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2.
Transfusion ; 62(9): 1727-1730, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35841199

RESUMO

BACKGROUND: Prior studies have shown that sickle cell trait (SCT) is the most common reason attributed to leukoreduction (LR) filter failure due to physical blockage. However, current Food and Drug Administration (FDA) guidelines do not require blood collectors to take a specific action to mitigate inadequate LR that may occur among donors with SCT. We sought to determine the scope of inadequate LR among whole blood (WB) donations collected from individuals with SCT and processed under standard manufacturing conditions. STUDY DESIGN AND METHODS: Between 8/2021 and 2/2022, a total of 40 red blood cells units (RBCs) manufactured from WB donations collected from donors historically positive for SCT had residual leukocyte testing performed. All 40 of the units had appeared to successfully complete leukofiltration. RESULTS: Out of the 40 units tested, 22 failed routine residual leukocyte quality control testing (55% failure rate, 95% confidence interval 40%-70%). Nine out of the 22 failures resulted in more than 100 residual leukocytes per microliter of product. CONCLUSION: Even when leukofiltration appears to have been completed successfully, WB units collected from donors with SCT have a high (55% in aggregate) rate of inadequate leukoreduction. Correlating this result with previous studies showing that of up to 50% of WB units collected from donors with SCT fail to pass through the leukoreduction filter, we estimate that only 25% of WB donations collected from individuals with SCT will result in a leukoreduced RBC unit that meets all FDA requirements. Blood centers should encourage individuals with SCT to donate platelets or plasma, rather than WB.


Assuntos
Doadores de Sangue , Traço Falciforme , Preservação de Sangue/métodos , Humanos , Procedimentos de Redução de Leucócitos/métodos , Controle de Qualidade
3.
Transfusion ; 62 Suppl 1: S98-S104, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35748674

RESUMO

BACKGROUND: There is increasing interest in leukoreduced whole blood (WB) as a transfusion product for trauma patients. In some jurisdictions, few leukoreduced filters are approved or appropriate for WB leukoreduction and quality information is therefore limited. This study assessed the impact of filtration timing of WB collected in CPDA-1 versus CPD on in vitro quality. STUDY DESIGN AND METHODS: WB was collected in CPDA-1 or CPD and leukoreduction filtered either after 3-8 h (early) or 18-24 h (late) from stop bleed time. In vitro quality was assessed after filtration and throughout 5 weeks of storage at 4°C. Cell count and hemoglobin levels were determined by hematology analyzer, platelet activation and responsiveness to ADP by surface expression of P-selectin by flow cytometry, hemolysis by HemoCue, and metabolic parameters by blood gas analyzer. Hemostatic properties were assessed by rotational thromboelastometry. Plasma protein activities and clotting times were determined by automated coagulation. RESULTS: Although there were some data points which showed statistically significant differences associated with anticoagulant choices or the filtration timing, no general trend in inferiority/performance could be discerned. After 35 days' storage, only clotting time, alpha angle and factor II in the early filtration arm comparing anticoagulants and prothrombin time and factor II in the CPDA-1 study arm comparing filtration timing showed a significant difference. CONCLUSION: In vitro WB quality seems to be independent on the choice of anticoagulant and filtration timing supporting WB hold-times to up to 24 h, increasing operational flexibility for transfusion services.


Assuntos
Preservação de Sangue , Procedimentos de Redução de Leucócitos , Anticoagulantes/metabolismo , Anticoagulantes/farmacologia , Plaquetas/metabolismo , Humanos , Protrombina
4.
Hematol., Transfus. Cell Ther. (Impr.) ; 43(4): 494-498, Oct.-Dec. 2021. ilus
Artigo em Inglês | LILACS | ID: biblio-1350801

RESUMO

ABSTRACT Introduction: Peripheral blood leukocytes are a suitable cell model for science research. However, blood samples from healthy volunteers are limited in volume and difficult to obtain due to the complexity of volunteer recruitment. Objective: Therefore, it is urgent to find an alternative source of peripheral blood leukocytes. Method: One of the possibilities is the use of leukocyte reduction filters (LRFs) in blood banks that is used for preparation of leukoreduced blood products. More than 90% of the leukocytes are trapped in the leukofilters allowing the desired blood product to pass through. Results: It has been reported that the biological function of leukocytes collected from the filters are no different from those isolated from buffy coats, leukapheresis products and whole blood (WB) cells. Moreover, LRFs are waste products that are discarded after leukoreduction. Conclusion: Thus, leukofilters represent an economic source of human cell populations that can be used for a variety of investigative purposes, with no cost. In the present study, we reviewed the different usage of LRFs in the research, clinical and commercial applications.


