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PURPOSE: In patients with a need for frequent but intermittent apheresis, vascular access can prove challenging. We describe the migration of the use of a Vortex LP dual lumen port (Angiodynamics, Latham, NY) to one Powerflow and one ClearVUE power injectable port (Becton Dickinson, Franklin Lakes, NJ) in a series of patients undergoing intermittent apheresis. MATERIALS AND METHODS: All patients had a need for long-term intermittent apheresis. Eight had double lumen Vortex port (pre) and were exchanged for one Powerflow port and one conventional subcutaneous venous port with 90° needle entry (post) while 12 did not have any port in place and received the same configuration. IRB approval was granted. We recorded the treatment time, flow rate, and tissue plasminogen activator (tPA) use for five treatment sessions after placement. When available, we compared five treatments with the Vortex port and the new configuration. RESULTS: The mean treatment time is reduced with the new configuration (P = 0.0033). The predicted mean treatment time, adjusting for gender, race, BMI and age and accounting for correlations within a patient is 91.18 min pre and 77.96 min post. The flow rate is higher with the new configuration (P < 0.0001). The predicted mean flow rate in mL/min is 61.59 for the Vortex port and 71.89 for the new configuration. tPA use was eliminated in the population converted from Vortex ports and had a 48% reduction when compared to all other configurations in the study. CONCLUSION: The introduction of a novel device configuration of venous access ports for intermittent apheresis resulted in higher flow rates and less total time for treatment. Use of tPA was greatly reduced. These results suggest that the new configuration could result in less expense for the hospital and better throughput in a busy pheresis practice. Clinical trial registration with ClinicalTrials.gov: NCT04846374.
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Eliminación de Componentes Sanguíneos , Humanos , Eliminación de Componentes Sanguíneos/métodos , Masculino , Femenino , Persona de Mediana Edad , Activador de Tejido Plasminógeno/administración & dosificación , Factores de Tiempo , Dispositivos de Acceso Vascular , Anciano , AdultoRESUMEN
INTRODUCTION: Apheresis practices in the United States (US) have not been comprehensively characterized to date. This study aimed to address this gap by evaluating apheresis therapy through a national survey. METHODS: A multi-institutional survey was conducted between April and July 2023. The survey, comprising 54 questions, focused on institutional demographics, procedures, equipment, staffing, training, and impacts of the Coronavirus Disease 2019 (COVID-19) pandemic. Responses from 22 institutions, primarily academic medical centers, were analyzed. RESULTS: Therapeutic plasma exchange (TPE) was the most common procedure, followed by hematopoietic progenitor cell collection (HPC-A) and red blood cell exchange (RCE). CAR-T cell collections were widespread, with some institutions supporting over 30 protocols concurrently. Most sites used the Spectra Optia Apheresis System, were managed by a transfusion medicine service, and employed internal apheresis providers. Insufficient staffing levels, exacerbated by the COVID-19 pandemic, were common and most often addressed using overtime. DISCUSSION: The survey highlighted the ubiquity of TPE, expanding cellular collections and staffing challenges. The role of apheresis in supporting cellular therapy, particularly in newly developing cell and gene therapies and clinical trials, was evident. Staffing issues during the pandemic emphasized the need for innovative recruitment strategies. CONCLUSION: This nationwide survey provides the most comprehensive analysis to date of apheresis practices in large US academic centers.
