A global analysis of the use of immunoglobulin, shortages in supply, and mitigating measures: A survey of hospital providers (a BEST Collaborative study).

BACKGROUND: Immunoglobulin (IG) therapy is widely used to treat primary and secondary immune deficiencies and as immunomodulatory agent for various disorders. There is great concern that shortages of IG may rise, potentially affecting medical treatment options. STUDY DESIGN AND METHODS: An international survey was developed to study how intravenous immunoglobulins (IVIGs) are used and managed within hospitals in case of shortages. Study data were collected and managed using REDCap electronic data capture tools hosted by the Biomedical Excellence for Safer Transfusion (BEST) Collaborative. The survey was directed to hospital pharmacists and blood bank transfusion professionals and disseminated through members of the BEST Collaborative network. RESULTS: Survey respondents from institutions in the USA, Canada, Europe, Japan, and Australia (n = 13) confirmed that the primary specialties utilizing IG are neurology, hematology, and immunology. More than 60% of respondents reported IG supply shortages, but mitigation strategies were not well developed. DISCUSSION: As IG is the leading driver in plasma demand, more studies are needed to understand current and future demand for IG from the clinical perspective. Necessity lies in establishing clinical guidance to address shortages.

Safety and protection of plasma donors: A scoping review and evidence gap map.

BACKGROUND AND OBJECTIVES: As part of a large-scale project to safely increase plasma collection in Europe, the current scoping review identifies the existing evidence (gaps) on adverse events (AEs) and other health effects in plasmapheresis donors, as well as factors that may be associated with such events/effects. MATERIALS AND METHODS: We searched six databases and three registries. Study characteristics (publication type, language, study design, population, outcomes, associated factors, time of assessment, duration of follow-up, number and frequency of donations, convalescent plasma [y/n], setting and location) were synthesized narratively and in an interactive evidence gap map (EGM). RESULTS: Ninety-four research articles and five registrations were identified. Around 90% were observational studies (57 controlled and 33 uncontrolled), and most of them were performed in Europe (55%) or the United States (20%). Factors studied in association with donor health included donor characteristics (e.g., sex, age) (n = 27), cumulative number of donations (n = 21), donation frequency (n = 11), plasma collection device or programme (n = 11), donor status (first time vs. repeat) (n = 10), donation volume per session (n = 8), time in donation programme (n = 3), preventive measures (n = 2) or other (n = 9). CONCLUSION: The current scoping review provides an accessible tool for researchers and policymakers to identify the available evidence (gaps) concerning plasmapheresis donation safety. Controlled prospective studies with long-term donor follow-up are scarce. Furthermore, additional experimental studies comparing the health effects of different donation frequencies are required to inform a safe upper limit for donation frequency.

The efficacy and effectiveness of drinking interventions to reduce vasovagal reactions in blood donors: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Blood establishments strive to ensure the safety and comfort of blood donors while minimizing adverse events. This review aims to assess the efficacy and effectiveness of eating and/or drinking interventions before, during and/or after blood donation in reducing vasovagal reactions (VVRs). MATERIALS AND METHODS: We analysed randomized and non-randomized controlled trials comparing eating and/or drinking interventions to no intervention, placebo or usual practice on (pre-)syncopal VVRs and related symptoms. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach was used to assess the risk of bias and overall certainty of the evidence. RESULTS: Pre-donation water ingestion likely results in reduced on-site VVRs, compared to no water (2 fewer per 100 donors, moderate-certainty evidence). A pre-donation isotonic drink likely results in reduced VVRs, compared to usual practice (2 fewer per 100 donors, moderate-certainty evidence). Pre-donation salt-loaded sweetened lemon water may result in fewer off-site VVRs, compared to sweetened lemon water only (1 fewer per 100 donors, low-certainty evidence). Pre-donation water and a gel cap containing sucrose with 250 mg caffeine may result in fewer blood donor reaction ratings, compared to pre-donation water only (low-certainty evidence). CONCLUSIONS: Pre-donation plain water ingestion or isotonic drink probably results in a large reduction in on-site and off-site VVRs. Pre-donation water ingestion with caffeine consumption or salt supplementation may result in a VVR reduction, compared to water ingestion only. Future large trials are required to increase the certainty of the effect of these and other interventions in the prevention of VVRs.