Assuntos
Procedimentos de Redução de Leucócitos , Leucócitos
5.
Br J Haematol ; 195(5): 681-688, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34490619

RESUMO

Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare, commonly fatal complication of transfusion preventable by irradiation of blood units. The revision of the Dutch transfusion guideline addressed the question whether irradiation is still necessary if blood components are prestorage leukodepleted. We searched for published cases of TA-GVHD following transfusion of prestorage leukodepleted blood and through contacting haemovigilance systems. Six presumed cases were found, dating from 1998 to 2013. Four out of six patients had received one or more non-irradiated units despite recognised indications for irradiated blood components. In the countries providing information, over 50 million prestorage leukodepleted, non-irradiated, non-pathogen-reduced cellular components were transfused in a 10-year period. Potential benefits of lifting indications for irradiation were considered. These include reduced irradiation costs (€ 1.5 million annually in the Netherlands) and less donor exposure for neonates. Findings were presented in an invitational expert meeting. Recommendations linked to human leukocyte antigen similarity between donor and recipient or intra-uterine transfusion were left unchanged. Indications linked to long-lasting deep T-cell suppression were defined with durations of 6 or 12 months after end of treatment (e.g. autologous or allogeneic stem cell transplantation). Need for continued alertness to TA-GVHD and haemovigilance reporting of erroneous non-irradiated transfusions was emphasised.


Assuntos
Transfusão de Componentes Sanguíneos/efeitos adversos , Preservação de Sangue , Reação Transfusional/etiologia , Reação Transfusional/prevenção & controle , Transfusão de Componentes Sanguíneos/métodos , Preservação de Sangue/efeitos adversos , Preservação de Sangue/métodos , Transfusão de Sangue , Humanos , Procedimentos de Redução de Leucócitos/métodos , Países Baixos/epidemiologia
6.
Transfusion ; 61 Suppl 2: S11-S35, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34337759

RESUMO

INTRODUCTION: Supplemental data from the 2019 National Blood Collection and Utilization Survey (NBCUS) are presented and include findings on donor characteristics, autologous and directed donations and transfusions, platelets (PLTs), plasma and granulocyte transfusions, pediatric transfusions, transfusion-associated adverse events, cost of blood units, hospital policies and practices, and implementation of blood safety measures, including pathogen reduction technology (PRT). METHODS: National estimates were produced using weighting and imputation methods for a number of donors, donations, donor deferrals, autologous and directed donations and transfusions, PLT and plasma collections and transfusions, a number of crossmatch procedures, a number of units irradiated and leukoreduced, pediatric transfusions, and transfusion-associated adverse events. RESULTS: Between 2017 and 2019, there was a slight decrease in successful donations by 1.1%. Donations by persons aged 16-18 decreased by 10.1% while donations among donors >65 years increased by 10.5%. From 2017 to 2019, the median price paid for blood components by hospitals for leukoreduced red blood cell units, leukoreduced apheresis PLT units, and for fresh frozen plasma units continued to decrease. The rate of life-threatening transfusion-related adverse reactions continued to decrease. Most whole blood/red blood cell units (97%) and PLT units (97%) were leukoreduced. CONCLUSION: Blood donations decreased between 2017 and 2019. Donations from younger donors continued to decline while donations among older donors have steadily increased. Prices paid for blood products by hospitals decreased. Implementation of PRT among blood centers and hospitals is slowly expanding.


Assuntos
Doadores de Sangue/estatística & dados numéricos , Pesquisas sobre Atenção à Saúde , Adolescente , Adulto , Distribuição por Idade , Idoso , Bancos de Sangue/estatística & dados numéricos , Remoção de Componentes Sanguíneos/estatística & dados numéricos , Transfusão de Componentes Sanguíneos/estatística & dados numéricos , Transfusão de Componentes Sanguíneos/tendências , Doadores de Sangue/provisão & distribuição , Antígenos de Grupos Sanguíneos/genética , Transfusão de Sangue/estatística & dados numéricos , Transfusão de Sangue/tendências , Transfusão de Sangue Autóloga/estatística & dados numéricos , Transfusão de Sangue Autóloga/tendências , Área Programática de Saúde , Criança , Pré-Escolar , Transmissão de Doença Infecciosa/prevenção & controle , Seleção do Doador/estatística & dados numéricos , Feminino , Custos de Cuidados de Saúde , Hospitais/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Procedimentos de Redução de Leucócitos/economia , Procedimentos de Redução de Leucócitos/métodos , Masculino , Pessoa de Meia-Idade , Política Organizacional , Assunção de Riscos , Amostragem , Procedimentos Cirúrgicos Operatórios/estatística & dados numéricos , Reação Transfusional/epidemiologia , Estados Unidos/epidemiologia , Adulto Jovem
7.
Transfusion ; 61 Suppl 1: S80-S89, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34269444

