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1.
Transfusion ; 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38660952

RESUMO

BACKGROUND: Despite being the largest racial/ethnic minority group in the United States, Hispanic/Latinos (H/L) are significantly underrepresented among blood donors. A lack of proximal blood donation opportunities may be one factor contributing to these disparities. However, few studies have investigated this possibility. STUDY DESIGN AND METHODS: Proprietary data on mobile blood collections in Maricopa County, Arizona, were gathered for the period of January 01, 2022 to April 30, 2022 and paired with census tract information using ArcGIS. Maricopa County encompasses the city of Phoenix with a total population of approximately 4.5 million people, including 1.5 million H/L residents. Blood drive count was regressed on H/L ethnic density and total population, and model estimates were exponentiated to obtain odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: During the specified period, approximately 27,000 red blood cell units were collected through mobile drives. Consistent with expectations, when controlling for total neighborhood population, each 10% increase in H/L ethnic density lowered the odds of having a blood drive in the corresponding neighborhood by 12% (OR = 0.88, 95% CI (0.83, 0.92), p < .001). DISCUSSION: These findings provide initial evidence of fewer proximal donation opportunities in areas with greater H/L population density which may contribute to H/L underrepresentation in blood donation and the need for more inclusive collection efforts. Improved access to blood collection is modifiable and could help to increase the overall blood supply, enhance the ability to successfully match specific blood antigen needs of an increasingly diverse population, and bring about a more resilient blood system.

2.
Transfusion ; 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38661249

RESUMO

BACKGROUND: The COVID-19 pandemic impacted the US blood supply. We compared blood donor demography and infectious disease prevalence before and during the pandemic using a large multicenter database. METHODS: Data were categorized as "Before COVID-19" (March 2018-February 2020) or "During COVID-19" (March 2020-February 2022). Donor demographics, donation frequency, and infectious marker prevalence of HIV, HBV, and HCV were compared for the two time periods. The odds of a donor testing positive for these infections among the two time periods were calculated using multivariable logistic regression. RESULTS: Our study assessed a total of 26,672,213 donations including 13,430,380 before and 13,241,833 during COVID-19. There were significantly more donations from donors who were female, aged 40 and older, white, and repeat, during COVID-19. Donation frequency comparison quantified the increase in donations from donors who were white, female, older, and repeat during the pandemic. The prevalence of HIV and HCV decreased significantly during COVID-19 compared to before, but not for HBV. For HIV, the adjusted odds of infection during the pandemic did not differ but for HBV, the odds were significantly more likely during the pandemic and were significantly lower for HCV. DISCUSSION: Demographics and infectious disease marker prevalence changed during the COVID-19 pandemic in the United States. Prevalence of each infection in the donor population will continue to be monitored to determine if changes were specific to the pandemic period.

3.
Vox Sang ; 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38516962

RESUMO

BACKGROUND AND OBJECTIVES: Nucleic acid-amplification testing (NAT) is used for screening blood donations/donors for blood-borne viruses. We reviewed global viral NAT characteristics and NAT-yield confirmatory testing used by blood operators. MATERIALS AND METHODS: NAT characteristics and NAT-yield confirmatory testing used during 2019 was surveyed internationally by the International Society of Blood Transfusion Working Party Transfusion-Transmitted Infectious Diseases. Reported characteristics are presented herein. RESULTS: NAT was mainly performed under government mandate. Human immunodeficiency virus (HIV), hepatitis C virus (HCV) and hepatitis B virus (HBV) NAT was performed on all donors and donation types, while selective testing was reported for West Nile virus, hepatitis E virus (HEV), and Zika virus. Individual donation NAT was used for HIV, HCV and HBV by ~50% of responders, while HEV was screened in mini-pools by 83% of responders performing HEV NAT. Confirmatory testing for NAT-yield samples was generally performed by NAT on a sample from the same donation or by NAT and serology on samples from the same donation and a follow-up sample. CONCLUSION: In the last decade, there has been a trend towards use of smaller pool sizes or individual donation NAT. We captured characteristics of NAT internationally in 2019 and provide insights into confirmatory testing approaches used for NAT-yields, potentially benefitting blood operators seeking to implement NAT.

