Shared decision-making for patients with vaccine-related concerns of blood transfusion: A single institution experience.

BACKGROUND: Some patients express concerns regarding receipt of allogeneic blood transfusions from donors potentially vaccinated against SARS-CoV-2 (COVID-19). However, limited information exists about patients' expression of these concerns or how to address them during the blood transfusion consent process. In this study, we describe our experience of working collaboratively with patients with vaccine-related transfusion concerns prior to elective surgery, summarizing treatment decisions and clinical outcomes. STUDY DESIGN AND METHODS: This observational descriptive study includes patients seen in our Bloodless Medicine and Surgery clinic between June 2022 and June 2024 for vaccine-related transfusion concerns prior to elective surgery. A shared decision-making framework was employed to foster conversation, share information, provide reassurance, reconcile conflict, and match preferences with available care options. Patient characteristics, treatment decisions, and surgical outcomes were reviewed and summarized. RESULTS: Thirty-five patients were included, with median (1st, 3rd quartile) age of 61 (53, 69) years. Cardiac surgery was the most common type of surgery (29%). Twelve patients (34%) were anemic preoperatively, and all received preoperative treatment. After discussion with a Bloodless Medicine specialist, 24 (68.6%) decided to consent to the use of all blood products, 5 (14.3%) accepted only red blood cells, and 6 (17.1%) declined all blood products. Among 28 patients undergoing surgery, only 4 (14%) received allogeneic transfusion perioperatively. CONCLUSION: Many patients concerned about the vaccination status of blood donors may ultimately consent to allogeneic blood products after shared decision-making with a Bloodless Medicine specialist, highlighting the importance of patient empowerment and collaborative care.

Rates Among Hospitalized Patients With COVID-19 Treated With Convalescent Plasma: A Systematic Review and Meta-Analysis.

Objective: To examine the association of COVID-19 convalescent plasma transfusion with mortality and the differences between subgroups in hospitalized patients with COVID-19. Patients and Methods: On October 26, 2022, a systematic search was performed for clinical studies of COVID-19 convalescent plasma in the literature from January 1, 2020, to October 26, 2022. Randomized clinical trials and matched cohort studies investigating COVID-19 convalescent plasma transfusion compared with standard of care treatment or placebo among hospitalized patients with confirmed COVID-19 were included. The electronic search yielded 3841 unique records, of which 744 were considered for full-text screening. The selection process was performed independently by a panel of 5 reviewers. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data were extracted by 5 independent reviewers in duplicate and pooled using an inverse-variance random effects model. The prespecified end point was all-cause mortality during hospitalization. Results: Thirty-nine randomized clinical trials enrolling 21,529 participants and 70 matched cohort studies enrolling 50,160 participants were included in the systematic review. Separate meta-analyses reported that transfusion of COVID-19 convalescent plasma was associated with a decrease in mortality compared with the control cohort for both randomized clinical trials (odds ratio [OR], 0.87; 95% CI, 0.76-1.00) and matched cohort studies (OR, 0.76; 95% CI, 0.66-0.88). The meta-analysis of subgroups revealed 2 important findings. First, treatment with convalescent plasma containing high antibody levels was associated with a decrease in mortality compared with convalescent plasma containing low antibody levels (OR, 0.85; 95% CI, 0.73 to 0.99). Second, earlier treatment with COVID-19 convalescent plasma was associated with a decrease in mortality compared with the later treatment cohort (OR, 0.63; 95% CI, 0.48 to 0.82). Conclusion: During COVID-19 convalescent plasma use was associated with a 13% reduced risk of mortality, implying a mortality benefit for hospitalized patients with COVID-19, particularly those treated with convalescent plasma containing high antibody levels treated earlier in the disease course.

Demographics of first-time donors returning for donation during the pandemic: COVID-19 convalescent plasma versus standard blood product donors.