Implementation of amotosalen plus ultraviolet A-mediated pathogen reduction for all platelet concentrates in France: Impact on the risk of transfusion-transmitted infections.

BACKGROUND AND OBJECTIVES: Pathogen reduction (PR) technology may reduce the risk of transfusion-transmitted infections (TTIs), notably transfusion-transmitted bacterial infection (TTBI) associated with platelet concentrates (PCs). PR (amotosalen/UVA treatment) was implemented for all PCs transfused in France in November 2017. No bacterial detection was in place beforehand. The study aimed to assess the impact of PR PC on TTI and TTBI near-miss occurrences. MATERIALS AND METHODS: TTI and TTBI near-miss occurrences were compared before and after 100% PR implementation. The study period ran from 2013 to 2022. Over 300,000 PCs were transfused yearly. RESULTS: No PC-related transmission of human immunodeficiency virus, hepatitis C virus, hepatitis B virus and human T-cell lymphotropic virus was reported throughout the study period. PC-mediated hepatitis E virus and hepatitis A virus infections occurred irrespective of PR implementation. Mean PC-mediated TTBI occurrence before PR-PC implementation was 3/year (SD: 1; n = 15; 1/92,687 PC between 2013 and 2016) with a fatal outcome in two patients. Since PR implementation, one TTBI has been reported (day 4 PC, Bacillus cereus) (1/1,645,295 PC between 2018 and 2022; p < 0.001). Two PR PC quarantined because of a negative swirling test harboured bacteria: a day 6 PC in 2021 (B. cereus and Staphylococcus epidermidis) and a day 7 PC in 2022 (Staphylococcus aureus). Five similar occurrences with untreated PC were reported between 2013 and 2020. CONCLUSION: Transfusion of 100% PR PC resulted in a steep reduction in TTBI occurrence. TTBI may, however, still occur. Pathogen-reduced PC-related TTI involving non-enveloped viruses occurs as well.

End of selection criteria based on sexual orientation: An international symposium on alternatives to donation deferral.

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

Syphilis testing in blood donors, France, 2007 to 2022.

BackgroundSyphilis in blood donors (BD) has increased in many countries.AimWe aimed to describe trends in syphilis seroposivity in BD in France, to identify risk factors and assess if a non-treponemic test (NTT) could define BD having recovered from syphilis for more than 1 year.MethodsThe analysis covered the period 2007 to 2022 and 45,875,939 donations. Of the 474 BD syphilis-positive in 2022, 429 underwent additional investigations with an NTT. History of syphilis was obtained at the post-donation interview or based on serology results for repeat donors.ResultsUntil 2021, positivity rates remained stable (mean: 1.18/10,000 donations, range: 1.01-1.38). An increased rate was observed in 2022 (1.74/10,000; p = 0.02). Over the whole study period, prevalence was 2.2 times higher in male than in female BD (4.1 times higher in 2022). The proportion of males with an identified risk factor who have sex with men increased from 16.7% in 2007 to 64.9% in 2022. Based on NTT, 79 (18%) of the donors who were seropositive in 2022 were classified as having been infected in the previous year. History of syphilis was available for 30 of them. All had an infection within the previous 3 years. Among seven donors with a syphilis < 12 months before testing, one had an NTT titre ≥ 8, three a titre between 1 and 4, three were negative.ConclusionSyphilis seropositivity increased considerably in BDs in 2022, mostly in males, notably MSM. Available data did not allow appropriate evaluation of the NTT to distinguish recent from past infection.

Guidance on the Use of Convalescent Plasma to Treat Immunocompromised Patients With Coronavirus Disease 2019.

Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) is a safe and effective treatment for COVID-19 in immunocompromised (IC) patients. IC patients have a higher risk of persistent infection, severe disease, and death from COVID-19. Despite the continued clinical use of CCP to treat IC patients, the optimal dose, frequency/schedule, and duration of CCP treatment has yet to be determined, and related best practices guidelines are lacking. A group of individuals with expertise spanning infectious diseases, virology and transfusion medicine was assembled to render an expert opinion statement pertaining to the use of CCP for IC patients. For optimal effect, CCP should be recently and locally collected to match circulating variant. CCP should be considered for the treatment of IC patients with acute and protracted COVID-19; dosage depends on clinical setting (acute vs protracted COVID-19). CCP containing high-titer severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies, retains activity against circulating SARS-CoV-2 variants, which have otherwise rendered monoclonal antibodies ineffective.

Assessment of the soluble proteins HMGB1, CD40L and CD62P during various platelet preparation processes and the storage of platelet concentrates: The BEST collaborative study.

BACKGROUND: Structural and biochemical changes in stored platelets are influenced by collection and processing methods. This international study investigates the effects of platelet (PLT) processing and storage conditions on HMGB1, sCD40L, and sCD62P protein levels in platelet concentrate supernatants (PCs). STUDY DESIGN/METHODS: PC supernatants (n = 3748) were collected by each international centre using identical centrifugation methods (n = 9) and tested centrally using the ELISA/Luminex platform. Apheresis versus the buffy coat (BC-PC) method, plasma storage versus PAS and RT storage versus cold (4°C) were investigated. We focused on PC preparation collecting samples during early (RT: day 1-3; cold: day 1-5) and late (RT: day 4-7; cold: day 7-10) storage time points. RESULTS: HMGB1, sCD40L, and sCD62P concentrations were similar during early storage periods, regardless of storage solution (BC-PC plasma and BC-PC PAS-E) or temperature. During storage and without PAS, sCD40L and CD62P in BC-PC supernatants increased significantly (+33% and +41%, respectively) depending on storage temperature (22 vs. 4°C). However, without PAS-E, levels decreased significantly (-31% and -20%, respectively), depending on storage temperature (22 vs. 4°C). Contrastingly, the processing method appeared to have greater impact on HMGB1 release versus storage duration. These data highlight increases in these parameters during storage and differences between preparation methods and storage temperatures. CONCLUSIONS: The HMGB1 release mechanism/intracellular pathways appear to differ from sCD62P and sCD40L. The extent to which these differences affect patient outcomes, particularly post-transfusion platelet increment and adverse events, warrants further investigation in clinical trials with various therapeutic indications.

Human immunodeficiency virus, hepatitis C virus and hepatitis B virus incidence in blood donors from 2000 to 2020 in France: Trends and lessons from haemovigilance surveillance.

BACKGROUND AND OBJECTIVES: Data from 21 years (2000-2020) of haemovigilance were used to assess human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) incidence rates in repeat blood donors and the occurrence of transfusion-transmitted (TT) viral infections. MATERIALS AND METHODS: Blood donors who converted for HIV, HCV or HBV markers within serial three-year analysis periods were included. Epidemiological and virological data were retrieved from the national epidemiological donor database and were supplemented with information on blood components and the infection status of recipients of the previous negative donation (D.N-1) of donors who seroconverted. RESULTS: Incidence rates declined from 1.27 to 0.35/100,000 person-years for HIV, from 0.59 to 0.19 for HCV and from 1.66 to 0.18 for HBV. Risk factors and lookback for 232 HIV, 90 HCV and 74 HBV seroconversions were investigated. The main risk factor identified at post-donation interview was having sex with men (47.8% of males) for HIV and a sexual risk for HCV (30.6%) and HBV (37.1%). The viral loads and sequences were retrospectively tested in 191 HIV, 74 HCV and 62 HBV D.N-1 archived samples. Six (five HBV and one HIV-1) were positive all low viral loads. Two recipients were infected by red blood cells from two HBV seroconverting donors before the introduction of HBV-nucleic acid testing. CONCLUSION: HIV, HCV and HBV incidence rates in blood donors declined over the two past decades in France. There is a very small risk of a blood component that tests negative entering the blood supply resulting in TT infections, especially after introduction of molecular assays in donor screening.

Evolving deferral criteria for blood donation in France: Plasma donation by men who have sex with men.