4.
Vox Sang ; 119(4): 315-325, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38390819

RESUMO

BACKGROUND AND OBJECTIVES: Nucleic acid amplification testing (NAT), in blood services context, is used for the detection of viral and parasite nucleic acids to reduce transfusion-transmitted infections. This project reviewed NAT for screening blood donations globally. MATERIALS AND METHODS: A survey on NAT usage, developed by the International Society of Blood Transfusion Working Party on Transfusion-transmitted Infectious Diseases (ISBT WP-TTID), was distributed through ISBT WP-TTID members. Data were analysed using descriptive statistics. RESULTS: Forty-three responses were received from 32 countries. Increased adoption of blood donation viral screening by NAT was observed over the past decade. NAT-positive donations were detected for all viruses tested in 2019 (proportion of donations positive by NAT were 0.0099% for human immunodeficiency virus [HIV], 0.0063% for hepatitis C virus [HCV], 0.0247% for hepatitis B virus [HBV], 0.0323% for hepatitis E virus [HEV], 0.0014% for West Nile virus [WNV] and 0.00005% for Zika virus [ZIKV]). Globally, over 3100 NAT-positive donations were identified as NAT yield or solely by NAT in 2019 and over 22,000 since the introduction of NAT, with HBV accounting for over half. NAT-positivity rate was higher in first-time donors for all viruses tested except WNV. During 2019, a small number of participants performed NAT for parasites (Trypanosoma cruzi, Babesia spp., Plasmodium spp.). CONCLUSION: This survey captures current use of blood donation NAT globally. There has been increased NAT usage over the last decade. It is clear that NAT contributes to improving blood transfusion safety globally; however, there is a need to overcome economic barriers for regions/countries not performing NAT.


Assuntos
Hepatite B , Ácidos Nucleicos , Reação Transfusional , Infecção por Zika virus , Zika virus , Humanos , Doação de Sangue , Doadores de Sangue , Vírus da Hepatite B/genética , Técnicas de Amplificação de Ácido Nucleico , Hepatite B/diagnóstico
5.
Int J Infect Dis ; 141: 106958, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38373648

RESUMO

OBJECTIVES: Hepatitis B virus (HBV) infection remains a global health problem. Risk factors for HBV infection are usually assessed in prevalent rather than incident infections. To identify demographic and behavioral risks associated with incident HBV among South African blood donors. METHODS: A case-control study was performed between November 2014 and January 2018. Cases were blood donors testing positive for HBV DNA with or without hepatitis B surface antigen but negative for antibody to hepatitis B core antigen. Participants completed an audio computer-assisted structured interview on exposures during the previous 6 months. Sex-specific multivariable logistic regression yielded independent associations between risks and HBV infection. RESULTS: 56 females and 37 males with incident HBV were compared to 438 female and 439 male controls, respectively. For females, risk factors were accepting money or goods for sex, using agents to prepare one's anus prior to anal sex, penetrating injury, non-Black race, and lower educational status. Men reporting homosexual or bisexual orientation or sex with other men, previous injury, referral for HBV testing, or lack of medical insurance were at increased risk. For both sexes, having more than two male sexual partners increased risk. CONCLUSIONS: Sexual behaviors predominated over parenteral exposures as risks for incident HBV in both female and male blood donors.