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Eliminación de Componentes Sanguíneos , COVID-19 , Intercambio Plasmático , Humanos , Estados Unidos , Eliminación de Componentes Sanguíneos/estadística & datos numéricos , Eliminación de Componentes Sanguíneos/métodos , COVID-19/terapia , COVID-19/epidemiología , Intercambio Plasmático/métodos , Intercambio Plasmático/estadística & datos numéricos , Encuestas y Cuestionarios , SARS-CoV-2 , PandemiasRESUMEN
Background: Mortality due to immune-mediated thrombotic thrombocytopenic purpura (iTTP) remains significant. Predicting mortality risk may potentially help individualize treatment. The French Thrombotic Microangiopathy (TMA) Reference Score has not been externally validated in the United States. Recent advances in machine learning technology can help analyze large numbers of variables with complex interactions for the development of prediction models. Objectives: To validate the French TMA Reference Score in the United States Thrombotic Microangiopathy (USTMA) iTTP database and subsequently develop a novel mortality prediction tool, the USTMA TTP Mortality Index. Methods: We analyzed variables available at the time of initial presentation, including demographics, symptoms, and laboratory findings. We developed our model using gradient boosting machine, a machine learning ensemble method based on classification trees, implemented in the R package gbm. Results: In our cohort (n = 419), the French score predicted mortality with an area under the receiver operating characteristic curve of 0.63 (95% CI: 0.50-0.77), sensitivity of 0.35, and specificity of 0.84. Our gradient boosting machine model selected 8 variables to predict acute mortality with a cross-validated area under the receiver operating characteristic curve of 0.77 (95% CI: 0.71-0.82). The 2 cutoffs corresponded to sensitivities of 0.64 and 0.50 and specificities of 0.76 and 0.87, respectively. Conclusion: The USTMA Mortality Index was acceptable for predicting mortality due to acute iTTP in the USTMA registry, but not sensitive enough to rule out death. Identifying patients at high risk of iTTP-related mortality may help individualize care and ultimately improve iTTP survival outcomes. Further studies are needed to provide external validation. Our model is one of many recent examples where machine learning models may show promise in clinical prediction tools in healthcare.
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BACKGROUND: Reducing variation in transfusion practices can prevent unwarranted transfusions, an outcome that improves quality of care and patient safety, while lowering costs and eliminating waste of blood. We developed and assessed a system-wide initiative to reduce variation in red blood cell (RBC) transfusion in terms of both transfusion utilization and the number of units transfused. INTERVENTION DESIGN AND METHODS: Our initiative combined a single-unit default order for RBC transfusion in hemodynamically stable, non-bleeding patients with a "Why Give 2 When 1 Will Do?" Choosing Wisely campaign, while also promoting a restrictive hemoglobin threshold (Hb <7 g/dl). This multimodal intervention was implemented across an academic medical center (AMC) with over 950 beds and 10 community hospitals. RESULTS: Between our baseline (CY 2020) and intervention period (CY 2021), single-unit orders increased from 57% to 70% of all RBC transfusion orders (p < .001). The greatest change in ordering practices was at community hospitals, where single-unit orders increased from 46% to 65% (p < .001). Over the same time period, the system-wide mean (SD) Hb result prior to transfusion fell from 7.3 (0.05) to 7.2 g/dl (0.04) (p < .05). We estimate this effort saved over 4000 units of blood and over $4 million in direct and indirect costs in its first year. DISCUSSION: By combining a single-unit default setting in the RBC order with a restrictive hemoglobin threshold, we significantly reduced variation in ordering practices. This effort demonstrates the value of single-unit policies and "nudges" in system-wide patient blood management initiatives.
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Transfusión de Eritrocitos , Hemoglobinas , Humanos , Hemoglobinas/análisis , Transfusión Sanguínea , Bancos de Sangre , Centros Médicos AcadémicosRESUMEN
Previous work from our group and others has shown that patients with breast cancer can generate a T cell response against specific human epidermal growth factor 2 (HER2) epitopes. In addition, preclinical work has shown that this T cell response can be augmented by Ag-directed mAb therapy. This study evaluated the activity and safety of a combination of dendritic cell (DC) vaccination given with mAb and cytotoxic therapy. We performed a phase I/II study using autologous DCs pulsed with two different HER2 peptides given with trastuzumab and vinorelbine to a study cohort of patients with HER2-overexpressing and a second with HER2 nonoverexpressing metastatic breast cancer. Seventeen patients with HER2-overexpressing and seven with nonoverexpressing disease were treated. Treatment was well tolerated, with one patient removed from therapy because of toxicity and no deaths. Forty-six percent of patients had stable disease after therapy, with 4% achieving a partial response and no complete responses. Immune responses were generated in the majority of patients but did not correlate with clinical response. However, in one patient, who has survived >14 y since treatment in the trial, a robust immune response was demonstrated, with 25% of her T cells specific to one of the peptides in the vaccine at the peak of her response. These data suggest that autologous DC vaccination when given with anti-HER2-directed mAb therapy and vinorelbine is safe and can induce immune responses, including significant T cell clonal expansion, in a subset of patients.