BACKGROUND AND OBJECTIVES: Since the advent of AIDS, men who have sex with men (MSM) have often been deferred from blood donation. In France, quarantine plasma donation by MSM donors with the same deferral rules as for other donors was introduced in July 2016 and continued up to March 2022. At this time, MSM-specific deferral criteria were lifted for all blood or plasma donation. The donor deferral, as well as rate of infectious markers in plasma donors who would have been otherwise deferred for MSM activity, was evaluated and compared with those of the other donors during the same time period from June 2016 to March 2022. RESULTS: A total of 8843 MSM donors made 12,250 plasma donation applications. The overall deferral rate was very high (75.2%), mainly due to the absence of apheresis capacity at the donation site. The deferral criteria for sexual risk were present in 12.1% of MSM donors compared with 1.0% in other plasma and blood donors (p < 0.001). Overall, 994 MSM donors made 2880 plasma donations. Of these, one donation was HIV positive (34.7 vs. 0.6/105 donations by other donors, relative risk [RR]: 61.0 [95% confidence interval [CI]: 8.5-437.7]), one was HBV positive (34.7 vs. 4.5/105 , RR: 7.7 [95% CI: 1.1-54.6]) and none were HCV positive (0 vs. 2.4/105 ). Additionally, 21 donations were syphilis positive (729.2 vs. 10.7/105 , RR: 67.9 [95% CI: 44.2-104.4]). A post hoc analysis of eligible MSM donors who were unable to donate plasma due to logistic constraints yielded similar findings. CONCLUSION: Plasma donation by donors who would have been otherwise deferred for MSM activity was associated with both an increased deferral rate for sexual risk and an increased rate of infectious markers, notably syphilis.

Quality assessment and harmonization of laboratories across Europe for multiple SARS-CoV-2 serology assays.

BACKGROUND AND OBJECTIVES: There is a need for conversion of SARS-CoV-2 serology data from different laboratories to a harmonized international unit. We aimed to compare the performance of multiple SARS-CoV-2 antibody serology assays among 25 laboratories across 12 European countries. MATERIALS AND METHODS: To investigate this we have distributed to all participating laboratories a panel of 15 SARS-CoV-2 plasma samples and a single batch of pooled plasma calibrated to the WHO IS 20/136 standard. RESULTS: All assays showed excellent discrimination between SARS-CoV-2 seronegative plasma samples and pre-vaccinated seropositive plasma samples but differed substantially in raw antibody titres. Titres could be harmonized to binding antibody units per millilitre by calibration in relation to a reference reagent. CONCLUSION: The standardization of antibody quantification is of paramount importance to allow interpretation and comparison of serology data reported in clinical trials in order to identify donor cohorts from whom the most effective convalescent plasma can be collected.

Plasma collection and supply in Europe: Proceedings of an International Plasma and Fractionation Association and European Blood Alliance symposium.

At the symposium organized by the International Plasma and Fractionation Association and European Blood Alliance, experts presented their views and experiences showing that the public sector and its blood establishments may strengthen the collection and increase the supply of plasma using the right strategies in plasma donor recruitment, retention and protection, scaling-up collection by increasing the number of donors within improved/new infrastructure, supportive funding, policies and legislation as well as harmonization of clinical guidelines and the collaboration of all stakeholders. Such approaches should contribute to increased plasma collection in Europe to meet patients' needs for plasma-derived medicinal products, notably immunoglobulins and avoid shortages. Overall, presentations and discussions confirmed that European non-profit transfusion institutions are committed to increasing the collection of plasma for fractionation from unpaid donors through dedicated programmes as well as novel strategies and research.

Convalescent plasma therapy for B-cell-depleted patients with protracted COVID-19.