Assuntos
Vírus da Hepatite B , Hepatite B , Masculino , Humanos , Feminino , Estudos de Casos e Controles , Doadores de Sangue , África do Sul/epidemiologia , Fatores de Risco , Antígenos de Superfície da Hepatite B , Antígenos do Núcleo do Vírus da Hepatite B , Anticorpos Anti-Hepatite B
6.
AJPM Focus ; 3(2): 100186, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38304025

RESUMO

Introduction: Cardiometabolic diseases are associated with greater COVID-19 severity; however, the influences of cardiometabolic health on SARS-CoV-2 infections after vaccination remain unclear. Our objective was to investigate the associations between temporal blood pressure and total cholesterol patterns and incident SARS-CoV-2 infections among those with serologic evidence of vaccination. Methods: In this prospective cohort of blood donors, blood samples were collected in 2020-2021 and assayed for binding antibodies of SARS-CoV-2 nucleocapsid protein antibody seropositivity. We categorized participants into intraindividual pattern subgroups of blood pressure and total cholesterol (persistently, intermittently, or not elevated [systolic blood pressure <130 mmHg, diastolic blood pressure <80 mmHg, total cholesterol <200 mg/dL]) across the study time points. Results: Among 13,930 donors with 39,736 donations representing 1,127,071 person-days, there were 221 incident SARS-CoV-2 infections among those with serologic evidence of vaccination (1.6%). Intermittent hypertension was associated with greater SARS-CoV-2 infections among those with serologic evidence of vaccination risk (adjusted incidence rate ratio=2.07; 95% CI=1.44, 2.96; p<0.01) than among participants with consistent normotension on the basis of a multivariable Poisson regression. Among men, intermittently elevated total cholesterol (adjusted incidence rate ratio=1.90; 95% CI=1.32, 2.74; p<0.01) and higher BMI at baseline (adjusted hazard ratio=1.44; 95% CI=1.07, 1.93; p=0.01; per 10 units) were associated with greater SARS-CoV-2 infections among those with serologic evidence of vaccination probability; these associations were null among women (both p>0.05). Conclusions: Our findings underscore that the benefits of cardiometabolic health, particularly blood pressure, include a lower risk of SARS-CoV-2 infection after vaccination.

7.
Transfusion ; 64(2): 325-333, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38180267

RESUMO

BACKGROUND: HIV, HBV, and HCV infections for ~60% of the US blood supply are monitored by TTIMS with syphilis added in 2020. STUDY DESIGN AND METHODS: Data were compiled from October 2020 to September 2022. Syphilis prevalence was estimated for allogeneic and directed donors who were consensus positive (CP) and the subset of those with confirmed-active infections (AI). Prevalence and incidence were stratified by demographics for two consecutive 1-year periods, starting October 1, 2020 and for both years combined. Incidence was estimated for repeat donors. Associations between syphilis positivity and other infections were evaluated. RESULTS: Among 14.75 million donations, syphilis prevalence was 28.4/100,000 donations and significantly higher during the second year compared to the first year. Overall, syphilis incidence for the two-year period was 10.8/100,000 person-years. The adjusted odds of a CP infection were 1.18 (95% CI: 1.11, 1.26) times higher in the second year compared to the first, and for AI, 1.22 (95% CI: 1.10, 1.35) times higher in year 2. Highest rates occurred among males, first-time, Black, and younger (ages 18-39) donors, and those in the South US Census region. Syphilis CP donors were 64 (95% CI: 46, 89) times more likely to be HIV CP, and AI donors 77 (95% CI: 52, 114) times more likely to be HIV CP than non-CP donors, when controlling for confounders. SUMMARY/CONCLUSIONS: Syphilis prevalence increased over the study period mirroring national trends reported by CDC and is significantly associated with HIV CP.


Assuntos
Infecções por HIV , Sífilis , Masculino , Humanos , Sífilis/epidemiologia , Estudos Soroepidemiológicos , Incidência , Doadores de Sangue , Infecções por HIV/epidemiologia , Prevalência
8.
Vox Sang ; 119(4): 388-401, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38270352