RESUMO

BACKGROUND: Collection of non-leukoreduced citrate-phosphate-dextrose-adenine (CPDA-1) whole blood is performed in walking blood banks. Blood collected under field conditions may have increased risk of bacterial contamination. This study was conducted to examine the effects of WBC reduction and storage temperature on growth of Escherichia coli (ATCC® 25922™) in CPDA-1 whole blood. METHODS: CPDA-1 whole blood of 450 ml from 10 group O donors was inoculated with E. coli. Two hours after inoculation, the test bags were leukoreduced with a platelet-sparing filter. The control bags remained unfiltered. Each whole blood bag was then split into three smaller bags for further storage at 2-6°C, 20-24°C, or 33-37°C. Bacterial growth was quantified immediately, 2 and 3 h after inoculation, on days 1, 3, 7, and 14 for all storage temperatures, and on days 21 and 35 for storage at 2-6°C. RESULTS: Whole blood was inoculated with a median of 19.5 (range 12.0-32.0) colony-forming units per ml (CFU/ml) E. coli. After leukoreduction, a median of 3.3 CFU/ml (range 0.0-33.3) E. coli remained. In the control arm, the WBCs phagocytized E. coli within 24 h at 20-24°C and 33-37°C in 9 of 10 bags. During storage at 2-6°C, a slow self-sterilization occurred over time with and without leukoreduction. CONCLUSIONS: Storage at 20-24°C and 33-37°C for up to 24 h before leukoreduction reduces the risk of E. coli-contamination in CPDA-1 whole blood. Subsequent storage at 2-6°C will further reduce the growth of E. coli.


Assuntos
Preservação de Sangue , Segurança do Sangue , Infecções por Escherichia coli/microbiologia , Escherichia coli/crescimento & desenvolvimento , Procedimentos de Redução de Leucócitos , Adenina/química , Preservação de Sangue/métodos , Citratos/química , Escherichia coli/isolamento & purificação , Glucose/química , Humanos , Temperatura
8.
Transfusion ; 61 Suppl 1: S131-S143, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34269454

RESUMO

BACKGROUND: Leukoreduced whole blood (LR-WB) has received renewed attention as alternative to component-based transfusion in trauma. According to the manufacturer's instructions, leukoreduction should be carried out within 8 h after collection. This study assessed impact of (1) WB collection bag, (2) LR filtration, and (3) timing of filtration on in vitro quality. STUDY DESIGN AND METHODS: WB collected into different vendor bags was held at room temperature for <8 h or >16 h but <24 h prior to LR. In vitro quality was assessed before and after filtration, and throughout 3 weeks of storage at 4°C. Cell count and hemoglobin levels were determined by hematology analyzer, platelet activation, and responsiveness to ADP by surface expression of P-selectin by flow cytometry, hemolysis by HemoCue, and metabolic parameters by blood gas analyzer. Hemostatic properties were assessed by rotational thromboelastometry. Plasma protein activities and clotting times were determined by automated coagulation analyzer or quantitative immunoblotting. RESULTS: Bag type had no impact on WB in vitro quality. LR by filtration had some impact, but is aligned with data in the literature. The time between donation and filtration resulted in some statistically significant differences in metabolic activity, platelet yield, platelet activation, and factor protein activity initially; however, these differences in in vitro quality attributes decreased throughout 21-day cold storage. CONCLUSION: WB hold time showed only a minor impact on WB in vitro quality, so it may be possible for blood processing facilities to explore extended hold times prior to filtration in order to provide greater operational flexibility.


Assuntos
Preservação de Sangue/métodos , Contagem de Células Sanguíneas , Temperatura Baixa , Hemólise , Hemostasia , Humanos , Procedimentos de Redução de Leucócitos/métodos , Ativação Plaquetária , Tromboelastografia
9.
Transfusion ; 61 Suppl 1: S90-S100, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34269461

RESUMO

BACKGROUND: Recent studies characterizing in vitro hemostatic properties of whole blood (WB) leukoreduced (LR) with a platelet-sparing filter have described subtle, if any, changes to viscoelastic clotting; however, reductions in platelet (PLT) content and impedance aggregometry (IA) responses have been noted. The effects of filtration of WB (i.e., filter-contact effects, reduction in platelet and leukocyte count) have not been rigorously investigated as to their individual impacts on platelet IA responses. STUDY DESIGN AND METHODS: WB units from healthy donors were collected and characterized to assess the effects of platelet-sparing leukoreduction (LR) upon the in vitro hemostatic measures of platelet IA and thromboelastometry. Further characterization of platelet IA responses was carried out in WB samples to delineate the effects of platelet count and leukocyte presence/absence upon the response. RESULTS: WB filtration reduced the platelet count and IA responses but had no impact on viscoelastic clotting measures in fresh WB. Experiments revealed that IA responses have a linear correlation with platelet count in both apheresis platelets and WB and that passage of platelets through the WB-LR filter has no impact upon the strength of this response. Further experiments in LR WB showed that addition of autologous leukocytes back to the platelets fully restored the platelet aggregation response to pre-filtration levels. CONCLUSION: WB filtration results in platelet count reduction and leukocyte removal; however, platelet IA is not degraded by passage through the filter. Apparent declines in platelet IA responses can be fully attributed to the reduction in platelet count and the removal of leukocytes.


