Inflammatory markers and auto-Abs to type I IFNs in COVID-19 convalescent plasma cohort study.

Background: COVID-19 convalescent plasma (CCP) contains neutralising anti-SARS-CoV-2 antibodies that may be useful as COVID-19 passive immunotherapy in patients at risk of developing severe disease. Such plasma from convalescent patients may also have additional immune-modulatory properties when transfused to COVID-19 patients.

Methods: CCP (n = 766) was compared to non-convalescent control plasma (n = 166) for soluble inflammatory markers, ex-vivo inflammatory bioactivity on endothelial cells, neutralising auto-Abs to type I IFNs and reported adverse events in the recipients.

Inflammatory profile of convalescent plasma to treat COVID: Impact of amotosalen/UVA pathogen reduction technology.

Blood products in therapeutic transfusion are now commonly acknowledged to contain biologically active constituents during the processes of preparation. In the midst of a worldwide COVID-19 pandemic, preliminary evidence suggests that convalescent plasma may lessen the severity of COVID-19 if administered early in the disease, particularly in patients with profound B-cell lymphopenia and prolonged COVID-19 symptoms. This study examined the influence of photochemical Pathogen Reduction Treatment (PRT) using amotosalen-HCl and UVA light in comparison with untreated control convalescent plasma (n= 72 - paired samples) - cFFP, regarding soluble inflammatory factors: sCD40L, IFN-alpha, IFN-beta, IFN-gamma, IL-1 beta, IL-6, IL-8, IL-10, IL-18, TNF-alpha and inflammatory bioactivity on endothelial cells.

Soluble CD40L and CD62P levels differ in single-donor apheresis platelet concentrates and buffy coat-derived pooled platelet concentrates.

Background: Platelet storage lesions are structural and biochemical changes in platelet concentrates (PCs), and depend on variables in collection and processing, as well as secondary procedures and storage conditions; such lesions can be mitigated by the use of platelet additive solutions (PASs).

Study Design And Methods: This study investigated release of the inflammatory markers sCD40L and sCD62P by single-donor apheresis platelet concentrates (SDA-PCs) and buffy coat-derived pooled platelet concentrates (PPCs) before and after storage. SDA-PC and PPC samples (n = 9089) processed by various methods and stored for different durations were obtained following production in one regional setting, the French National Blood Service.

Assessment of soluble platelet CD40L and CD62P during the preparation process and the storage of apheresis platelet concentrates: Absence of factors related to donors and donations.

Platelet transfusions may be associated with certain adverse effects in recipients, potentially caused by the presence of biological response modifiers contained in the platelet concentrates. The aim of this study is to identify the parameters that reflect platelet activation during both the preparation process and the storage of platelet concentrates. A total of 3,949apheresis platelet concentrate samples were studied with regard to parameters related to the donor as well as to the preparation process and their storage.

Organizing the Donation of Convalescent Plasma for a Therapeutic Clinical Trial on Ebola Virus Disease: The Experience in Guinea.

Although convalescent plasma (CP) transfusion was prioritized among potential Ebola treatments by the World Health Organization, there were concerns on the feasibility of its implementation. We report on the successful organization of donor mobilization and plasma collection as part of the Ebola-Tx clinical trial from November 2014 to July 2015 in Conakry, Guinea. Project implementation registers, tools and reports, mission reports, and minutes of research team meetings were used to reconstruct the sequence of events on how donor mobilization was organized, plasmapheresis was set up, and how effective this approach was in collecting CP.

Improving platelet transfusion safety: biomedical and technical considerations.

Platelet concentrates account for near 10% of all labile blood components but are responsible for more than 25% of the reported adverse events. Besides factors related to patients themselves, who may be particularly at risk of side effects because of their underlying illness, there are aspects of platelet collection and storage that predispose to adverse events. Platelets for transfusion are strongly activated by collection through disposal equipment, which can stress the cells, and by preservation at 22 °C with rotation or rocking, which likewise leads to platelet activation, perhaps more so than storage at 4 °C.

Independent evaluation of tolerance of therapeutic plasma inactivated by amotosalen-HCl-UVA (Intercept ™) over a 5-year period of extensive delivery.