RESUMO

BACKGROUND AND OBJECTIVES: Until recently, gay, bisexual and other men who have sex with men (MSM) were deferred from donating blood for 3-12 months since the last male-to-male sexual contact. This MSM deferral has been discontinued by several high-income countries (HIC) that now perform gender-neutral donor selection. MATERIALS AND METHODS: An international symposium (held on 20-04-2023) gathered experts from seven HICs to (1) discuss how this paradigm shift might affect the mitigation strategies for transfusion-transmitted infections and (2) address the challenges related to gender-neutral donor selection. RESULTS: Most countries employed a similar approach for implementing a gender-neutral donor selection policy: key stakeholders were consulted; the transition was bridged by time-limited deferrals; donor compliance was monitored; and questions or remarks on anal sex and the number and/or type of sexual partners were often added. Many countries have now adopted a gender-neutral approach in which questions on pre- and post-exposure prophylaxis for human immunodeficiency virus (HIV) have been added (or retained, when already in place). Other countries used mitigation strategies, such as plasma quarantine or pathogen reduction technologies for plasma and/or platelets. CONCLUSION: The experience with gender-neutral donor selection has been largely positive among the countries covered herein and seems to be acceptable to stakeholders, donors and staff. The post-implementation surveillance data collected so far appear reassuring with regards to safety, although longer observation periods are necessary. The putative risks associated with HIV antiretrovirals should be further investigated.


Assuntos
Infecções por HIV , Minorias Sexuais e de Gênero , Humanos , Masculino , Feminino , Homossexualidade Masculina , Seleção de Pacientes , Infecções por HIV/epidemiologia , Doadores de Sangue , Comportamento Sexual , Seleção do Doador
9.
Transfusion ; 64(1): 53-67, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38054619

RESUMO

BACKGROUND: The safety of transfusion of SARS-CoV-2 antibodies in high plasma volume blood components to recipients without COVID-19 is not established. We assessed whether transfusion of plasma or platelet products during periods of increasing prevalence of blood donor SARS-CoV-2 infection and vaccination was associated with changes in outcomes in hospitalized patients without COVID-19. METHODS: We conducted a retrospective cohort study of hospitalized adults who received plasma or platelet transfusions at 21 hospitals during pre-COVID-19 (3/1/2018-2/29/2020), COVID-19 pre-vaccine (3/1/2020-2/28/2021), and COVID-19 post-vaccine (3/1/2021-8/31/2022) study periods. We used multivariable logistic regression with generalized estimating equations to adjust for demographics and comorbidities to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Among 21,750 hospitalizations of 18,584 transfusion recipients without COVID-19, there were 697 post-transfusion thrombotic events, and oxygen requirements were increased in 1751 hospitalizations. Intensive care unit length of stay (n = 11,683) was 3 days (interquartile range 1-5), hospital mortality occurred in 3223 (14.8%), and 30-day rehospitalization in 4144 (23.7%). Comparing the pre-COVID, pre-vaccine and post-vaccine study periods, there were no trends in thromboses (OR 0.9 [95% CI 0.8, 1.1]; p = .22) or oxygen requirements (OR 1.0 [95% CI 0.9, 1.1]; p = .41). In parallel, there were no trends across study periods for ICU length of stay (p = .83), adjusted hospital mortality (OR 1.0 [95% CI 0.9-1.0]; p = .36), or 30-day rehospitalization (p = .29). DISCUSSION: Transfusion of plasma and platelet blood components collected during the pre-vaccine and post-vaccine periods of the COVID-19 pandemic was not associated with increased adverse outcomes in transfusion recipients without COVID-19.


Assuntos
Transfusão de Componentes Sanguíneos , Doadores de Sangue , COVID-19 , Transfusão de Plaquetas , Adulto , Humanos , COVID-19/epidemiologia , Oxigênio , Transfusão de Plaquetas/efeitos adversos , Estudos Retrospectivos , Vacinação , Vacinas contra COVID-19 , Transfusão de Componentes Sanguíneos/efeitos adversos , Plasma , Hospitalização
11.
Transfus Med Rev ; 37(3): 150754, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37741792