Assuntos
Plaquetas/citologia , Leucócitos/citologia , Agregação Plaquetária , Hemostasia , Humanos , Procedimentos de Redução de Leucócitos , Contagem de Plaquetas , Testes de Função Plaquetária , Tromboelastografia
10.
PLoS One ; 16(7): e0254615, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34297742

RESUMO

Leukocytes have an essential role in patient clinical trajectories and progression. Traditional methods of leukocyte enrichment have many significant limitations for current applications. It is demonstrated a novel 3D printing leukocyte sorting accumulator that combines with centrifugation to ensure label-free initial leukocyte enrichment based on cell density and size. The internal structure of leukocyte sorting accumulator (revealed here in a new design, leukocyte sorting accumulator-3, upgraded from earlier models), optimizes localization of the buffy coat fraction and the length of the period allocated for a second centrifugation step to deliver a higher recovery of buffy coats than earlier models. Established methodological parameters were evaluated for reliability by calculating leukocyte recovery rates and erythrocyte depletion rates by both pushing and pulling methods of cell displacement. Results indicate that leukocyte sorting accumulator-3 achieves a mean leukocytes recovery fraction of 96.2 ± 2.38% by the pushing method of layer displacement. By the pulling method, the leukocyte sorting accumulator-3 yield a mean leukocytes recovery fraction of 94.4 ± 0.8%. New procedures for preliminary enrichment of leukocytes from peripheral blood that avoid cellular damage, as well as avert metabolic and phase cycle intervention, are required as the first step in many modern clinical and basic research assays.


Assuntos
Procedimentos de Redução de Leucócitos/métodos , Leucócitos/citologia , Impressão Tridimensional/instrumentação , Buffy Coat/classificação , Buffy Coat/citologia , Centrifugação/instrumentação , Centrifugação/métodos , Humanos , Procedimentos de Redução de Leucócitos/instrumentação , Leucócitos/classificação
12.
Transfusion ; 61(9): 2556-2565, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34169541

RESUMO

BACKGROUND: The temperature at which filtration takes place has been reported to influence the efficacy of leukoreduction. We aimed to compare the residual leukocyte count (RLC) in red cell units (RCUs) filtered at cold (CT) versus room temperature (RT) and to assess whether this correlates clinically with a difference in the incidence of acute transfusion reactions (ATRs). METHODS AND MATERIALS: In the first part of the study, whole blood units collected were randomly allocated for subsequent filtration at CT and RT, respectively. RLC postfiltration was assessed using flow cytometry. The second part of the study was a nonrandomized clinical trial in which incidence of ATR was compared between RCUs filtered at RT and CT for 6 months each. RESULTS: Thirty-five RCUs each underwent leukofiltration at CT and RT, respectively. The median RLCs in the filtered units at CT and RT were 0.02 × 106 and 0.1 × 106 leukocytes/unit, respectively (p = .0001), with no difference in red blood cell (RBC) recovery (p = .41). During the second part, 3455 RCUs filtered at RT and 3539 RCUs filtered at CT were transfused to patients. The rate of febrile non-hemolytic transfusion reaction (FNHTR) among transfused patients was less with units filtered at CT (1 per 2000 transfusions) in comparison to RT (1 per 588 transfusions). The difference was, however, not significant (p = .14). CONCLUSION: If change in temperature alone can cause significant reduction in leukocytes, then it is a simple way to curtail the rate of this common yet unpleasant reaction and reduce the reaction rate at minimal cost.


Assuntos
Preservação de Sangue , Eritrócitos/citologia , Procedimentos de Redução de Leucócitos , Adulto , Preservação de Sangue/métodos , Temperatura Baixa , Transfusão de Eritrócitos/efeitos adversos , Transfusão de Eritrócitos/métodos , Feminino , Humanos , Procedimentos de Redução de Leucócitos/métodos , Masculino , Reação Transfusional/etiologia , Adulto Jovem
13.
Transfusion ; 61(6): 1729-1739, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33948969

