Platelet storage in small bags as a model of platelet function in full-sized containers.

Background: Evaluation of additive solutions, storage containers, new collection and storage methods, and other potential modifications is resource intensive, resulting in diversion of platelets away from blood bank inventories and significant time to complete study recruitments. Our goal was to evaluate the feasibility of a small bag for the study of platelet storage, and, by using a standardized respirometry test, separate daily metabolic capacity from observations made in the dynamic storage environment of changing pH, fuels, and end products.

Methods: Single-donor apheresis platelets collected in 100% plasma had small volumes removed to meet secondary processing requirements.

Platelet storage failure-Metformin as causative agent.

Background: Pathogen reduction technology (PRT)-treated apheresis platelets (APs) were returned without platelet swirl and with pH < 6.2. The platelet donor was taking prescription levothyroxine and metformin plus over-the-counter medications and supplements.

In vitro quality parameters of whole blood-derived platelets pooled using two different platelet pooling sets and stored up to 7 days are similar.

Background: Increasing the number of collections of whole blood-derived platelets (WBDP) and lengthening the allowable storage time may alleviate platelet (PLT) shortages. There is a need for new PLT pooling sets that can provide acceptable quality on Day 7 of storage.

Study Design And Methods: This pool-and-split study compared WBDP prepared using the platelet-rich plasma method with the novel IMUGARD WB PLT pooling set and a control pooling set.

Design of VA CoronavirUs Research and Efficacy Studies-1 (VA CURES-1): A double-blind, randomized placebo-controlled trial of COVID-19 convalescent plasma in hospitalized patients with early respiratory compromise.

Background: Effective therapeutics for severe acute respiratory syndrome CoronaVirus-2 (SARS-CoV-2) infection are evolving. Under Emergency Use Authorization, COVID-19 convalescent plasma (CCP) was widely used in individuals hospitalized for COVID-19, but few randomized controlled trials supported its efficacy to limit respiratory failure or death.

Methods: VA CoronavirUs Research and Efficacy Studies-1 (VA CURES-1) was a double-blind, multi-site, placebo-controlled, randomized clinical trial evaluating the efficacy and safety of CCP with conventional therapy in hospitalized Veterans with SARS-CoV-2 infection and early respiratory compromise (requirement for oxygen).

Feasibility evaluation of two novel systems for the automated preparation and extended storage of DMSO cryopreserved platelets.

Background: Manufacturing methods for dimethyl sulfoxide (DMSO)-cryopreserved platelets (CPPs) are manual and labor intensive. Thawing and prepare-for-transfusion steps are in an open system that requires transfusion within 4 h. A fill-and-finish system (CUE) can automate the manufacturing process.

Platelets from blood diversion pouches (DPs) are a suitable alternative for functional, bioenergetic, and metabolomic analyses.

Background: The collection of the first blood flow into a diversion pouch (DP) has become widely adopted in blood donation systems to reduce whole-blood unit contamination from skin bacteria. The strict control of pre-analytical variables, such as blood collection and proper anticoagulant selection, is critical to diminish experimental variability when studying different aspects of platelet biology. We hypothesize that the functional, mitochondrial, and metabolomic profiles of platelets isolated from the DP are not different from the ones isolated from standard venipuncture (VP), thus representing a suitable collection method of platelets for experimental purposes.

COVID-19 convalescent plasma boosts early antibody titer and does not influence the adaptive immune response.

Multiple randomized, controlled clinical trials have yielded discordant results regarding the efficacy of convalescent plasma in outpatients, with some showing an approximately 2-fold reduction in risk and others showing no effect. We quantified binding and neutralizing antibody levels in 492 of the 511 participants from the Clinical Trial of COVID-19 Convalescent Plasma in Outpatients (C3PO) of a single unit of COVID-19 convalescent plasma (CCP) versus saline infusion. In a subset of 70 participants, peripheral blood mononuclear cells were obtained to define the evolution of B and T cell responses through day 30.

Coronavirus Disease 2019 Convalescent Plasma Outpatient Therapy to Prevent Outpatient Hospitalization: A Meta-Analysis of Individual Participant Data From 5 Randomized Trials.

Background: Outpatient monoclonal antibodies are no longer effective and antiviral treatments for coronavirus disease 2019 (COVID-19) disease remain largely unavailable in many countries worldwide. Although treatment with COVID-19 convalescent plasma (CCP) is promising, clinical trials among outpatients have shown mixed results.

Methods: We conducted an individual participant data meta-analysis from outpatient trials to assess the overall risk reduction for all-cause hospitalizations by day 28 in transfused participants.

COVID-19 Convalescent Plasma Outpatient Therapy to Prevent Outpatient Hospitalization: A Meta-analysis of Individual Participant Data From Five Randomized Trials.

Background: Monoclonal antibody and antiviral treatments for COVID-19 disease remain largely unavailable worldwide, and existing monoclonal antibodies may be less active against circulating omicron variants. Although treatment with COVID-19 convalescent plasma (CCP) is promising, randomized clinical trials (RCTs) among outpatients have shown mixed results.

Methods: We conducted an individual participant data meta-analysis from all outpatient CCP RCTs to assess the overall risk reduction for all-cause hospitalizations by day 28 in all participants who had transfusion initiated.

Chronic granulomatous disease and McLeod syndrome: Stem cell transplant and transfusion support in a 2-year-old patient-a case report.

Chronic granulomatous disease (CGD) with McLeod neuroacanthocytosis syndrome (MLS) is a contiguous gene deletion disorder characterized by defective phagocytic function and decreased Kell antigen expression. CGD cure is achieved through hematopoietic stem cell transplant (HSCT) usually in the peri-pubescent years. The presence of MLS makes peri-transfusion support complex, however.

Hormones, age, and sex affect platelet responsiveness in vitro.