RESUMO

Pre- and postexposure prophylaxis for human immunodeficiency virus (HIV) are key to reducing the transmission of this virus. Furthermore, low-toxicity, long-acting formulations provide additional clinical benefits, in particular easier adherence to treatment and prevention. However, breakthrough HIV infections can occur despite the use of pre-exposure prophylaxis (PrEP), mainly due to suboptimal adherence or multi-drug resistant HIV strains. Albeit rare, PrEP breakthrough infections have also been reported in fully adherent patients. Should such breakthrough infection occur in an eligible blood donor, PrEP might suppress viremia and delay antibody seroconversion, thereby masking the infection and increasing the risk of transfusion transmission. This possibility has raised concerns in the blood transfusion community but remains little documented. Therefore, a literature search was performed to assess the state of knowledge on the risk of PrEP breakthrough infection, with a particular focus on the risk of HIV entering the blood supply. Evidently, PrEP breakthrough infections are rare, although the risk is not zero. Moreover, a fraction of individuals - including blood donors - do not disclose PrEP use according to various surveys and measurements of HIV PrEP analytes. Additionally, viremia and seroconversion may remain undetectable or close to the limit of detection for a long time after cessation of PrEP, particularly with long-acting antiretrovirals. Therefore, current recommendations to defer donors for at least 3 months after the last dose of oral PrEP or 2 years for long-acting PrEP appear justified, as they safeguard the blood supply and public trust toward the system. These recommendations help to safeguard blood safety and public trust in the blood supply.

12.
Transfusion ; 63(10): 1872-1884, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37642154

RESUMO

BACKGROUND: Individual risk assessment allows donors to be evaluated based on their own behaviors. Study objectives were to assess human immunodeficiency virus (HIV) risk behaviors in men who have sex with men (MSM) and estimate the proportion of the study population who would not be deferred for higher risk HIV sexual behaviors. STUDY DESIGN AND METHODS: Cross-sectional survey and biomarker assessment were conducted in eight U.S. cities. Participants were sexually active MSM interested in blood donation aged 18-39 years, assigned male sex at birth. Participants completed surveys during two study visits to define eligibility, and self-reported sexual and HIV prevention behaviors. Blood was drawn at study visit 1 and tested for HIV and the presence of tenofovir, one of the drugs in oral HIV pre-exposure prophylaxis (PrEP). Associations were assessed between HIV infection status or HIV PrEP use and behaviors, including sex partners, new partners, and anal sex. RESULTS: A total of 1566 MSM completed the visit 1 questionnaire and blood draw and 1197 completed the visit 2 questionnaire. Among 1562 persons without HIV, 789 (50.4%) were not taking PrEP. Of those not taking PrEP, 66.2% reported one sexual partner or no anal sex and 69% reported no new sexual partners or no anal sex with a new partner in the past 3 months. CONCLUSION: The study found that questions were able to identify sexually active, HIV-negative MSM who report lower risk sexual behaviors. About a quarter of enrolled study participants would be potentially eligible blood donors using individual risk assessment questions.

13.
PLoS One ; 18(4): e0284975, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37099490

RESUMO

Naturally occurring antibodies against ABO antigens present in human sera have been shown to neutralize ABO-expressing HIV in vitro. We investigated associations between ABO and RhD blood groups and HIV infection among blood donors from all blood collection centers in eight of South Africa's nine provinces. Whole blood donations collected from first time donors between January 2012 and September 2016 were tested for HIV RNA by nucleic acid testing and HIV antibody using third generation serology assays. ABO and RhD blood types were determined using automated technology. Odds ratios for the association between HIV positivity and ABO and RhD phenotypes were calculated using multivariable logistic regression analysis. We analyzed 515,945 first time blood donors and the overall HIV prevalence was 1.12% (n = 5790). After multivariable adjustment, HIV infection was weakly associated with RhD positive phenotype (OR = 1.15, 95% CI 1.00-1.33) but not with ABO blood group. The observed association with RhD positive phenotype was marginal and likely due to residual confounding by racial group but could serve to generate hypotheses for further studies.