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Neoplasias de la Mama , Neoplasias Mamarias Animales , Humanos , Femenino , Animales , Epítopos/metabolismo , Vinorelbina/metabolismo , Vinorelbina/uso terapéutico , Receptor ErbB-2 , Neoplasias de la Mama/metabolismo , Inmunoterapia , Péptidos/metabolismo , Células Dendríticas , Trastuzumab/uso terapéutico , Trastuzumab/metabolismoRESUMEN
CONTEXT.: Substantial variability between different antibody titration methods has been identified since the development and introduction of the uniform procedure in 2008. OBJECTIVE.: To determine whether more recent methods or techniques decrease interlaboratory and intralaboratory variation measured using proficiency testing. DESIGN.: Proficiency test data for antibody titration between 2014 and 2018 were obtained from the College of American Pathologists. Interlaboratory and intralaboratory variations were compared by analyzing the distribution of titer results by method and phase, comparing the results against the supplier's quality control titer, and by evaluating the distribution of paired titer results when each laboratory received a sample with the same titer twice. RESULTS.: A total of 1337 laboratories participated in the antibody titer proficiency test during the study period. Only 54.1% (5874 of 10 852) of anti-D and 63.4% (3603 of 5680) of anti-A reported responses were within 1 titer of the supplier's intended result. Review of the agreement between laboratories of the same methodology found that 78.4% (3139 of 4004) for anti-A and 89.0% (9655 of 10 852) of laboratory responses for anti-D fell within 1 titer of the mode response. When provided with 2 consecutive samples of the same titer (anti-D titer: 16), 85% (367 of 434) of laboratories using the uniform procedure and 80% (458 of 576) using the other method reported a titer difference of 1 or less. CONCLUSIONS.: Despite advances, interlaboratory and intralaboratory variance for this assay remains high in comparison with the strong reliance on titer results in clinical practice. There needs to be a reevaluation of the role of this test in clinical decision-making.
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Medicina Transfusional , Humanos , Reproducibilidad de los Resultados , Anticuerpos , Laboratorios , Control de CalidadRESUMEN
CONTEXT.: Modern RHD genotyping can be used to determine when patients with serologic weak D phenotypes have RHD gene variants at risk for anti-D alloimmunization. However, serologic testing, RhD interpretations, and laboratory management of these patients are quite variable. OBJECTIVE.: To obtain interlaboratory comparisons of serologic testing, RhD interpretations, Rh immune globulin (RhIG) management, fetomaternal hemorrhage testing, and RHD genotyping for weak D-reactive specimens. DESIGN.: We devised an educational exercise in which 81 transfusion services supporting obstetrics performed tube-method RhD typing on 2 unknown red blood cell challenge specimens identified as (1) maternal and (2) newborn. Both specimens were from the same weak D-reactive donor. The exercise revealed how participants responded to these different clinical situations. RESULTS.: Of reporting laboratories, 14% (11 of 80) obtained discrepant immediate-spin reactions on the 2 specimens. Nine different reporting terms were used to interpret weak D-reactive maternal RhD types to obstetricians. In laboratories obtaining negative maternal immediate-spin reactions, 28% (16 of 57) performed unwarranted antiglobulin testing, sometimes leading to recommendations against giving RhIG. To screen for excess fetomaternal hemorrhage after a weak D-reactive newborn, 47% (34 of 73) of reporting laboratories would have employed a contraindicated fetal rosette test, risking false-negative results and inadequate RhIG coverage. Sixty percent (44 of 73) of laboratories would obtain RHD genotyping in some or all cases. CONCLUSIONS.: For obstetric and neonatal patients with serologic weak D phenotypes, we found several critical problems in transfusion service laboratory practices. We provide recommendations for appropriate testing, consistent immunohematologic terminology, and RHD genotype-guided management of Rh immune globulin therapy and RBC transfusions.