BACKGROUND: Previous studies have demonstrated low first-time donor return rates (DRR) following catastrophic events. Little is known, however, about the influence of demographic factors on the DRR of first-time donors during the COVID-19 pandemic, including the unique motivation of COVID-19 convalescent plasma (CCP) donors as compared to non-CCP donors. STUDY DESIGN AND METHODS: Thirteen blood collection organizations submitted deidentified data from first-time CCP and non-CCP donors returning for regular (non-CCP) donations during the pandemic. DRR was calculated as frequencies. Demographic factors associated with returning donors: race/ethnicity, gender, and generation (Gen Z: 19-24, Millennial: 25-40, Gen X: 41-56, and Boomer: ≥57 years old), within the CCP and non-CCP first-time cohorts were compared using chi-square test at p < .05 statistical significance. RESULTS: From March 2020 through December 2021, there were a total of 44,274 first-time CCP and 980,201 first-time non-CCP donors. DRR were 14.6% (range 11.9%-43.3%) and 46.6% (range 10.0%-76.9%) for CCP and non-CCP cohorts, respectively. Age over 40 years (Gen X and Boomers), female gender, and White race were each associated with higher return in both donor cohorts (p < .001). For the non-CCP return donor cohort, the Millennial and Boomers were comparable. CONCLUSION: The findings demonstrate differences in returning donor trends between the two donor cohorts. The motivation of a first-time CCP donor may be different than that of a non-CCP donor. Further study to improve first-time donor engagement would be worthwhile to expand the donor base with a focus on blood donor diversity emphasizing engagement of underrepresented minorities and younger donors.

Coagulation profile of human COVID-19 convalescent plasma.

Convalescent plasma is used to treat COVID-19. There are theoretical concerns about the impact of pro-coagulant factors in convalescent plasma on the coagulation cascade particularly among patients with severe COVID-19. The aim of this study was to evaluate the coagulation profile of COVID-19 convalescent plasma. Clotting times and coagulation factor assays were compared between fresh frozen plasma, COVID-19 convalescent plasma, and pathogen-reduced COVID-19 convalescent plasma. Measurements included prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen, D-dimer, von Willebrand factor activity, von Willebrand factor antigen, coagulation factors II, V, VII-XII, protein S activity, protein C antigen, and alpha-2 plasmin inhibitor. Clotting times and coagulation factor assays were not different between COVID-19 convalescent plasma and fresh frozen plasma, except for protein C antigen. When compared to fresh frozen plasma and regular convalescent plasma, pathogen reduction treatment increased activated partial thromboplastin time and thrombin time, while reducing fibrinogen, coagulation factor II, V, VIII, IX, X, XI, XII, protein S activity, and alpha-2 plasmin inhibitor. The coagulation profiles of human COVID-19 convalescent plasma and standard fresh frozen plasma are not different. Pathogen reduced COVID-19 convalescent plasma is associated with reduction of coagulation factors and a slight prolongation of coagulation times, as anticipated. A key limitation of the study is that the COVID-19 disease course of the convalesced donors was not characterized.

Access to and safety of COVID-19 convalescent plasma in the United States Expanded Access Program: A national registry study.