Amotosalen-HCl-UVA (AI) is a process to inactivate pathogens in therapeutic plasma (FFP). Tolerance is the main residual issue in FFP transfusion, and only large series observations are powered enough to identify significantly elevated levels of hazards. We report here on 15,133 new transfusions of AI-FFP, over the previously published 36,035, which in all represents one of the largest series observed by means of a highly standardized surveillance (51.

[Blood transfusion and supply chain management safety].

The level of safety attained in blood transfusion now makes this a discipline better managed care activities. This was achieved both by scientific advances and policy decisions regulating and supervising the activity, as well as by the quality system, which we recall that affects the entire organizational structure, responsibilities, procedures, processes and resources in place to achieve quality management. So, an effective quality system provides a framework within which activities are established, performed in a quality-focused way and continuously monitored to improve outcomes.

Role of Siglec-7 in apoptosis in human platelets.

Background: Platelets participate in tissue repair and innate immune responses. Sialic acid-binding immunoglobulin-like lectins (Siglecs) are well-characterized I-type lectins, which control apoptosis.

Methodology/principal Findings: We characterized the expression of Siglec-7 in human platelets isolated from healthy volunteers using flow cytometry and confocal microscopy.

A computerized prediction model of hazardous inflammatory platelet transfusion outcomes.

Background: Platelet component (PC) transfusion leads occasionally to inflammatory hazards. Certain BRMs that are secreted by the platelets themselves during storage may have some responsibility.

Methodology/principal Findings: First, we identified non-stochastic arrangements of platelet-secreted BRMs in platelet components that led to acute transfusion reactions (ATRs).

[The different types of therapeutic plasma are equivalent?].

In France, three varieties of therapeutic plasma are being processed, distributed and delivered, currently; however, many more varieties are in use worldwide, which go by the property of labile blood component or plasma derived medicines. For one type of component (one given name), several devices and bags and so on are used to concur to its process, which makes that one type of therapeutic plasma may significantly differ from one production setting to one other. This may affect (more or less) the component properties as well as the possibly reported adverse events.

Immune-reactive soluble OX40 ligand, soluble CD40 ligand, and interleukin-27 are simultaneously oversecreted in platelet components associated with acute transfusion reactions.

Background: Leukoreduction of labile blood components dramatically decreases the frequency of minor, intermediate, and severe adverse events (AEs), referred to as acute transfusion reactions (ATRs), especially after transfusion of platelet components (PCs). The pathophysiology of AEs may result from accumulation of soluble, secreted, platelet (PLT) factors with proinflammatory functions stored in PCs. Thus, several cosynergizing factors associated with PLT accumulation in PCs may contribute to clinically reported ATRs with inflammatory symptoms.

A regional haemovigilance retrospective study of four types of therapeutic plasma in a ten-year survey period in France.

Background And Objectives: Our objective was to compare the frequency of adverse events (AEs) due to any of the 4 types of fresh-frozen plasma (FFP) prepared and delivered by the French Blood Establishment (EFS) over a 10-year period. Surveillance of AEs and vigilance was performed according to a homogeneous policy. The four types of FFP comprised of one type (methylene blue [MB) that was stopped since then and of another type [amotosalen (AI)] that was recently introduced, along with two conventional products [quarantine (Q) and solvent-detergent (SD)].

[Pathogen inactivation of platelets: organization consequences for platelet transfusion].

In the past few years, pathogen reduction technologies for labile blood products have been part of the enhancement of global transfusion safety regarding residual risks of transmitting infectious pathogens. Having carried out a feasibility study for the implementation of pathogen inactivation of platelet concentrates by means of the amotosalen/HCl/UVA (Intercept™) technology, and participated to a reinforced haemovigilance study, we took the opportunity to analyze the organization consequences for platelet concentrates inventory and distribution. This impact study first indicated that those novel needs forced the blood donation service, as well as the labile blood product preparation laboratory, to review and improve practices; secondly, it showed that the routine implementation has little (no major) consequence in the overall organization, independently of the economic consequences (not covered here).

[Evaluation of continuous education in transfusion for professionals in medical blood banks].

Purpose Of The Study: Like every actor in transfusion, staff members practising within blood banks of healthcare establishments have to follow a specific initial training and must frequently update their knowledge in blood transfusion.