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Transfusión Fetomaterna , Sistema del Grupo Sanguíneo Rh-Hr , Embarazo , Femenino , Humanos , Sistema del Grupo Sanguíneo Rh-Hr/genética , Globulina Inmune rho(D)/uso terapéutico , Globulina Inmune rho(D)/genética , Fenotipo , Genotipo , EritrocitosRESUMEN
Amidst the therapeutic void at the onset of the COVID-19 pandemic, a critical mass of scientific and clinical interest coalesced around COVID-19 convalescent plasma (CCP). To date, the CCP literature has focused largely on safety and efficacy outcomes, but little on implementation outcomes or experience. Expert opinion suggests that if CCP has a role in COVID-19 treatment, it is early in the disease course, and it must deliver a sufficiently high titer of neutralizing antibodies (nAb). Missing in the literature are comprehensive evaluations of how local CCP programs were implemented as part of pandemic preparedness and response, including considerations of the core components and personnel required to meet demand with adequately qualified CCP in a timely and sustained manner. To address this gap, we conducted an evaluation of a local CCP program at a large U.S. academic medical center, the University of North Carolina Medical Center (UNCMC), and patterned our evaluation around the dimensions of the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework to systematically describe key implementation-relevant metrics. We aligned our evaluation with program goals of reaching the target population with severe or critical COVID-19, integrating into the structure of the hospital-wide pandemic response, adapting to shifting landscapes, and sustaining the program over time during a compassionate use expanded access program (EAP) era and a randomized controlled trial (RCT) era. During the EAP era, the UNCMC CCP program was associated with faster CCP infusion after admission compared with contemporaneous affiliate hospitals without a local program: median 29.6 hours (interquartile range, IQR: 21.2-48.1) for the UNCMC CCP program versus 47.6 hours (IQR 32.6-71.6) for affiliate hospitals; (P<0.0001). Sixty-eight of 87 CCP recipients in the EAP (78.2%) received CCP containing the FDA recommended minimum nAb titer of ≥1:160. CCP delivery to hospitalized patients operated with equal efficiency regardless of receiving treatment via a RCT or a compassionate-use mechanism. It was found that in a highly resourced academic medical center, rapid implementation of a local CCP collection, treatment, and clinical trial program could be achieved through re-deployment of highly trained laboratory and clinical personnel. These data provide important pragmatic considerations critical for health systems considering the use of CCP as part of an integrated pandemic response.
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COVID-19 , Humanos , COVID-19/epidemiología , COVID-19/terapia , Centros Médicos Académicos , Plasma , Pandemias , Anticuerpos NeutralizantesRESUMEN
BACKGROUND: Due to the coronavirus disease 2019 (COVID-19) pandemic, the transfusion medicine community has experienced unprecedented blood supply shortages since March 2020. As such, numerous changes to everyday practice have occurred with a specific emphasis on blood conservation. We sought to determine the strategies used to mitigate blood shortages and promote blood conservation during the pandemic. METHODS: An anonymous, 37-question survey was developed using Research Electronic Data Capture and distributed via e-mail to transfusion medicine specialists across the US obtained via publicly available databases. RESULTS: Amongst surveyed [41.1% response rate (51/124 institutions)], 98.0% experienced a product shortage, with the greatest number reporting red blood cell (RBC) shortages (92.0%). This led to 35.3% of institutions altering the composition and/or number of blood product suppliers, including a 100% increase in the number of institutions acquiring blood from organizations that connect hospital transfusion services with blood collection centers (e.g., Blood Buy) compared to before March 2020. Prospective triaging of blood products was the most common blood conservation strategy (68.1%), though 35.4% altered their RBC exchange or transfusion program for patients receiving chronic RBC transfusion/exchange. As a result of these changes, 78.6% of institutions reported that these changes resulted in a reduction in blood product usage, and 38.1% reported a decrease in product wastage. CONCLUSIONS: Most hospitals experienced the effects of the supply shortage, and many of them implemented blood conserving measures. Conservation strategies were associated with decreased blood utilization and waste, and future studies could evaluate whether these changes persist.