BACKGROUND: The United States (US) Expanded Access Program (EAP) to coronavirus disease 2019 (COVID-19) convalescent plasma was initiated in response to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. While randomized clinical trials were in various stages of development and enrollment, there was an urgent need for widespread access to potential therapeutic agents. The objective of this study is to report on the demographic, geographical, and chronological characteristics of patients in the EAP, and key safety metrics following transfusion of COVID-19 convalescent plasma. METHODS AND FINDINGS: Mayo Clinic served as the central institutional review board for all participating facilities, and any US physician could participate as a local physician-principal investigator. Eligible patients were hospitalized, were aged 18 years or older, and had-or were at risk of progression to-severe or life-threatening COVID-19; eligible patients were enrolled through the EAP central website. Blood collection facilities rapidly implemented programs to collect convalescent plasma for hospitalized patients with COVID-19. Demographic and clinical characteristics of all enrolled patients in the EAP were summarized. Temporal patterns in access to COVID-19 convalescent plasma were investigated by comparing daily and weekly changes in EAP enrollment in response to changes in infection rate at the state level. Geographical analyses on access to convalescent plasma included assessing EAP enrollment in all national hospital referral regions, as well as assessing enrollment in metropolitan areas and less populated areas that did not have access to COVID-19 clinical trials. From April 3 to August 23, 2020, 105,717 hospitalized patients with severe or life-threatening COVID-19 were enrolled in the EAP. The majority of patients were 60 years of age or older (57.8%), were male (58.4%), and had overweight or obesity (83.8%). There was substantial inclusion of minorities and underserved populations: 46.4% of patients were of a race other than white, and 37.2% of patients were of Hispanic ethnicity. Chronologically and geographically, increases in the number of both enrollments and transfusions in the EAP closely followed confirmed infections across all 50 states. Nearly all national hospital referral regions enrolled and transfused patients in the EAP, including both in metropolitan and in less populated areas. The incidence of serious adverse events was objectively low (<1%), and the overall crude 30-day mortality rate was 25.2% (95% CI, 25.0% to 25.5%). This registry study was limited by the observational and pragmatic study design that did not include a control or comparator group; thus, the data should not be used to infer definitive treatment effects. CONCLUSIONS: These results suggest that the EAP provided widespread access to COVID-19 convalescent plasma in all 50 states, including for underserved racial and ethnic minority populations. The study design of the EAP may serve as a model for future efforts when broad access to a treatment is needed in response to an emerging infectious disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT#: NCT04338360.

Mortality in individuals treated with COVID-19 convalescent plasma varies with the geographic provenance of donors.

Successful therapeutics and vaccines for coronavirus disease 2019 (COVID-19) have harnessed the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Evidence that SARS-CoV-2 exists as locally evolving variants suggests that immunological differences may impact the effectiveness of antibody-based treatments such as convalescent plasma and vaccines. Considering that near-sourced convalescent plasma likely reflects the antigenic composition of local viral strains, we hypothesize that convalescent plasma has a higher efficacy, as defined by death within 30 days of transfusion, when the convalescent plasma donor and treated patient were in close geographic proximity. Results of a series of modeling techniques applied to approximately 28,000 patients from the Expanded Access to Convalescent Plasma program (ClinicalTrials.gov number: NCT04338360) support this hypothesis. This work has implications for the interpretation of clinical studies, the ability to develop effective COVID-19 treatments, and, potentially, for the effectiveness of COVID-19 vaccines as additional locally-evolving variants continue to emerge.

The safety of COVID-19 convalescent plasma donation: A multi-institutional donor hemovigilance study.

BACKGROUND: Although the safety and therapeutic efficacy of COVID-19 convalescent plasma (CCP) has been extensively evaluated, the safety of CCP donation has not been explored in a multi-institutional context. STUDY DESIGN AND METHODS: Nine blood collection organizations (BCOs) participated in a multi-institutional donor hemovigilance effort to assess the safety of CCP donation. Donor adverse events (DAEs) were defined according to the Standard for Surveillance of Complications Related to Blood Donation, and severity was assessed using the severity grading tool. Multivariate analysis was performed to determine attributes associated with DAE severity. RESULTS: The overall DAE rate was 37.7 per 1000 donations. Repeat apheresis and apheresis-naïve donors experienced adverse event rates of 19.9 and 49.8 per 1000 donations, respectively. Female donors contributed 51.9% of CCP donations with a DAE rate of 49.4 per 1000 donations. The DAE rate for male donors was 27.4 per 1000 donations. Vasovagal reactions accounted for over half of all reported DAEs (51.1%). After adjustment, volume of CCP donated was associated with vasovagal reaction severity (odds ratio [OR] 6.5, 95% confidence interval [CI] 2.5-17.1). Donor age and donation history were also associated with DAE severity. Considerable differences in DAE types and rates were observed across the participating BCOs despite the use of standardized hemovigilance definitions. CONCLUSION: The safety of CCP donation appears comparable to that of conventional apheresis plasma donation with similar associated risk factors for DAE types and severity.

Program and patient characteristics for the United States Expanded Access Program to COVID-19 convalescent plasma.

