura Trombocitopênica Trombótica/genética , Adulto JovemRESUMO
We present an example of a patient with confirmed cold agglutinin disease who underwent cardiac surgery in hypothermia to illustrate a known fact that, when exposed to cold, cold agglutinins induce haemolysis of erythrocytes and that cryoglobulins and cryofibrinogens may, upon exposition to cold during a surgery under hypothermia, precipitate or gelify and thus increase plasma viscosity and damage microcirculation. Detailed immunological and haematological investigations in all patients awaiting cardiac surgery with a risk of developing hypothermia is not advantageous considering the low number of patients with clinical and laboratory signs of cold agglutinin disease, autoimmune haemolytic anaemia or paroxysmal cold haemoglobinuria and considering that these investigations, in addition, might not detect cryoglobulinaemia and cryofibrinogenemia. Identification of in-risk patients from the warning signs in the medical history, physical or basal laboratory testing who would subsequently undergo confirmatory investigations to verify the presence of these entities and define them accurately might be a potential solution to this clinical issue. Cardiac surgery strategy and peri-operative care should be tailored to the results of these investigations. Well-structured, practiced and functional cooperation between clinicians and laboratory personnel is a prerequisite for success in these circumstances.