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Procedimientos Médicos y Quirúrgicos sin Sangre , COVID-19 , Humanos , Estados Unidos/epidemiología , Pandemias , COVID-19/epidemiología , Estudios Prospectivos , Transfusión Sanguínea , HospitalesRESUMEN
COVID-19 convalescent plasma (CCP) was an early and widely adopted putative therapy for severe COVID-19. Results from randomized control trials and observational studies have failed to demonstrate a clear therapeutic role for CCP for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Underlying these inconclusive findings is a broad heterogeneity in the concentrations of neutralizing antibodies (nAbs) between different CCP donors. We conducted this study to evaluate the effectiveness and safety of nAb titer-defined CCP in adults admitted to an academic referral hospital. Patients positive by a SARS-CoV-2 nucleic acid amplification test and with symptoms for <10 days were eligible. Participants received either CCP with nAb titers of >1:640 (high-titer group) or ≥1:160 to 1:640 (standard-titer group) in addition to standard of care treatments. The primary clinical outcome was time to hospital discharge, with mortality and respiratory support evaluated as secondary outcomes. Adverse events were contrasted by CCP titer. Between 28 August and 4 December 2020, 316 participants were screened, and 55 received CCP, with 14 and 41 receiving high- versus standard-titer CCP, respectively. Time to hospital discharge was shorter among participants receiving high- versus standard-titer CCP, accounting for death as a competing event (hazard ratio, 1.94; 95% confidence interval [CI], 1.05 to 3.58; Gray's P = 0.02). Severe adverse events (SAEs) (≥grade 3) occurred in 4 (29%) and 23 (56%) of participants receiving the high versus standard titer, respectively, by day 28 (risk ratio, 0.51; 95% CI, 0.21 to 1.22; Fisher's P = 0.12). There were no observed treatment-related AEs. (This study has been registered at ClinicalTrials.gov under registration no. NCT04524507). IMPORTANCE In this study, in a high-risk population of patients admitted for COVID-19, we found an earlier time to hospital discharge among participants receiving CCP with nAb titers of >1:640 compared with participants receiving CCP with a lower nAb titer and no CCP-related AEs. The significance of our research is in identifying a dose response of CCP and clinical outcomes based on nAb titer. Although limited by a small study size, these findings support further study of high-nAb-titer CCP defined as >1:640 in the treatment of COVID-19.
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COVID-19 , SARS-CoV-2 , Adulto , Humanos , Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19/terapia , Inmunización Pasiva/métodosRESUMEN
Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is characterized by recurring episodes of thrombotic microangiopathy, causing ischemic organ impairment. Black patients are overrepresented in iTTP cohorts in the United States, but racial disparities in iTTP outcome and response to therapy have not been studied. Using the United States Thrombotic Microangiopathies Consortium iTTP Registry, we evaluated the impact of race on mortality and relapse-free survival (RFS) in confirmed iTTP in the United States from 1995 to 2020. We separately examined the impact of rituximab therapy and presentation with newly diagnosed (de novo) or relapsed iTTP on RFS by race. A total of 645 participants with 1308 iTTP episodes were available for analysis. Acute iTTP mortality did not differ by race. When all episodes of iTTP were included, Black race was associated with shorter RFS (hazard ratio [HR], 1.60; 95% CI, 1.16-2.21); the addition of rituximab to corticosteroids improved RFS in White (HR, 0.37; 95% CI, 0.18-0.73) but not Black patients (HR, 0.96; 95% CI, 0.71-1.31). In de novo iTTP, rituximab delayed relapse, but Black patients had shorter RFS than White patients, regardless of treatment. In relapsed iTTP, rituximab significantly improved RFS in White but not Black patients. Race affects overall relapse risk and response to rituximab in iTTP. Black patients may require closer monitoring, earlier retreatment, and alternative immunosuppression after rituximab treatment. How race, racism, and social determinants of health contribute to the disparity in relapse risk in iTTP deserves further study.