BACKGROUND: The United States (US) Expanded Access Program (EAP) to COVID-19 convalescent plasma was initiated in response to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease-2019 (COVID-19). While randomized clinical trials were in various stages of development and enrollment, there was an urgent need for widespread access to potential therapeutic agents particularly for vulnerable racial and ethnic minority populations who were disproportionately affected by the pandemic. The objective of this study is to report on the demographic, geographic, and chronological access to COVID-19 convalescent plasma in the US via the EAP. METHODS AND FINDINGS: Mayo Clinic served as the central IRB for all participating facilities and any US physician could participate as local physician-principal investigator. Registration occurred through the EAP central website. Blood banks rapidly developed logistics to provide convalescent plasma to hospitalized patients with COVID-19. Demographic and clinical characteristics of all enrolled patients in the EAP were summarized. Temporal trends in access to COVID-19 convalescent plasma were investigated by comparing daily and weekly changes in EAP enrollment in response to changes in infection rate on a state level. Geographical analyses on access to convalescent plasma included assessing EAP enrollment in all national hospital referral regions as well as assessing enrollment in metropolitan and less populated areas which did not have access to COVID-19 clinical trials.From April 3 to August 23, 2020, 105,717 hospitalized patients with severe or life-threatening COVID-19 were enrolled in the EAP. A majority of patients were older than 60 years of age (57.8%), male (58.4%), and overweight or obese (83.8%). There was substantial inclusion of minorities and underserved populations, including 46.4% of patients with a race other than White, and 37.2% of patients were of Hispanic ethnicity. Severe or life-threatening COVID-19 was present in 61.8% of patients and 18.9% of patients were mechanically ventilated at time of convalescent plasma infusion. Chronologically and geographically, increases in enrollment in the EAP closely followed confirmed infections across all 50 states. Nearly all national hospital referral regions enrolled patients in the EAP, including both in metropolitan and less populated areas. CONCLUSIONS: The EAP successfully provided widespread access to COVID-19 convalescent plasma in all 50 states, including for underserved racial and ethnic minority populations. The efficient study design of the EAP may serve as an example framework for future efforts when broad access to a treatment is needed in response to a dynamic disease affecting demographic groups and areas historically underrepresented in clinical studies.

Convalescent Plasma Antibody Levels and the Risk of Death from Covid-19.

BACKGROUND: Convalescent plasma has been widely used to treat coronavirus disease 2019 (Covid-19) under the presumption that such plasma contains potentially therapeutic antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can be passively transferred to the plasma recipient. Whether convalescent plasma with high antibody levels rather than low antibody levels is associated with a lower risk of death is unknown. METHODS: In a retrospective study based on a U.S. national registry, we determined the anti-SARS-CoV-2 IgG antibody levels in convalescent plasma used to treat hospitalized adults with Covid-19. The primary outcome was death within 30 days after plasma transfusion. Patients who were enrolled through July 4, 2020, and for whom data on anti-SARS-CoV-2 antibody levels in plasma transfusions and on 30-day mortality were available were included in the analysis. RESULTS: Of the 3082 patients included in this analysis, death within 30 days after plasma transfusion occurred in 115 of 515 patients (22.3%) in the high-titer group, 549 of 2006 patients (27.4%) in the medium-titer group, and 166 of 561 patients (29.6%) in the low-titer group. The association of anti-SARS-CoV-2 antibody levels with the risk of death from Covid-19 was moderated by mechanical ventilation status. A lower risk of death within 30 days in the high-titer group than in the low-titer group was observed among patients who had not received mechanical ventilation before transfusion (relative risk, 0.66; 95% confidence interval [CI], 0.48 to 0.91), and no effect on the risk of death was observed among patients who had received mechanical ventilation (relative risk, 1.02; 95% CI, 0.78 to 1.32). CONCLUSIONS: Among patients hospitalized with Covid-19 who were not receiving mechanical ventilation, transfusion of plasma with higher anti-SARS-CoV-2 IgG antibody levels was associated with a lower risk of death than transfusion of plasma with lower antibody levels. (Funded by the Department of Health and Human Services and others; ClinicalTrials.gov number, NCT04338360.).