RESUMO

BACKGROUND: The average hemoglobin content of red cell concentrates (RCC) varies depending on the method of preparation. Surprisingly less data are available concerning the clinical impact of those differences. STUDY DESIGN AND METHODS: The effects of two types of RCC (RCC-A, RCC-B) on transfusion regime were compared in a non-blinded, prospective, randomized, two-period, and crossover clinical trial. RCC-A was obtained by whole blood leukoreduction and subsequent plasma removal, RCC-B removing plasma and buffy coat first, followed by leukoreduction. Eligible patients were adult, with transfusion-dependent thalassemia (TDT). RESULTS: RCC-A contained 63.9 (60.3-67.8) grams of hemoglobin per unit (median with 1st and 3rd quartile), RCC-B 54.5 (51.0-58.2) g/unit. Fifty-one patients completed the study. With RCC-B, the average pre-transfusion hemoglobin concentration was 9.3 ± 0.5 g/dl (mean ± SD), the average transfusion interval 14.2 (13.7-16.3) days, the number of RCC units transfused per year 39.3 (35.4-47.3), and the transfusion power index (a composite index) 258 ± 49. With RCC-A, the average pre-transfusion hemoglobin concentration was 9.6 ± 0.5 g/dl (+2.7%, effect size 0.792), the average transfusion interval 14.8 (14.0-18.5) days (+4.1%, effect size 0.800), the number of RCC units transfused per year 34.8 (32.1-42.5) (-11.4%, effect size -1.609), and the transfusion power index 272 ± 61 (+14.1%, effect size 0.997). All differences were statistically highly significant (p < .00001). The frequency of transfusion reactions was 0.59% with RCC-A and 0.56% with RCC-B (p = 1.000). CONCLUSION: To reduce the number of RCC units consumed per year and the number of transfusion episodes, TDT patients should receive RCC with the highest average hemoglobin content.


Assuntos
Transfusão de Eritrócitos/métodos , Hemoglobinas/análise , Talassemia/terapia , Adulto , Estudos Cross-Over , Transfusão de Eritrócitos/efeitos adversos , Eritrócitos/química , Eritrócitos/citologia , Feminino , Humanos , Procedimentos de Redução de Leucócitos , Masculino , Pessoa de Meia-Idade , Plasmaferese , Estudos Prospectivos , Talassemia/sangue , Reação Transfusional/etiologia , Resultado do Tratamento
14.
J Cardiothorac Surg ; 16(1): 58, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33771192

RESUMO

BACKGROUND: Acute Kidney Injury (AKI) adversely affects outcomes after cardiac surgery. A major mediator of AKI is the activation of leukocytes through exposure to the cardiopulmonary bypass circuit. We evaluate the use of leukodepletion filters throughout bypass to protect against post-operative AKI by removing activated leukocytes during cardiac surgery. METHODS: This is a single-centre, double-blind, randomized controlled trial comparing the use of leukodepletion versus a standard arterial filter throughout bypass. Elective adult patients undergoing heart valve surgery with or without concomitant procedures were investigated. The primary clinical outcome measured was the development of AKI according to the KDIGO criteria. Secondary measures included biomarkers of renal tubular damage (urinary Retinol Binding Protein and Kidney Injury Molecule-1), glomerular kidney injury (urinary Micro Albumin and serum Cystatin C) and urinary Neutrophil Gelatinase Associated Lipocalin, as well as the length of hospital stay and quality of life measures through EQ-5D-5L questionnaires. RESULTS: The ROLO trial randomized 64 participants with a rate of recruitment higher than anticipated (57% achieved, 40% anticipated). The incidence of AKI was greater in the leukodepletion filter group (44% versus 23%, risk difference 21, 95% CI - 2 to 44%). This clinical finding was supported by biomarker levels especially by a tendency toward glomerular insult at 48 h, demonstrated by a raised serum Cystatin C (mean difference 0.11, 95% CI 0.00 to 0.23, p = 0.068) in the leukodepleted group. There was however no clear association between the incidence or severity of AKI and length of hospital stay. On average, health related quality of life returned to pre-operative levels in both groups within 3 months of surgery. CONCLUSIONS: Leukocyte depletion during cardiopulmonary bypass does not significantly reduce the incidence of AKI after valvular heart surgery. Other methods to ameliorate renal dysfunction after cardiac surgery need to be investigated. TRIAL REGISTRATION: The trial was registered by the International Standard Randomized Controlled Trial Number Registry ISRCTN42121335 . Registered on the 18 February 2014. The trial was run by the Bristol Clinical Trials and Evaluation Unit. This trial was financially supported by the National Institute of Health Research (Research for Patient Benefit), award ID: PB-PG-0711-25,090.