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Púrpura Trombocitopénica Trombótica , Proteína ADAMTS13 , Corticoesteroides , Humanos , Púrpura Trombocitopénica Trombótica/terapia , Recurrencia , Rituximab/uso terapéuticoRESUMEN
BACKGROUND AIMS: This white paper was developed to provide leukapheresis guidance for the collection of mononuclear cells from adult and pediatric patients who are destined for immune effector cell (IEC) therapies for commercial and research applications. Currently, there is considerable variability in leukapheresis processes and limited published information regarding best practices relevant to new cellular therapies, especially IECs. Herein the authors address critical leukapheresis questions in five domains to help guide consistent collection processes and ensure high-quality products. The first four domains are onboarding, pre-collection, collection and post-collection, with protocol feasibility, preparation, care and follow-up of the patient/donor at each step, respectively, and technical considerations during collection. The fifth domain of quality assurance focuses on ensuring product potency, purity, safety and auditing. METHODS: The American Society for Apheresis (ASFA) Clinical Applications Committee (IEC Therapy Subcommittee) was charged by the society's board of directors with working collaboratively with other ASFA committees and organizations, including the Foundation for the Accreditation of Cellular Therapy, Association for the Advancement of Blood and Biotherapies, American Society for Transplantation and Cellular Therapy, National Marrow Donor Program and International Society for Cell & Gene Therapy, to develop guidelines regarding leukapheresis collection of cells destined for the manufacture of IEC therapies. After a review of the literature and discussion with members of the involved committees and various institutions, a draft guidance was created and circulated for comment and revision. RESULTS: Critical aspects of apheresis that could affect the quality and quantity of the leukapheresis product were identified. These areas were then discussed and reviewed. After consensus, the best practice guidelines were proposed and accepted. CONCLUSIONS: In the current era of rapid growth of IEC therapies, it is important to address critical leukapheresis steps to provide high-quality products and more consistent practices and to eliminate redundant efforts.
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Eliminación de Componentes Sanguíneos , Adulto , Eliminación de Componentes Sanguíneos/métodos , Tratamiento Basado en Trasplante de Células y Tejidos , Niño , Consenso , Humanos , Leucaféresis/métodos , Donantes de Tejidos , Estados UnidosRESUMEN
BACKGROUND: Chimeric antigen receptor T (CAR-T) cell successes have encouraged continued clinical study. Apheresis collection of starting material for CAR-T cell therapy product manufacturing is critical but described approaches suggest variability and clinical guidelines are currently lacking. The goal of this study was to gather and assess variability in apheresis collection descriptions in publicly available CAR T-cell therapy clinical trials. STUDY DESIGN: We searched clinicaltrials.gov (a publicly available clinical trial database) for "chimeric antigen receptor T cells" on July 01, 2020 and studies accessed July 30, 2020-August 15, 2020. Data collected included date posted, study characteristics, apheresis mentions (number, location, and context), laboratory parameters and transfusion allowances. Apheresis context was analyzed using a qualitative inductive approach of grounded theory method with open coding. Text was classified into 37 context codes, grouped into 12 categories, and then consolidated into patient, procedure, product, and miscellaneous themes. RESULTS: Apheresis was mentioned 1044 times in 322 (51.9%) of 621 total studies. Laboratory parameters mentioned included white blood cells (100 studies), absolute neutrophil count (220 studies), absolute lymphocyte count (102 studies), CD3+ cell (38 studies), hemoglobin (233 studies, 54 studies specified transfusion allowance), and platelet (269 studies, 48 studies specified transfusion allowance). CONCLUSIONS: Apheresis collection of CAR-T cell products is not well-defined in clinical study descriptions and the context is inconsistent. Laboratory parameters useful for apheresis collection are variably present and do not consistently align with current practices. Further exploration, and clinical guideline development will encourage alignment of apheresis collections for CAR-T cell products.