Methods: To address this need from these professionals, the Établissement français du sang Auvergne-Loire set up training sessions which content regularly evolved according to regulation recommendations. Every cycle consists in a total of 35hours of training, divided in five one-day modules.

In vitro assessment of apheresis and pooled buffy coat platelet components suspended in plasma and SSP+ photochemically treated with amotosalen and UVA for pathogen inactivation (INTERCEPT Blood System™).

Background And Objectives: INTERCEPT Blood System™ is a pathogen inactivation system for blood components. The initial approval required a platelet component to be suspended in a combination of plasma and Platelet additive Solution/PAS-III. Improved platelet storage has been reported with Mg++ and K+ supplementation (PAS-IIIM).

[Analysis of a severe septic transfusion reaction with standard platelet concentrate].

We recently observed a near fatal case of transfusion-transmitted infection with standard platelet concentrate. Streptococcus dysgalactiae subspecies equisimilis was isolated both from donor, residual component container and cultures of the patient's blood. This should question the usefulness of systematic bacterial detection in platelet concentrates, however a lethal accident has occurred recently which escaped bacterial detection.

[Experience with the regionalization of transfusion advice].

We represent an organization of transfusionnel advice at a regional level and we develop arguments and stages having allowed us to lead to this choice. This target was reached in two stages, which took place over 3 years. The regional transfusionnel advice leans on three fundamental points: a planned permanent organization, skilled and formed actors as well as adapted tools.

Donor platelets stored for at least 3 days can elicit activation marker expression by the recipient's blood mononuclear cells: an in vitro study.

Background: Recent studies have demonstrated that infused platelets (PLTs) can promote inflammation. The objective of this study was to evaluate the impact of storage of transfusion-grade PLTs on the peripheral blood mononuclear cells (PBMNCs) of the recipient.

Study Design And Methods: An in vitro cell model system was established to measure the degree of activation of donor PLTs during 5 days of their storage and then to measure immune cell activation by detecting marker expression in coculture experiments.

Direct contact of platelets and their released products exert different effects on human dendritic cell maturation.

Background: Dendritic cells (DCs) are antigen presenting cells capable of inducing innate and adaptive immune responses. According to the stimulus and their maturation state, DCs induce immunogenic or tolerogenic responses. Platelets (PLTs), which are involved in haemostasis and inflammation, can also interact with DCs.

Identification of two subpopulations of purified human blood B cells, CD27- CD23+ and CD27high CD80+, that strongly express cell surface Toll-like receptor 9 and secrete high levels of interleukin-6.

B-cell expression of certain Toll-like receptors (TLRs) is important in linking innate and adaptive immune responses in normal and pathological conditions. The expression of TLR9 plays a role in the recognition of conserved pathogen motifs in a manner that is dependent on B-cell localization, deduced from B-cell phenotype. The nature of TLR9 function is unclear.

Release of immune modulation factors from platelet concentrates during storage after photochemical pathogen inactivation treatment.

Background: Blood platelets (PLTs) are critical for hemostasis, and they contain biologically active constituents with the potential to modulate inflammatory responses. This study examined the effects of photochemical pathogen inactivation treatment (PCT) on the release of cytokines and/or chemokines from PLT components.

Study Design And Methods: Double-dose apheresis PLT components were suspended in plasma-PLT additive solution mixtures and divided into paired therapeutic units.

A flow cytometry technique to study intracellular signals NF-kappaB and STAT3 in peripheral blood mononuclear cells.

Background: Cytokines have essential roles on intercellular communications and are effective in using a variety of intracellular pathways. Among this multitude of signalling pathways, the NF-kappaB (nuclear factor kappaB) and STAT (signal transducer and activator of transcription) families are among the most frequently investigated because of their importance. Indeed, they have important role in innate and adaptive immunity.

Human platelets can activate peripheral blood B cells and increase production of immunoglobulins.

Objective: Blood platelets represent a link between hemostasis, inflammation, and tissue repair. Their role in immune responses and inflammation mainly involves many molecules, among which Toll-like receptor, major histocompatibility complex class I, CD40 and CD154/CD40 ligand (CD40L). As platelets are the major purveyor of soluble CD40L (sCD40L), we sought to determine their involvement in CD40/CD40L-dependent immune responses and to understand the interactions between platelets and peripheral B lymphocytes.