Assuntos
Injúria Renal Aguda/prevenção & controle , Procedimentos Cirúrgicos Cardíacos/métodos , Doenças das Valvas Cardíacas/cirurgia , Valvas Cardíacas/cirurgia , Procedimentos de Redução de Leucócitos/métodos , Qualidade de Vida , Injúria Renal Aguda/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Feminino , Humanos , Período Intraoperatório , Testes de Função Renal , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
15.
Am J Respir Cell Mol Biol ; 64(5): 569-578, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33571420

RESUMO

Pneumonia-induced lung injury and acute respiratory distress syndrome can develop because of an inappropriate inflammatory response to acute infections, leading to a compromised alveolar barrier. Recent work suggests that hospitalized patients with allergies/asthma are less likely to die of pulmonary infections and that there is a correlation between survival from acute respiratory distress syndrome and higher eosinophil counts; thus, we hypothesized that eosinophils associated with a type 2 immune response may protect against pneumonia-induced acute lung injury. To test this hypothesis, mice were treated with the type 2-initiating cytokine IL-33 intratracheally 3 days before induction of pneumonia with airway administration of a lethal dose of Staphylococcus aureus. Interestingly, IL-33 pretreatment promoted survival by inhibiting acute lung injury: amount of BAL fluid proinflammatory cytokines and pulmonary edema were both reduced, with an associated increase in oxygen saturation. Pulmonary neutrophilia was also reduced, whereas eosinophilia was strongly increased. This eosinophilia was key to protection; eosinophil reduction eliminated both IL-33-mediated protection against mortality and inhibition of neutrophilia and pulmonary edema. Together, these data reveal a novel role for eosinophils in protection against lung injury and suggest that modulation of pulmonary type 2 immunity may represent a novel therapeutic strategy.


Assuntos
Lesão Pulmonar Aguda/imunologia , Eosinófilos/imunologia , Interleucina-33/imunologia , Pneumonia Estafilocócica/imunologia , Edema Pulmonar/imunologia , Síndrome do Desconforto Respiratório/imunologia , Staphylococcus aureus/patogenicidade , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/microbiologia , Lesão Pulmonar Aguda/prevenção & controle , Animais , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Toxina Diftérica/farmacologia , Modelos Animais de Doenças , Eosinófilos/efeitos dos fármacos , Feminino , Expressão Gênica , Humanos , Interleucina-33/genética , Interleucina-33/farmacologia , Interleucina-5/deficiência , Interleucina-5/genética , Interleucina-5/imunologia , Contagem de Leucócitos , Procedimentos de Redução de Leucócitos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Pneumonia Estafilocócica/complicações , Pneumonia Estafilocócica/microbiologia , Pneumonia Estafilocócica/mortalidade , Edema Pulmonar/complicações , Edema Pulmonar/microbiologia , Edema Pulmonar/mortalidade , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/microbiologia , Síndrome do Desconforto Respiratório/prevenção & controle , Staphylococcus aureus/imunologia , Análise de Sobrevida
16.
Transfusion ; 61(4): 1247-1257, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33481275

RESUMO

BACKGROUND: Irradiation of red blood cells (RBCs) inactivates residual donor T lymphocytes to prevent transfusion-associated graft-vs-host disease (TA-GVHD) but can have adverse effects on recipients and inventory management. Reported incidence of TA-GVHD is lower when leukoreduced RBCs and older blood products are transfused; therefore, the impact of leukoreduction and storage was evaluated as an alternative prevention strategy. STUDY DESIGN AND METHODS: Effectiveness of leukoreduction filters on white blood cell (WBC) proliferation was evaluated by filtering buffy coat (BC) products and isolating residual WBCs. Additionally, leukoreduced RBCs were spiked with 5 × 106 WBCs on Day 21 of hypothermic storage, then stored and processed on Days 7, 14, and 21 to obtain residual WBCs to investigate the impact of hypothermic storage on their viability and proliferative ability. Viability of residual WBCs was assessed by staining with annexin V and an antibody cocktail for flow cytometry analysis. Proliferative ability was assessed by placing carboxyfluorescein diacetate succinimidyl ester-labeled residual WBCs into culture for 6 days with phytohemagglutinin before flow cytometry assessment. RESULTS: Filtration of BC units depleted WBCs, particularly T lymphocytes, to 0.001% ± 0.003% cells/unit, although proliferative activity remained consistent with prefiltration levels of WBCs. WBCs in stored RBCs remained viable even on Day 21 of storage; however, the proliferative activity decreased to 0.24% ± 0.41%. CONCLUSIONS: Hypothermic storage of RBCs for 21 days or more is sufficient to inactivate T lymphocytes, which may help prevent TA-GVHD when irradiated RBCs are not available.