Transition from room temperature to cold-stored platelets for the preservation of blood inventories during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has placed great strain on blood resources. In an effort to extend platelet (PLT) shelf life and minimize waste, our institution transitioned room temperature to cold-stored PLTs for administration to bleeding patients. STUDY DESIGN AND METHODS: We describe the administrative and technical processes involved in transitioning room temperature PLTs to cold storage in April 2020. Additionally, we describe the clinical utilization of cold-stored PLTs in the first month of this practice change, with a focus on changes in PLT counts after transfusion, hemostasis, and safety outcomes. RESULTS: A total of 61 cold-stored PLT units were transfused to 40 bleeding patients, with a median (interquartile range [IQR]) of 1 (1-2) units per patient. The median age was 68 (59-73) years; 58% male. Median pretransfusion and posttransfusion PLTs counts were 88 (67-109) and 115 (93-145). A total of 95% of transfusions were administered in the operating room: 57% cardiac surgery, 20% vascular surgery, 8% general surgery, and 5% solid organ transplantation. Hemostasis was deemed to be adequate in all cases after transfusion. There were no transfusion reactions. One patient (3%) experienced a fever and infection within 5 days of transfusion, which was unrelated to transfusion. Median (IQR) hospital length of stay was 8.5 (6-17) days. Two patients (5%) died in the hospital of complications not related to transfusion. CONCLUSION: Cold-stored PLT utilization was associated with adequate hemostasis and no overt signal for patient harm. Conversion from room temperature to cold-stored PLTs may be one method of reducing waste in times of scarce blood inventories.

Safety Update: COVID-19 Convalescent Plasma in 20,000 Hospitalized Patients.

OBJECTIVE: To provide an update on key safety metrics after transfusion of convalescent plasma in hospitalized coronavirus 2019 (COVID-19) patients, having previously demonstrated safety in 5000 hospitalized patients. PATIENTS AND METHODS: From April 3 to June 2, 2020, the US Food and Drug Administration Expanded Access Program for COVID-19 convalescent plasma transfused a convenience sample of 20,000 hospitalized patients with COVID-19 convalescent plasma. RESULTS: The incidence of all serious adverse events was low; these included transfusion reactions (n=78; <1%), thromboembolic or thrombotic events (n=113; <1%), and cardiac events (n=677, ~3%). Notably, the vast majority of the thromboembolic or thrombotic events (n=75) and cardiac events (n=597) were judged to be unrelated to the plasma transfusion per se. The 7-day mortality rate was 13.0% (12.5%, 13.4%), and was higher among more critically ill patients relative to less ill counterparts, including patients admitted to the intensive care unit versus those not admitted (15.6 vs 9.3%), mechanically ventilated versus not ventilated (18.3% vs 9.9%), and with septic shock or multiple organ dysfunction/failure versus those without dysfunction/failure (21.7% vs 11.5%). CONCLUSION: These updated data provide robust evidence that transfusion of convalescent plasma is safe in hospitalized patients with COVID-19, and support the notion that earlier administration of plasma within the clinical course of COVID-19 is more likely to reduce mortality.

Effect of Convalescent Plasma on Mortality among Hospitalized Patients with COVID-19: Initial Three-Month Experience.