Background: Female sex confers a survival advantage following severe injury in the setting of trauma-induced coagulopathy, with female platelets having heightened responsiveness likely due to estrogen. The effects of testosterone on platelet biology are unknown, and platelets express both estradiol and androgen receptors on the plasma membrane. We hypothesize testosterone decreases platelet responses in vitro, and there are baseline differences in platelet function and metabolism stratified by sex/age.

Hyperbaric treatment of platelets extends in vitro storage to 14 days.

Background: Platelets for transfusion have a storage time of 5-7 days at 22°C-24°C, which results in a strain on the supply chain and supply shortages. We describe a novel method to extend platelet storage using xenon (Xe) gas under high pressure and refrigeration.

Study Design And Methods: Apheresis platelets (APU) prepared in 65% platelet additive solution (PAS) were stored under standard conditions (SC) at 20°C-24°C to Day 5.

Evaluation of amotosalen and UVA pathogen-reduced apheresis platelets after 7-day storage.

Background: Amotosalen/UVA pathogen-reduced platelet components (PRPCs) with storage up to 7 days are standard of care in France, Switzerland, and Austria. PRPCs provide effective hemostasis with reduced risk of transfusion-transmitted infections and transfusion-associated graft versus host disease, reduced wastage and improved availability compared with 5-day-stored PCs. This study evaluated the potency of 7-day PRPCs by in vitro characterization and in vivo pharmacokinetic analysis of autologous PCs.

Cryopreservation of rare pediatric red blood cells for support following bone marrow transplant.

Background: A 2-year-old, 10.8 kg male pediatric patient with X-linked chronic granulomatous disease (CGD) with McLeod syndrome (MLS) was scheduled for a hematopoietic stem cell transplant (HSCT). Identification of allogenic red blood cells (RBC) for post-transplant support was unsuccessful prompting the development of a customized method to collect and freeze rare autologous pediatric cells.

Evaluation of Commercially Available High-Throughput SARS-CoV-2 Serologic Assays for Serosurveillance and Related Applications.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serosurveys can estimate cumulative incidence for monitoring epidemics, requiring assessment of serologic assays to inform testing algorithm development and interpretation of results. We conducted a multilaboratory evaluation of 21 commercial high-throughput SARS-CoV-2 serologic assays using blinded panels of 1,000 highly characterized specimens. Assays demonstrated a range of sensitivities (96%-63%), specificities (99%-96%), and precision (intraclass correlation coefficient 0.

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.

Consensus Statement: Hemostasis Trial Outcomes in Cardiac Surgery and Mechanical Support.

Background: Research evaluating hemostatic agents for the treatment of clinically significant bleeding has been hampered by inconsistency and lack of standardized primary clinical trial outcomes. Clinical trials of hemostatic agents in both cardiac surgery and mechanical circulatory support, such as extracorporeal membrane oxygenation and ventricular assist devices, are examples of studies that lack implementation of universally accepted outcomes.

Methods: A subgroup of experts convened by the National Heart, Lung, and Blood Institute and the US Department of Defense developed consensus recommendations for primary outcomes in cardiac surgery and mechanical circulatory support.

Toxic masculinity in red blood cell units? Testosterone therapy in blood donors revisited.

Background: FDA guidelines limit the use of blood from donors taking testosterone replacement therapy (TRT) to red blood cell (RBC) concentrates, whereas plasma and platelets are discarded. The purpose of this study is to bring awareness to above-average free testosterone concentrations in RBC units from TRT donors.

Study Design: We quantified the concentrations of free (bioavailable; pg/ml) and total (protein bound and free; ng/dl) testosterone in plasma (frozen within 24 h) and supernatants from 42-day stored leukocyte-reduced RBC units from 17 TRT male donors and 17 matched controls (no TRT).

Early post-infection treatment of SARS-CoV-2 infected macaques with human convalescent plasma with high neutralizing activity reduces lung inflammation.

Unlabelled: Early in the SARS-CoV-2 pandemic, there was a high level of optimism based on observational studies and small controlled trials that treating hospitalized patients with convalescent plasma from COVID-19 survivors (CCP) would be an important immunotherapy. However, as more data from controlled trials became available, the results became disappointing, with at best moderate evidence of efficacy when CCP with high titers of neutralizing antibodies was used early in infection. To better understand the potential therapeutic efficacy of CCP, and to further validate SARS-CoV-2 infection of macaques as a reliable animal model for testing such strategies, we inoculated 12 adult rhesus macaques with SARS-CoV-2 by intratracheal and intranasal routes.

Early Convalescent Plasma for High-Risk Outpatients with Covid-19.

Background: Early administration of convalescent plasma obtained from blood donors who have recovered from coronavirus disease 2019 (Covid-19) may prevent disease progression in acutely ill, high-risk patients with Covid-19.

Methods: In this randomized, multicenter, single-blind trial, we assigned patients who were being treated in an emergency department for Covid-19 symptoms to receive either one unit of convalescent plasma with a high titer of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or placebo. All the patients were either 50 years of age or older or had one or more risk factors for disease progression.

Progression and Predictors of SARS-CoV-2 Antibody Seroreactivity In US Blood Donors.

The second largest US blood center began testing for antibodies to SARS-CoV-2, the etiologic agent of Coronavirus Disease-2019 (COVID-19) to identify potential COVID-19 Convalescent Plasma (CCP) donors and encourage blood donation. We report the non-vaccine seroprevalence of total immunoglobulin directed against the S1 spike protein of SARS-CoV-2 in our donors. Unique non-CCP donor sera from June 01to December 31, 2020 were tested with the Ortho VITROS Anti-SARS-CoV-2 total immunoglobulin assay (reactive: signal-to-cutoff (S/C) ≥ 1).