Assuntos
Criobiologia/métodos , Eritrócitos/fisiologia , Procedimentos de Redução de Leucócitos/métodos , Reação Transfusional/prevenção & controle , Preservação de Sangue/métodos , Proliferação de Células/fisiologia , Proliferação de Células/efeitos da radiação , Transfusão de Eritrócitos/efeitos adversos , Eritrócitos/efeitos da radiação , Filtração , Citometria de Fluxo/métodos , Humanos , Incidência , Procedimentos de Redução de Leucócitos/estatística & dados numéricos , Leucócitos/imunologia , Linfócitos T/imunologia , Linfócitos T/efeitos da radiação , Fatores de Tempo , Reação Transfusional/epidemiologia , Reação Transfusional/imunologia
17.
Transfusion ; 61(2): 435-448, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33146433

RESUMO

BACKGROUND: Obesity is a global pandemic characterized by multiple comorbidities, including cardiovascular and metabolic diseases. The aim of this study was to define the associations between blood donor body mass index (BMI) and RBC measurements of metabolic stress and hemolysis. STUDY DESIGN AND METHODS: The associations between donor BMI (<25 kg/m2 , normal weight; 25-29.9 kg/m2 , overweight; and ≥30 kg/m2 , obese) and hemolysis (storage, osmotic, and oxidative; n = 18 donors) or posttransfusion recovery (n = 14 donors) in immunodeficient mice were determined in stored leukocyte-reduced RBC units. Further evaluations were conducted using the National Heart, Lung, and Blood Institute RBC-Omics blood donor databases of hemolysis (n = 13 317) and metabolomics (n = 203). RESULTS: Evaluations in 18 donors revealed that BMI was significantly (P < 0.05) and positively associated with storage and osmotic hemolysis. A BMI of 30 kg/m2 or greater was also associated with lower posttransfusion recovery in mice 10 minutes after transfusion (P = 0.026). Multivariable linear regression analyses in RBC-Omics revealed that BMI was a significant modifier for all hemolysis measurements, explaining 4.5%, 4.2%, and 0.2% of the variance in osmotic, oxidative, and storage hemolysis, respectively. In this cohort, obesity was positively associated (P < 0.001) with plasma ferritin (inflammation marker). Metabolomic analyses on RBCs from obese donors (44.1 ± 5.1 kg/m2 ) had altered membrane lipid composition, dysregulation of antioxidant pathways (eg, increased oxidized lipids, methionine sulfoxide, and xanthine), and dysregulation of nitric oxide metabolism, as compared to RBCs from nonobese (20.5 ± 1.0 kg/m2 ) donors. CONCLUSIONS: Obesity is associated with significant changes in RBC metabolism and increased susceptibility to hemolysis under routine storage of RBC units. The impact on transfusion efficacy warrants further evaluation.


Assuntos
Doadores de Sangue , Preservação de Sangue/métodos , Eritrócitos/metabolismo , Obesidade/sangue , Adulto , Animais , Índice de Massa Corporal , Temperatura Baixa , Membrana Eritrocítica/química , Transfusão de Eritrócitos , Eritrócitos/citologia , Feminino , Ferritinas/sangue , Testes Hematológicos , Hemólise/fisiologia , Humanos , Procedimentos de Redução de Leucócitos , Masculino , Lipídeos de Membrana/sangue , Metaboloma , Camundongos , Camundongos Endogâmicos NOD , Óxido Nítrico/sangue , Pressão Osmótica , Estresse Oxidativo
18.
J Cardiovasc Transl Res ; 14(2): 338-347, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32681452

RESUMO

Previous experiments demonstrated improved outcome following prolonged cerebral ischemia given controlled brain reperfusion using extracorporeal circulation. The current study further investigates this. Young adult pigs were exposed to 30 min of global normothermic cerebral ischemia, achieved through intrathoracic clamping of cerebral arteries, followed by 20 min of isolated mechanical brain reperfusion. Leukocyte-filtered blood was delivered by a roller-pump at fixed pressure and flow. One experimental group additionally had a custom-made buffer solution delivered at 1:8 ratio with the blood. Hemodynamics including intracranial pressure were monitored. Blood gases were from peripheral arteries and the sagittal sinus, and intraparenchymal brain microdialysis was performed. The brains were examined by a neuropathologist. The group with the added buffer showed lower intracranial pressure as well as decreased intraparenchymal glycerol and less signs of excitotoxicity and ischemia, although histology revealed similar degrees of injury. A customized mechanical reperfusion improves multiple parameters after prolonged normothermic global cerebral ischemia. Graphical Abstract The current study investigates if it possible to improve neurological outcomes following prolonged global brain ischemia. The results indicate that a customized mechanical reperfusion protocol can attenuate neurological injury.