IMPORTANCE: Passive antibody transfer is a longstanding treatment strategy for infectious diseases that involve the respiratory system. In this context, human convalescent plasma has been used to treat coronavirus disease 2019 (COVID-19), but the efficacy remains uncertain. OBJECTIVE: To explore potential signals of efficacy of COVID-19 convalescent plasma. DESIGN: Open-label, Expanded Access Program (EAP) for the treatment of COVID-19 patients with human convalescent plasma. SETTING: Multicenter, including 2,807 acute care facilities in the US and territories. PARTICIPANTS: Adult participants enrolled and transfused under the purview of the US Convalescent Plasma EAP program between April 4 and July 4, 2020 who were hospitalized with (or at risk of) severe or life threatening acute COVID-19 respiratory syndrome. INTERVENTION: Transfusion of at least one unit of human COVID-19 convalescent plasma using standard transfusion guidelines at any time during hospitalization. Convalescent plasma was donated by recently-recovered COVID-19 survivors, and the antibody levels in the units collected were unknown at the time of transfusion. Main Outcomes and Measures: Seven and thirty-day mortality. RESULTS: The 35,322 transfused patients had heterogeneous demographic and clinical characteristics. This cohort included a high proportion of critically-ill patients, with 52.3% in the intensive care unit (ICU) and 27.5% receiving mechanical ventilation at the time of plasma transfusion. The seven-day mortality rate was 8.7% [95% CI 8.3%-9.2%] in patients transfused within 3 days of COVID-19 diagnosis but 11.9% [11.4%-12.2%] in patients transfused 4 or more days after diagnosis (p<0.001). Similar findings were observed in 30-day mortality (21.6% vs. 26.7%, p<0.0001). Importantly, a gradient of mortality was seen in relation to IgG antibody levels in the transfused plasma. For patients who received high IgG plasma (>18.45 S/Co), seven-day mortality was 8.9% (6.8%, 11.7%); for recipients of medium IgG plasma (4.62 to 18.45 S/Co) mortality was 11.6% (10.3%, 13.1%); and for recipients of low IgG plasma (<4.62 S/Co) mortality was 13.7% (11.1%, 16.8%) (p=0.048). This unadjusted dose-response relationship with IgG was also observed in thirty-day mortality (p=0.021). The pooled relative risk of mortality among patients transfused with high antibody level plasma units was 0.65 [0.47-0.92] for 7 days and 0.77 [0.63-0.94] for 30 days compared to low antibody level plasma units. CONCLUSIONS AND RELEVANCE: The relationships between reduced mortality and both earlier time to transfusion and higher antibody levels provide signatures of efficacy for convalescent plasma in the treatment of hospitalized COVID-19 patients. This information may be informative for the treatment of COVID-19 and design of randomized clinical trials involving convalescent plasma. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04338360.

Early Safety Indicators of COVID-19 Convalescent Plasma in 5,000 Patients.

BACKGROUND: Convalescent plasma is the only antibody based therapy currently available for COVID-19 patients. It has robust historical precedence and sound biological plausibility. Although promising, convalescent plasma has not yet been shown to be safe as a treatment for COVID-19. METHODS: Thus, we analyzed key safety metrics after transfusion of ABO-compatible human COVID-19 convalescent plasma in 5,000 hospitalized adults with severe or life threatening COVID-19, with 66% in the intensive care unit, as part of the US FDA Expanded Access Program for COVID-19 convalescent plasma. RESULTS: The incidence of all serious adverse events (SAEs) in the first four hours after transfusion was <1%, including mortality rate (0.3%). Of the 36 reported SAEs, there were 25 reported incidences of related SAEs, including mortality (n=4), transfusion-associated circulatory overload (TACO; n=7), transfusion-related acute lung injury (TRALI; n=11), and severe allergic transfusion reactions (n=3). However, only 2 (of 36) SAEs were judged as definitely related to the convalescent plasma transfusion by the treating physician. The seven-day mortality rate was 14.9%. CONCLUSION: Given the deadly nature of COVID-19 and the large population of critically-ill patients included in these analyses, the mortality rate does not appear excessive. These early indicators suggest that transfusion of convalescent plasma is safe in hospitalized patients with COVID-19.

Early safety indicators of COVID-19 convalescent plasma in 5000 patients.