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Eliminación de Componentes Sanguíneos , Receptores Quiméricos de Antígenos , Eliminación de Componentes Sanguíneos/métodos , Humanos , Inmunoterapia Adoptiva , Recuento de Linfocitos , Linfocitos TRESUMEN
The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has now caused over 2 million deaths worldwide and continues to expand. Currently, much is unknown about functionally neutralizing human antibody responses and durability to SARS-CoV-2 months after infection or the reason for the discrepancy in COVID-19 disease and sex. Using convalescent-phase sera collected from 101 COVID-19-recovered individuals 21 to 212 days after symptom onset with 48 additional longitudinal samples, we measured functionality and durability of serum antibodies. We also evaluated associations of individual demographic and clinical parameters with functional neutralizing antibody responses to COVID-19. We found robust antibody durability out to 6 months, as well as significant positive associations with the magnitude of the neutralizing antibody response and male sex and in individuals with cardiometabolic comorbidities. IMPORTANCE In this study, we found that neutralizing antibody responses in COVID-19-convalescent individuals vary in magnitude but are durable and correlate well with receptor binding domain (RBD) Ig binding antibody levels compared to other SARS-CoV-2 antigen responses. In our cohort, higher neutralizing antibody titers are independently and significantly associated with male sex compared to female sex. We also show for the first time that higher convalescent antibody titers in male donors are associated with increased age and symptom grade. Furthermore, cardiometabolic comorbidities are associated with higher antibody titers independently of sex. Here, we present an in-depth evaluation of serologic, demographic, and clinical correlates of functional antibody responses and durability to SARS-CoV-2 which supports the growing literature on sex discrepancies regarding COVID-19 disease morbidity and mortality, as well as functional neutralizing antibody responses to SARS-CoV-2.
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Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , COVID-19/inmunología , SARS-CoV-2/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Formación de Anticuerpos/inmunología , COVID-19/virología , Estudios de Cohortes , Femenino , Humanos , Inmunización Pasiva/métodos , Masculino , Persona de Mediana Edad , Pandemias/prevención & control , Glicoproteína de la Espiga del Coronavirus/inmunología , Adulto JovenRESUMEN
CONTEXT.: ABO mistransfusions are rare and potentially fatal events. Protocols are required by regulatory agencies to minimize this risk to patients, but how these are applied in the context of massive transfusion protocols (MTPs) is not specifically defined. OBJECTIVE.: To evaluate the approaches used by transfusion services for switching from universally compatible to patient ABO type-specific blood components during massive hemorrhage. DESIGN.: We added 1 supplemental multiple-choice question to address the study objective to the 2019 College of American Pathologists proficiency test J-survey (J-A 2019). We also reviewed the available literature regarding this topic. RESULTS.: A total of 881 laboratories responded to the supplemental question. Approximately 80% (704 of 881) reported a policy for ABO-type switching during an MTP. Policies varied considerably between responding laboratories, but most (384 of 704, 55%) required 2 ABO types to match before switching from universal to recipient-specific blood components. Additional safety measures used in a minority of these protocols included reaction strength criteria (103 of 704, 15%), on-call medical director approval (41 0f 704, 5.8%), universal red cell unit number limits (12 of 704, 1.7%), or the presence of a mixed field (3 of 704, 0.4%). CONCLUSIONS.: This survey reveals that significant heterogeneity exists regarding the available approaches for ABO-type switching during an MTP. Specific expert guidance regarding this issue is very limited, and best practices have not yet been established or rigorously investigated.
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Tipificación y Pruebas Cruzadas Sanguíneas , Transfusión Sanguínea , Transfusión de Componentes Sanguíneos , Hemorragia/etiología , Humanos , Encuestas y CuestionariosRESUMEN
The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has now caused over 2 million deaths worldwide and continues to expand. Currently, much is unknown about functionally neutralizing human antibody responses and durability to SARS-CoV-2. Using convalescent sera collected from 101 COVID-19 recovered individuals 21-212 days after symptom onset with forty-eight additional longitudinal samples, we measured functionality and durability of serum antibodies. We also evaluated associations between individual demographic and clinical parameters with functional neutralizing antibody responses to COVID-19. We found robust antibody durability out to six months, as well as significant positive associations with the magnitude of the neutralizing antibody response and male sex. We also show that SARS-CoV-2 convalescent neutralizing antibodies are higher in individuals with cardio-metabolic comorbidities.