Anti-CD20 monoclonal antibodies are widely used for the treatment of hematological malignancies or autoimmune disease but may be responsible for a secondary humoral deficiency. In the context of COVID-19 infection, this may prevent the elicitation of a specific SARS-CoV-2 antibody response. We report a series of 17 consecutive patients with profound B-cell lymphopenia and prolonged COVID-19 symptoms, negative immunoglobulin G (IgG)-IgM SARS-CoV-2 serology, and positive RNAemia measured by digital polymerase chain reaction who were treated with 4 units of COVID-19 convalescent plasma. Within 48 hours of transfusion, all but 1 patient experienced an improvement of clinical symptoms. The inflammatory syndrome abated within a week. Only 1 patient who needed mechanical ventilation for severe COVID-19 disease died of bacterial pneumonia. SARS-CoV-2 RNAemia decreased to below the sensitivity threshold in all 9 evaluated patients. In 3 patients, virus-specific T-cell responses were analyzed using T-cell enzyme-linked immunospot assay before convalescent plasma transfusion. All showed a maintained SARS-CoV-2 T-cell response and poor cross-response to other coronaviruses. No adverse event was reported. Convalescent plasma with anti-SARS-CoV-2 antibodies appears to be a very promising approach in the context of protracted COVID-19 symptoms in patients unable to mount a specific humoral response to SARS-CoV-2.

Blood donor eligibility criteria for medical conditions: A BEST collaborative study.

BACKGROUND AND OBJECTIVES: Donor eligibility questions and criteria for medical conditions vary between blood centres, suggesting that they are based more on local regulations or experience, rather than on published data, which are limited. As the donor population ages, medical conditions become more common. We assessed donor health assessment criteria at blood centre members of the Biomedical Excellence for Safer Transfusion (BEST) Collaborative. Our aim was to compare eligibility criteria and determine their underlying basis. MATERIALS AND METHODS: A REDCap survey was sent to blood centre participants, based on medical conditions of greatest interest suggested by the Donor Studies Team of the BEST Collaborative. Participants were asked about current donor health assessment questions, deferral criteria and the basis for their deferral policy (donor risk, recipient risk or both) for 20 medical conditions. RESULTS: Complete responses were received from 26 blood donor centres (24 separate responses) representing a combination of hospital-based centres, large regional centres and community/national blood centres in 14 different countries. Most centres specifically ask about heart and lung conditions, whereas fewer than half inquire about kidney, gastrointestinal or neurological conditions. North American blood centres tended to be less restrictive, while regulatory restrictions are more prevalent in Europe. Most participants felt that the criteria were based on regulatory requirements or experience, rather than on published data. CONCLUSION: There is considerable variability in criteria by region. Ideally, criteria would be more evidence-based rather than based on regulatory requirements or experience. Deferral criteria must balance donor and recipient safety and maintain an adequate blood supply.

Research partnerships between blood services and public health authorities: An international, cross-sectional survey.

BACKGROUND AND OBJECTIVES: The COVID-19 pandemic has brought to the fore how blood services can partner with public health (PH) authorities to inform decisions. Yet the scope of partnerships between blood services and PH authorities is inadequately documented. We explored how blood services partner with PH authorities outside the scope of COVID-19. MATERIALS AND METHODS: On 19 January 2022, survey was sent to employees of blood services located throughout the world. Survey questions mainly pertained to partnerships with PH authorities, including how blood specimens are used and collected. RESULTS: Twenty-seven recipients-4 (14.8%) in Africa, 3 (11.1%) in Asia, 9 (33.3%) in Europe, 6 (22.2%) in North America, 2 (7.4%) in Oceania and 3 (11.1%) in South America-completed the survey. Fifteen recipients (55.6%) indicated their blood service was directly or indirectly supervised by PH authorities. Twenty-four recipients (88.9%) indicated currently using or planning to use blood donor data or samples for PH research or pathogen surveillance. A substantial proportion of respondents reported using samples or results from non-routine tests for the surveillance of non-transfusion-transmitted infectious disease pathogens (n = 13 [48.1%]); samples or results of non-routine tests for PH research unrelated to pathogens (n = 10 [37.0%]); donor data for PH research unrelated to pathogens (n = 12 [44.4%]) and donor data for PH research unrelated to transfusion safety (n = 11 [40.7%]). Fourteen (51.9%) had established (or planned to establish) longitudinal cohorts and 19 (70.4%) biobanks. CONCLUSION: The majority of responding blood services were already involved in or planned to be involved in PH research or pathogen surveillance.

The transfusion of non-prophylactically RH-KEL1 antigen-matched red blood cells is feasible in selected myelodysplastic syndrome and acute myeloid leukaemia patients.