Assuntos
Infecções por HIV , HIV-1 , Humanos , Sistema ABO de Grupos Sanguíneos/genética , Antígenos , Doadores de Sangue , Infecções por HIV/epidemiologia , HIV-1/genética
14.
Transfusion ; 63(5): 1074-1091, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37005871

RESUMO

BACKGROUND: State of the Science (SoS) meetings are used to define and highlight important unanswered scientific questions. The National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health, and the Office of the Assistant Secretary for Health (OASH), Department of Health and Human Services held a virtual SoS in transfusion medicine (TM) symposium. STUDY DESIGN AND METHODS: In advance of the symposium, six multidisciplinary working groups (WG) convened to define research priorities in the areas of: blood donors and the supply, optimizing transfusion outcomes for recipients, emerging infections, mechanistic aspects of components and transfusion, new computational methods in transfusion science, and impact of health disparities on donors and recipients. The overall objective was to identify key basic, translational, and clinical research questions that will help to increase and diversify the volunteer donor pool, ensure safe and effective transfusion strategies for recipients, and identify which blood products from which donors best meet the clinical needs of specific recipient populations. RESULTS: On August 29-30, 2022, over 400 researchers, clinicians, industry experts, government officials, community members, and patient advocates discussed the research priorities presented by each WG. Dialogue focused on the five highest priority research areas identified by each WG and included the rationale, proposed methodological approaches, feasibility, and barriers for success. DISCUSSION: This report summarizes the key ideas and research priorities identified during the NHLBI/OASH SoS in TM symposium. The report highlights major gaps in our current knowledge and provides a road map for TM research.


Assuntos
National Heart, Lung, and Blood Institute (U.S.) , Medicina Transfusional , Estados Unidos , Humanos , Transfusão de Sangue/métodos
15.
Ann Hematol ; 102(5): 1019-1027, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36884065

RESUMO

Chronic kidney disease (CKD) has a significant impact on sickle cell disease (SCD) morbidity and mortality. Early identification of individuals at highest risk of developing CKD may allow therapeutic intervention to prevent worse outcomes. This study aimed to evaluate the prevalence and risk factors for reduced estimated glomerular filtration rate (eGFR) among adults with SCD in Brazil. Participants in the REDS-III multicenter SCD cohort with more severe genotypes aged ≥ 18 years with at least two serum creatinine values were analyzed. The eGFR was calculated using the Jamaica Sickle Cell Cohort Study GFR equation. The eGFR categories were defined according to the K/DOQI. Participants with eGFR ≥ 90 were compared to those with those with eGFR < 90. Among the 870 participants, 647 (74.4%) had eGFR ≥ 90, 211 (24.3%) had eGFR 60 to 89, six (0.7%) had eGFR 30 to 59, and six (0.7%) had ESRD. Male sex (OR: 37.3; 95%CI: 22.4-65.1), higher age (OR: 1.04; 95%CI: 1.02-1.06), higher diastolic blood pressure (OR: 1.03; 95%CI: 1.009-1.06), lower Hb (OR: 0.80; 95%CI: 0.68-0.93), and lower reticulocytes (OR: 0.94; 95%CI: 0.89-0.99) levels were independently associated with eGFR < 90. There was a trend towards higher odds of death in participants with eGFR < 90 (OR: 1.8; 95%CI: 0.95-3.32; p = 0.065). In turn, participants with eGFR < 60 had a 12.2 (95%CI: 2.1-96.9) times higher odds for death when compared to those with eGFR ≥ 60. In this study, eGFR < 90 was observed in one-quarter of adults. Older age, male sex, higher diastolic blood pressure, lower hemoglobin, and lower reticulocyte levels were associated with occurrence of eGFR < 90. Estimated GFR < 60 increased the risk of mortality.