Assuntos
Transfusão de Sangue , Lesões Encefálicas/prevenção & controle , Isquemia Encefálica/terapia , Encéfalo/irrigação sanguínea , Procedimentos de Redução de Leucócitos , Traumatismo por Reperfusão/prevenção & controle , Reperfusão , Animais , Encéfalo/patologia , Lesões Encefálicas/sangue , Lesões Encefálicas/etiologia , Lesões Encefálicas/fisiopatologia , Isquemia Encefálica/sangue , Isquemia Encefálica/fisiopatologia , Circulação Cerebrovascular , Modelos Animais de Doenças , Hemodinâmica , Reperfusão/efeitos adversos , Traumatismo por Reperfusão/sangue , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/fisiopatologia , Sus scrofa , Fatores de Tempo
19.
Transfusion ; 61(2): 449-463, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33231302

RESUMO

BACKGROUND: For reasons unclear, some stored red blood cells (RBCs) have low hemolysis, while others have high hemolysis, which impacts quality consistency. To identify variables that influence hemolysis, routine quality control (QC) data for 42-days-stored RBCs with corresponding donor information were analyzed. STUDY DESIGN AND METHODS: RBC QC and donor data were obtained from a national blood supplier. Regression models and analyses were performed on total cohort stratified by donor sex and by high hemolysis (≥90th percentile) vs control (<90th percentile) samples, including matching. RESULTS: Data included 1734 leukoreduced RBCs (822 female, 912 male), processed by buffy coat-poor or whole blood filtration methods. Male RBCs had larger volume, hemoglobin content, and higher hemolysis than female RBCs (median hemolysis, 0.24% vs 0.21%; all P < .0001). Multivariable regression identified increased body mass index (BMI) and RBC variables were associated with higher hemolysis (P < .0001), along with older female age and buffy coat-poor processing method (P < .002). Logistic regression models comparing the high and control hemolysis subsets, matched for RBC component variables and processing method, identified overweight-obese BMI (>27 kg/m2 ) in males remained the single donor-related variable associated with higher hemolysis (P < .0001); odds ratio, 3 (95% confidence interval [CI], 1.3-6.7), increasing to 4 (95% CI, 1.8-8.6) for obese males (BMI > 30 kg/m2 ). Female donor obesity and older age trended toward higher hemolysis. CONCLUSION: Donor BMI, sex, and female age influence the level of hemolysis of 42-days-stored RBCs. Other factors, not identified in this study, also influence the level of hemolysis.


Assuntos
Doadores de Sangue , Preservação de Sangue , Índice de Massa Corporal , Eritrócitos/citologia , Hemólise , Sobrepeso/sangue , Adolescente , Adulto , Fatores Etários , Idoso , Doadores de Sangue/estatística & dados numéricos , Feminino , Humanos , Procedimentos de Redução de Leucócitos/métodos , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Controle de Qualidade , Estudos Retrospectivos , Fatores Sexuais , Adulto Jovem
20.
Transfusion ; 61(2): 464-473, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33186486

RESUMO

BACKGROUND: Recently, plateletpheresis donations using a widely used leukoreduction system (LRS) chamber have been associated with T-cell lymphopenia. However, clinical health consequences of plateletpheresis-associated lymphopenia are still unknown. STUDY DESIGN AND METHODS: A nationwide cohort study using the SCANDAT3-S database was conducted with all platelet- and plasmapheresis donors in Sweden between 1996 and 2017. A Cox proportional hazards model, using donations as time-dependent exposures, was used to assess the risk of infections associated with plateletpheresis donations using an LRS chamber. RESULTS: A total of 74 408 apheresis donors were included. Among donors with the same donation frequency, plateletpheresis donors using an LRS chamber were at an increased risk of immunosuppression-related infections and common bacterial infections in a dose-dependent manner. While very frequent donors and infections were rare in absolute terms resulting in wide confidence intervals (CIs), the increased risk was significant starting at one-third or less of the allowed donation frequency in a 10-year exposure window, with hazard ratios reaching 10 or more. No plateletpheresis donors that used an LRS chamber experienced a Pneumocystis jirovecii, aspergillus, disseminated mycobacterial, or cryptococcal infection. In a subcohort (n = 42), donations with LRS were associated with low CD4+ T-cell counts (Pearson's R = -0.41; 95% CI, - 0.63 to -0.12). CONCLUSION: Frequent plateletpheresis donation using an LRS chamber was associated with CD4+ T-cell lymphopenia and an increased risk of infections. These findings suggest a need to monitor T-lymphocyte counts in frequent platelet donors and to conduct future investigations of long-term donor health and for regulators to consider steps to mitigate lymphodepletion in donors.


Assuntos
Doadores de Sangue , Infecções/epidemiologia , Procedimentos de Redução de Leucócitos/instrumentação , Linfopenia/etiologia , Plaquetoferese/efeitos adversos , Adulto , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/etiologia , Doadores de Sangue/estatística & dados numéricos , Bases de Dados Factuais , Suscetibilidade a Doenças , Feminino , Seguimentos , Humanos , Hospedeiro Imunocomprometido , Infecções/etiologia , Contagem de Linfócitos , Linfopenia/epidemiologia , Masculino , Pessoa de Meia-Idade , Micoses/epidemiologia , Micoses/etiologia , Plaquetoferese/instrumentação , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Risco , Suécia/epidemiologia , Adulto Jovem
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