BACKGROUND AND OBJECTIVES: Most myelodysplastic syndromes (MDS) patients become red blood cell (RBC) transfusion-dependent. Transfusing MDS patients with prophylactically RH-KEL1 antigen-matched (PAM) RBC units is recommended to avoid RBC allo-immunization. D+C-E-c+e+, D+C-E+c+e- and D+C+E-c-e+ phenotypes are infrequent among French blood donors. To preserve infrequent phenotype RBC units for patients other than MDS, and to manage frequent phenotype RBC unit stocks, we let, for 1 year, higher-risk non-immunized chronically transfused MDS and acute myeloid leukaemia (AML) patients receive RBC transfusions matched only for D. Our objectives were to evaluate the impact of non-PAM transfusions on the transfusion policy (which would be modified in case of RBC allo-immunization) for frequent and infrequent phenotypes patients and to estimate the number of infrequent phenotypes RBC units that could be redistributed to other patients. RESULTS: Ninety patients were enrolled. Thirty-five patients had infrequent phenotypes, nine received only PAM RBC (143 units) and 26 PAM and non-PAM RBC (415 and 532, respectively): none developed allo-immunization. Fifty-five patients had frequent RBC phenotypes, 34 received only PAM RBC (561 units) and three developed antibodies (2 non-RH-KEL1 and one anti-E); 21 received PAM and non-PAM RBC (436 and 109, respectively) and one developed allo-immunization (unknown specificity). Our strategy enabled us to preserve 532 infrequent phenotypes RBC units: 216 D+C-E-c+e+, 33 D+C-E+c+e- and 283 D+C+E-c-e+ units, representing 48.8% of the total number of RBC units received by infrequent phenotypes patients during the study period. CONCLUSION: Allowing the transfusion of non-PAM RBC in selected chronically transfused MDS and AML patients was feasible and enabled to redistribute infrequent phenotypes RBC units to other patients in need.

Reduced neutralizing antibody potency of COVID-19 convalescent vaccinated plasma against SARS-CoV-2 Omicron variant.

BACKGROUND AND OBJECTIVE: The SARS-CoV-2 Omicron variant displays increased infectiveness as well as mutations resulting in reduced neutralizing activity of antibodies acquired after vaccination or infection involving earlier strains. To assess the ability of vaccinated COVID-19 convalescent plasma (CCP-V) collected before November 2021 to seroneutralize Omicron, we compared neutralizing antibody (nAb) titres of 63 samples against Omicron and earlier B.1 (D614G) strains. METHODS AND FINDINGS: Relationship between anti-Omicron titres and IgG anti-S1 levels (binding arbitrary unit: BAU/ml) was studied. Although correlated, anti-Omicron titres were significantly lower than anti-B.1 titres (median = 80 [10-1280] vs. 1280 [160-10,240], p < 0.0001). Omicron nAb titres and IgG anti-S1 levels were correlated (Spearman's rank correlation coefficient = 0.67). Anti-S1 IgG threshold at 7000 BAU/ml may allow to discard CCP-V without anti-Omicron activity (nAb titre <40). Conversely, only those with highest titres (≥160) had systematically anti-S1 IgG levels >7000 BAU/ml. CONCLUSION: A fraction of CCP-V collected before November 2021 retains anti-Omicron seroneutralizing activity that may be selected by quantitative anti-IgG assays, but such assays do not easily allow the identification of 'high-titre' CCP-V. However, collecting plasma from vaccinated donors recently infected with Omicron may be the best option to provide optimal CCP-V for immunocompromised patients infected with this variant.

COVID-19 convalescent plasma: Evolving strategies for serological screening in France.