BACKGROUNDConvalescent plasma is the only antibody-based therapy currently available for patients with coronavirus disease 2019 (COVID-19). It has robust historical precedence and sound biological plausibility. Although promising, convalescent plasma has not yet been shown to be safe as a treatment for COVID-19.METHODSThus, we analyzed key safety metrics after transfusion of ABO-compatible human COVID-19 convalescent plasma in 5000 hospitalized adults with severe or life-threatening COVID-19, with 66% in the intensive care unit, as part of the US FDA expanded access program for COVID-19 convalescent plasma.RESULTSThe incidence of all serious adverse events (SAEs), including mortality rate (0.3%), in the first 4 hours after transfusion was <1%. Of the 36 reported SAEs, there were 25 reported incidences of related SAEs, including mortality (n = 4), transfusion-associated circulatory overload (n = 7), transfusion-related acute lung injury (n = 11), and severe allergic transfusion reactions (n = 3). However, only 2 of 36 SAEs were judged as definitely related to the convalescent plasma transfusion by the treating physician. The 7-day mortality rate was 14.9%.CONCLUSIONGiven the deadly nature of COVID-19 and the large population of critically ill patients included in these analyses, the mortality rate does not appear excessive. These early indicators suggest that transfusion of convalescent plasma is safe in hospitalized patients with COVID-19.TRIAL REGISTRATIONClinicalTrials.gov NCT04338360.FUNDINGMayo Clinic, Biomedical Advanced Research and Development Authority (75A50120C00096), National Center for Advancing Translational Sciences (UL1TR002377), National Heart, Lung, and Blood Institute (5R35HL139854 and R01 HL059842), National Institute of Diabetes and Digestive and Kidney Diseases (5T32DK07352), Natural Sciences and Engineering Research Council of Canada (PDF-532926-2019), National Institute of Allergy and Infectious Disease (R21 AI145356, R21 AI152318, and AI152078), Schwab Charitable Fund, United Health Group, National Basketball Association, Millennium Pharmaceuticals, and Octapharma USA Inc.

Deployment of convalescent plasma for the prevention and treatment of COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), has spurred a global health crisis. To date, there are no proven options for prophylaxis for those who have been exposed to SARS-CoV-2, nor therapy for those who develop COVID-19. Immune (i.e., "convalescent") plasma refers to plasma that is collected from individuals following resolution of infection and development of antibodies. Passive antibody administration through transfusion of convalescent plasma may offer the only short-term strategy for conferring immediate immunity to susceptible individuals. There are numerous examples in which convalescent plasma has been used successfully as postexposure prophylaxis and/or treatment of infectious diseases, including other outbreaks of coronaviruses (e.g., SARS-1, Middle East respiratory syndrome [MERS]). Convalescent plasma has also been used in the COVID-19 pandemic; limited data from China suggest clinical benefit, including radiological resolution, reduction in viral loads, and improved survival. Globally, blood centers have robust infrastructure for undertaking collections and constructing inventories of convalescent plasma to meet the growing demand. Nonetheless, there are nuanced challenges, both regulatory and logistical, spanning donor eligibility, donor recruitment, collections, and transfusion itself. Data from rigorously controlled clinical trials of convalescent plasma are also few, underscoring the need to evaluate its use objectively for a range of indications (e.g., prevention vs. treatment) and patient populations (e.g., age, comorbid disease). We provide an overview of convalescent plasma, including evidence of benefit, regulatory considerations, logistical work flow, and proposed clinical trials, as scale-up is brought underway to mobilize this critical resource.

Point-of-care washing of allogeneic red blood cells for the prevention of transfusion-related respiratory complications (WAR-PRC): a protocol for a multicenter randomised clinical trial in patients undergoing cardiac surgery.

INTRODUCTION: The transfusion-related respiratory complications, transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO), are leading causes of transfusion-related morbidity and mortality. At present, there are no effective preventive strategies with red blood cell (RBC) transfusion. Although mechanisms remain incompletely defined, soluble biological response modifiers (BRMs) within the RBC storage solution may play an important role. Point-of-care (POC) washing of allogeneic RBCs may remove these BRMs, thereby mitigating their impact on post-transfusion respiratory complications. METHODS AND ANALYSIS: This is a multicenter randomised clinical trial of standard allogeneic versus washed allogeneic RBC transfusion for adult patients undergoing cardiac surgery testing the hypothesis that POC RBC washing is feasible, safe, and efficacious and will reduce recipient immune and physiologic responses associated with transfusion-related respiratory complications. Relevant clinical outcomes will also be assessed. This investigation will enrol 170 patients at two hospitals in the USA. Simon's two-stage design will be used to assess the feasibility of POC RBC washing. The primary safety outcomes will be assessed using Wilcoxon Rank-Sum tests for continuous variables and Pearson chi-square test for categorical variables. Standard mixed modelling practices will be employed to test for changes in biomarkers of lung injury following transfusion. Linear regression will assess relationships between randomised group and post-transfusion physiologic measures. ETHICS AND DISSEMINATION: Safety oversight will be conducted under the direction of an independent Data and Safety Monitoring Board (DSMB). Approval of the protocol was obtained by the DSMB as well as the institutional review boards at each institution prior to enrolling the first study participant. This study aims to provide important information regarding the feasibility of POC washing of allogeneic RBCs and its potential impact on ameliorating post-transfusion respiratory complications. Additionally, it will inform the feasibility and scientific merit of pursuing a more definitive phase II/III clinical trial. REGISTRATION: ClinicalTrials.gov registration number is NCT02094118 (Pre-results).