Assuntos
Anemia Falciforme , Insuficiência Renal Crônica , Humanos , Adulto , Masculino , Brasil/epidemiologia , Estudos de Coortes , Taxa de Filtração Glomerular , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/terapia , Creatinina
16.
medRxiv ; 2023 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-36993312

RESUMO

Human genetic variation has enabled the identification of several key regulators of fetal-to-adult hemoglobin switching, including BCL11A, resulting in therapeutic advances. However, despite the progress made, limited further insights have been obtained to provide a fuller accounting of how genetic variation contributes to the global mechanisms of fetal hemoglobin (HbF) gene regulation. Here, we have conducted a multi-ancestry genome-wide association study of 28,279 individuals from several cohorts spanning 5 continents to define the architecture of human genetic variation impacting HbF. We have identified a total of 178 conditionally independent genome-wide significant or suggestive variants across 14 genomic windows. Importantly, these new data enable us to better define the mechanisms by which HbF switching occurs in vivo. We conduct targeted perturbations to define BACH2 as a new genetically-nominated regulator of hemoglobin switching. We define putative causal variants and underlying mechanisms at the well-studied BCL11A and HBS1L-MYB loci, illuminating the complex variant-driven regulation present at these loci. We additionally show how rare large-effect deletions in the HBB locus can interact with polygenic variation to influence HbF levels. Our study paves the way for the next generation of therapies to more effectively induce HbF in sickle cell disease and ß-thalassemia.

17.
Transfusion ; 63(4): 791-797, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36840440

RESUMO

BACKGROUND: Human leukocyte antigen (HLA) alloimmunization can occur after platelet transfusion. These antibodies can complicate future platelet transfusions or organ transplantation. Animal data suggest that Mirasol pathogen reduction treatment (PRT) can prevent alloimmunization after transfusion. STUDY DESIGN AND METHODS: The MIPLATE trial enrolled 330 of a planned 660 participants with hematological malignancies at risk for grade 2 or greater bleeding. The study was halted early for futility after a planned interim analysis. Participants were randomized to receive PRT versus standard control platelets. Serum samples were collected from participants at baseline (pretransfusion), weekly for the first 4 weeks, then at days 42 and 56. HLA antibody levels were determined using a commercial multianalyte bead-based assay. HLA antibody levels were analyzed using low, medium, and high cutoffs based on prior studies. RESULTS: The rate of alloimmunization was low in both arms of the study, particularly at the high HLA antibody cutoff (total of 6 of 277 subjects at risk, or 2.2%). The risk of alloimmunization did not differ between study arms, nor did the risk of immune refractoriness to platelet transfusion. CONCLUSIONS: The data do not support the conclusion that Mirasol exerted a protective effect against alloimmunization after platelet transfusion in the MIPLATE trial.


Assuntos
Plaquetas , Isoanticorpos , Animais , Humanos , Transfusão de Plaquetas/efeitos adversos , Antígenos HLA , Antígenos de Histocompatibilidade Classe I
18.
Adv Skin Wound Care ; 36(2): 98-105, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36662043

RESUMO

OBJECTIVE: To define the prevalence of leg ulcers and identify the clinical and laboratory factors associated with leg ulcers in adult participants. METHODS: The authors conducted a cross-sectional study of 1,109 patients who were 18 years or older with SS or Sß0-thalassemia genotypes from a Brazilian cohort. Investigators assessed the prevalence of factors associated with leg ulcers from 2013 to 2017. RESULTS: The prevalence of leg ulcers was 21%. Increasing age (odds ratio [OR], 1.07; range, 1.06-1.09), male sex (OR, 2.03; range, 1.44-2.87), treatment with chronic transfusion therapy (OR, 1.88; range, 1.15-3.03), higher indirect bilirubin levels (OR, 1.48; range, 1.02-2.16), and low hemoglobin levels (OR, 2.17; range, 1.52-3.11) were associated with leg ulcers. Participants who self-reported as Black (OR, 6.75; range, 2.63-21.32), mixed (OR, 3.91; range, 1.55-12.20), and other/unknown (OR, 3.84; range, 1.04-15.24) were more likely to have leg ulcers compared with those who self-reported as White. CONCLUSIONS: The prevalence of leg ulcers in this Brazilian cohort was higher than the prevalence reported in developed countries. Known factors such as age and male sex were corroborated. The increased bilirubin level and decreased hemoglobin levels among participants with leg ulcers support the hypothesis that hemolysis is correlated with leg ulcer pathogenesis. Self-reported black skin color was an independent predictor of leg ulcers and warrants further study to understand the etiology and implications of this finding.