Quantitation of anti-SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) neutralizing antibodies (Nabs) is a key parameter in determining the effective dose for treatment with COVID-19 convalescent plasma (CCP). Interpretation of results from clinical trials conducted worldwide requires comparison of Nabs titres obtained from different methods. As virus neutralization tests (VNTs) are not standardized scalable or commercially available, strategies based on intensity of ELISA (Enzyme Linked Immunosorbent Assay) or chemiluminescent binding serological tests were implemented to allow comparisons and establish criteria for determining 'high-titres' of anti-SARS-CoV-2 antibodies (Abs). To this end, the FDA (Food and Drug Administration) has proposed criteria to define high-titre plasmas using different serological assays, including the one used in France for the CCP SARS-CoV-2 Abs screening (Euroimmun anti-S1 IgG). A retrospective study revealed that when using the FDA criteria (ELISA signal-to-cut-off [S/C ratio] ≥3.5), 91% of CCP had Nabs titres ≥40 as assessed with an in-house VNT. French strategy to ensure sufficient stocks of CCP of increasing titre has evolved over time. Recently, we improved our strategy by collecting only plasma from vaccinated convalescent donors as we confirmed that the mean IgG antibody level (ELISA S/C ratio) was significantly higher in plasma from vaccinated convalescent donors compared to donations from unvaccinated convalescent donors: 9.31 (CI 95%: 8.46-10.16) versus 3.22 (CI 95%: 3.05-3.39) (p < 0.001).

Early and out-of-hospital use of COVID-19 convalescent plasma: An international assessment of utilization and feasibility.

BACKGROUND AND OBJECTIVES: The use of coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) in the treatment of patients with severe acute respiratory syndrome-2 infection has been controversial. Early administration of CCP before hospital admission offers a potential advantage. This manuscript summarizes current trials of early use of CCP and explores the feasibility of this approach in different countries. MATERIALS AND METHODS: A questionnaire was distributed to the International Society of Blood Transfusion (ISBT) CCP working group. We recorded respondents' input on existing trials on early/outpatient CCP and out-of-hospital (OOH)/home transfusion (HT) practices in their countries and feedback on challenges in initiating home CCP infusion programmes. In addition, details of existing trials registered on clinicaltrials.gov were summarized. RESULTS: A total of 31 country representatives participated. Early/OOH CCP transfusion studies were reported in the United States, the Netherlands, Spain and Brazil. There were a total of six published and five ongoing trials on the prophylactic and therapeutic early use of CCP. HT was practised in Australia, the UK, Belgium, France, Japan, Nigeria, the Netherlands, Spain, Italy, Norway, the United States and some provinces in Canada. Thirty-four representatives indicated a lack of OOH CCP or HT in their institutions and countries. Barriers to implementation of OOH/HT included existing legislation, lack of policies pertaining to outpatient transfusion, and associated logistical challenges, including lack of staffing and resources. CONCLUSION: Early administration of CCP remains a potential option in COVID-19 management in countries with existing OOH/HT programmes. Legislation and regulatory bodies should consider OOH/HT practice for transfusion in future pandemics.

The impact of pathogen-reduced platelets in acute leukaemia treatment on the total blood product requirement: a subgroup analysis of an EFFIPAP randomised trial.

OBJECTIVE: To evaluate the impact of pathogen-reduced (PR) platelet transfusions on blood products requirement for clinical practice. BACKGROUND: PR platelets are increasing in use as standard blood products. However, few randomised trials have evaluated their impact on bleeding control or prevention. Furthermore, PR platelets recirculate less than untreated platelets. METHODS: A subgroup study of the randomised clinical trial EFFIPAP compared three arms of platelet preparations (PR: P-PRP/PAS, additive solution: P-PAS and plasma P-P arms respectively). The subgroup of acute leukaemia patients, in their chemotherapy induction phase, included 392 patients (133 P-PRP/PAS arm, 132 P-PAS arm and 130 P-P arm). Blood requirements were analysed across over periods of 7 days. RESULTS: The number of platelet transfusions per week was significantly higher in the P-PRP/PAS group 2.3 [1.6-3.3] compared to the control groups 1.9 [1.3-2.8] and 2.0 [1.3-3.0] for P-P and P-PAS groups respectively (p < 0.0001). However, the total number of platelets transfused per week was not different. The number of red blood cell concentrates (RBC) transfusion per week did not differ either. CONCLUSION: In a homogeneous group of patients, platelet pathogen reduction resulted in an increased number of platelet units transfused per week while having no impact on the total number of platelets transfused or the number of RBC transfusion; resulting to an average requirement of 2 RBC and 2-3 platelets transfusions per week of marrow aplasia.