Outcomes of a Quality Improvement Initiative to Prevent Unnecessary Packed Red Blood Cell Transfusions Among Extremely Low Birth-Weight Neonates.

BACKGROUND: Extremely low birth-weight (ELBW) infants frequently receive packed red blood cell (PRBC) transfusions. Recent studies have shown that more restrictive PRBC transfusion guidelines limit donor exposure and reduce transfusion-related costs without any increase in adverse clinical outcomes. PURPOSE: We developed and implemented an evidence-based PRBC transfusion guideline for ELBW infants treated in our unit and then measured provider adherence to this guideline. METHODS/SEARCH STRATEGY: We performed a retrospective review of all PRBC transfusions given to ELBW infants in 2012 (preguideline) and the first half of 2014 (postguideline). We identified the indication for each transfusion by reviewing physiological/laboratory data and the daily clinical note. We then determine whether each transfusion met criteria according to our new evidence-based guideline. FINDINGS/RESULTS: When extrapolating the newly developed protocol to 2012 data, less than 15% of transfusions among ELBW infants would have met the current evidence-based standard. Conversely, during the first 6 months of 2014, 61% of transfusions were administered in adherence to the guideline (P < 001). Using current cost estimates, this represents a projected cost savings of $31,000 in that 6-month period. IMPLICATIONS FOR PRACTICE: A multidisciplinary approach to improving PRBC transfusion practices results in potentially safer, more cost-effective care for ELBW infants. IMPLICATIONS FOR RESEARCH: Given the frequency, potential harms, and costs associated with PRBC transfusions in ELBW infants, it seems both feasible and important to pursue prospective clinical trials comparing permissive and restrictive approaches to transfusion in this vulnerable population.

Reductions in central venous pressure by lower body negative pressure or blood loss elicit similar hemodynamic responses.

The purpose of this study was to compare hemodynamic and blood analyte responses to reduced central venous pressure (CVP) and pulse pressure (PP) elicited during graded lower body negative pressure (LBNP) to those observed during graded blood loss (BL) in conscious humans. We hypothesized that the stimulus-response relationships of CVP and PP to hemodynamic responses during LBNP would mimic those observed during BL. We assessed CVP, PP, heart rate, mean arterial pressure (MAP), and other hemodynamic markers in 12 men during LBNP and BL. Blood samples were obtained for analysis of catecholamines, hematocrit, hemoglobin, arginine vasopressin, and blood gases. LBNP consisted of 5-min stages at 0, 15, 30, and 45 mmHg of suction. BL consisted of 5 min at baseline and following three stages of 333 ml of hemorrhage (1,000 ml total). Individual r(2) values and linear regression slopes were calculated to determine whether the stimulus (CVP and PP)-hemodynamic response trajectories were similar between protocols. The CVP-MAP trajectory was the only CVP-response slope that was statistically different during LBNP compared with BL (0.93 ± 0.27 vs. 0.13 ± 0.26; P = 0.037). The PP-heart rate trajectory was the only PP-response slope that was statistically different during LBNP compared with BL (-1.85 ± 0.45 vs. -0.46 ± 0.27; P = 0.024). Norepinephrine, hematocrit, and hemoglobin were all lower at termination in the BL protocol compared with LBNP (P < 0.05). Consistent with our hypothesis, LBNP mimics the hemodynamic stimulus-response trajectories observed during BL across a significant range of CVP in humans.