Assuntos
Anemia Falciforme , Úlcera da Perna , Humanos , Adulto , Masculino , Brasil/epidemiologia , Estudos Transversais , Anemia Falciforme/complicações , Anemia Falciforme/epidemiologia , Úlcera da Perna/etiologia , Úlcera da Perna/complicações , Hemoglobinas , Bilirrubina
19.
Br J Haematol ; 201(2): 343-352, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36602125

RESUMO

Ischaemic stroke is a common complication of sickle cell disease (SCD) and without intervention can affect 11% of children with SCD before the age of 20. Within the Trans-Omics for Precision Medicine (TOPMed), a genome-wide association study (GWAS) of ischaemic stroke was performed on 1333 individuals with SCD from Brazil (178 cases, 1155 controls). Via a novel Cox proportional-hazards analysis, we searched for variants associated with ischaemic stroke occurring at younger ages. Variants at genome-wide significance (p < 5 × 10-8 ) include two near genes previously linked to non-SCD early-onset stroke (<65 years): ADAMTS2 (rs147625068, p = 3.70 × 10-9 ) and CDK18 (rs12144136, p = 2.38 × 10-9 ). Meta-analysis, which included the independent SCD cohorts Walk-PHaSST and PUSH, exhibited consistent association for variants rs1209987 near gene TBC1D32 (p = 3.36 × 10-10 ), rs188599171 near CUX1 (p = 5.89 × 10-11 ), rs77900855 near BTG1 (p = 4.66 × 10-8 ), and rs141674494 near VPS13C (1.68 × 10-9 ). Findings from this study support a multivariant model of early ischaemic stroke risk and possibly a shared genetic architecture between SCD individuals and non-SCD individuals younger than 65 years.


Assuntos
Anemia Falciforme , Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Adolescente , Adulto , Criança , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Proteínas ADAMTS/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Anemia Falciforme/complicações , Anemia Falciforme/genética , Isquemia Encefálica/genética , Brasil/epidemiologia , Estudo de Associação Genômica Ampla , Acidente Vascular Cerebral/genética
20.
J Infect Dis ; 227(5): 696-707, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35687888

RESUMO

BACKGROUND: Except for public health case reports, the incidence of Zika virus (ZIKV), chikungunya virus (CHIKV), and dengue virus (DENV) infection are not available to assess the potential blood transfusion safety threat in Brazil. METHODS: Pools of 6 donation samples (MP6) left over from human immunodeficiency virus, hepatitis B virus, and hepatitis C virus nucleic acid testing were combined to create MP18 pools (3 MP6 pools). Samples were tested using the Grifols triplex ZIKV, CHIKV, and DENV real-time transcription mediated amplification assay to estimate prevalence of RNAemia and incidence, and to compare these results to case reports in São Paulo, Belo Horizonte, Recife, and Rio de Janeiro, from April 2016 through June 2019. RESULTS: ZIKV, CHIKV, and DENV RNAemia were found from donors who donated without overt symptoms of infection that would have led to deferral. The highest RNAemic donation prevalence was 1.2% (95% CI, .8%-1.9%) for DENV in Belo Horizonte in May 2019. Arbovirus infections varied by location and time of year, and were not always aligned with annual arbovirus outbreak seasons in different regions of the country. CONCLUSIONS: Testing donations for arboviruses in Brazil can contribute to public health. Transfusion recipients were likely exposed to ZIKV, CHIKV, and DENV viremic blood components during the study period.


Assuntos
Arbovírus , Febre de Chikungunya , Vírus Chikungunya , Vírus da Dengue , Dengue , Infecção por Zika virus , Zika virus , Humanos , Febre de Chikungunya/epidemiologia , Brasil/epidemiologia , Doadores de Sangue , Incidência
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