Transfusion

BackgroundEnvenoming from numerous sources, such as snakes, scorpions, and spiders, is a major health issue across the world, resulting in millions of cases and tens of thousands of deaths annually. Venom induced symptoms ranges from systemic reactions like nausea and vomiting to localised pain and swelling. One major risk is the development of venom induced consumption coagulopathy (VICC), which might result in significant consequences. Plasmapheresis is being investigated as a possible therapy for severe envenoming. ObjectivesWe aim to assess the effectiveness and potential advantages of plasmapheresis in snakebite cases, focusing on clinical results. We seek to find if plasmapheresis improves neurological, renal, and hematological dysfunction and impacts secondary outcomes, including patient discharge rates, morbidity, mortality, duration of hospital stay, and the number of plasmapheresis sessions required. MethodsFollowing PRISMA guidelines, we conducted a systematic search of articles published between 1980 and July 2023 across multiple databases. MeSH terms related to snakebite and plasmapheresis were applied without publication or language type restrictions. Inclusion criteria considered case reports, cross-sectional studies, or case series featuring plasmapheresis in snakebite management. Inclusions were participants aged 18 years or older with confirmed or suspected snakebites, meeting plasmapheresis indications. Exclusions included participants under 18 years, studies reporting only in vitro data, review articles, and redundant reporting. The emphasis was on Emergency Departments or Intensive Care Units. ResultsIn a review of 147 cases (1980 to July 2023), the most common snake was the hump-nosed viper (Hypnale hypnale). Renal, neurological, and hematological dysfunctions improved after plasmapheresis. The mean plasmapheresis sessions were 2.1, and the average hospital stay was 13.13 days. ConclusionOnce the data has been analyzed, the result emphasizes the clinical importance of plasmapheresis in snakebite envenoming. It helps decision-making when standard therapies are insufficient or ineffective, potentially saving lives. Author SummarySnakebites pose a significant global health threat, causing numerous deaths and serious injuries annually. While antivenom is the primary treatment, its not always effective or available. This study explores an alternative treatment called plasmapheresis, a method that filters harmful substances from the blood. We reviewed 147 cases of snake envenoming treated with plasmapheresis between 1980 and 2023. Our findings show that plasmapheresis can improve various complications caused by snake venom, including kidney problems, nerve damage, and blood disorders. On average, patients received about two plasmapheresis treatments and stayed in the hospital for around 13 days. The study suggests that plasmapheresis could be a valuable option when standard treatments arent working well enough. It might help save lives in severe cases of snake envenoming. While more research is needed, this review provides important insights for doctors treating snakebite victims, especially in areas where snakebites are common and resources are limited.

IntroductionAntivenom neutralizes the effects of snake venom toxins. Its timely administration can by critical in reducing the risk of complications, including serious clinical hemorrhage. The objective of this study was to evaluate the relationship between the late administration of antivenom and the persistence of venom-induced consumption coagulopathy (VICC) in patients with Bothrops snakebite envenomation. MethodsWe conducted a retrospective observational study in three hospitals referent in the management of snakebite envenomation in a region of Colombia. Patients were identified through ICD10 codes. The information was extracted from patients clinical records. Late and early antivenom administration patients were compared; "late" was defined as a period between snakebite and antivenom administration >4h. Definition of persistence of VICC was as an International Normalized Ratio >1.5 between 25-72h after snakebite. The clinical bleeding (as reported by clinicians) was also explored. Groups were compared through X2 of association; binary and multiple logistic regressions were ran to estimate the magnitude of the crude and adjusted relative risk (RR) for the analyzed outcomes. Results304 patients with snakebite from Bothrops spp.were analyzed; 138 (45.3%) with late antivenom administration, and 166 (54.7%) early. The persistence of VICC was more frequent in the late antivenom group (2.06 [95% IC 1.11-3.83]), as well as for clinical bleeding and major bleeding (1.97[1.30-2.98]; 3.00 [1.19-7.54], respectively). DiscussionLate antivenom administration was associated with increased risk in the persistence of VICC and major bleeding in patients with envenomation by a Bothrops complex snakebite. The results reported in the literature are diverse; inter and intra species variability and definitions can influence the finding. ConclusionsThe Timely administration of antivenom was associated with an increased risk in persistence of VICC. SynopsisSnakebites can cause different levels of damage to humans, depending on the type of venom. The venom produced by pit vipers, specifically those of the genus Bothrops, can change blood clotting and cause bleeding that can be life-threatening. Most snakebites from these vipers occur in tropical areas where the most affected are farmers and rural people. There is often a lack of access to antivenom treatment, depending on access to and provision of health services. It seems that giving the antivenom at the right time can reduce the risk of complications. However, it is still unclear whether waiting to give the antivenom increases the risk of continued envenoming and bleeding. This study shows that waiting to treat a patient can lead to a higher chance of bleeding. This information can help doctors, decision makers, and lawmakers improve treatment options and access in remote areas.

BackgroundSnakebite envenoming (SBE) remains a major neglected tropical disease in Sudan. Venom-induced consumption coagulopathy (VICC) is the most frequent and fatal systemic complication, particularly following envenoming by hemotoxic Echis species. Robust clinical data on VICC in Sudan are limited. MethodsWe conducted a prospective hospital-based cohort study at Sinja Teaching Hospital, Sennar state, Sudan, from March to September 2022. All patients admitted with SBE were enrolled. VICC was diagnosed using the 20-minute whole blood clotting test (WBCT20) and laboratory coagulation assays. Clinical features, laboratory abnormalities, management, and outcomes were recorded until discharge or death. ResultsAmong 119 patients with SBE (mean age 34.5 {+/-} 9 years; 79.8% male), VICC developed in 96 (80.7%). Echis spp. were implicated in 86.6% of cases based on patient recognition. Spontaneous systemic bleeding occurred in 88.5% of VICC patients, and life-threatening hemorrhage in 30.2%, most commonly intracerebral hemorrhage. Acute kidney injury occurred in 36.5% of VICC cases. WBCT20 was positive in all VICC patients and showed high diagnostic sensitivity. Despite administration of fresh frozen plasma, mortality among VICC patients was 30.2%. All paediatric patients died. ConclusionsVICC was highly prevalent and associated with severe hemorrhage, acute kidney injury, and high mortality in this snakebite-endemic region of Sudan. Supportive therapy alone was insufficient to prevent fatal outcomes, reflecting delayed presentation and the absence of effective Echis-specific antivenom. Improved access to species-appropriate antivenom, early referral, and adherence to evidence-based management are critical to reducing snakebite-related mortality in Sudan. Author SummarySnakebite envenoming is a neglected tropical disease that disproportionately affects rural and agricultural communities in low-resource settings. In Sudan, snakebite remains a major but underreported cause of illness and death. One of its most serious complications is venom-induced consumption coagulopathy (VICC), a disturbance of blood clotting that can lead to severe bleeding and organ failure. We studied all patients admitted with snakebite envenoming to a teaching hospital in southeastern Sudan over six months. More than 80% of patients developed VICC, most often following bites attributed to Echis species, which are common in this region. Many patients experienced spontaneous bleeding, and nearly one-third developed life-threatening hemorrhage, most frequently bleeding in the brain. Acute kidney injury was common. Despite supportive treatment, almost one-third of patients with VICC died, and all children in the study died. Our findings highlight the severe and largely preventable burden of snakebite envenoming in this setting. Delayed presentation to hospital, reliance on traditional healers, and the lack of effective antivenom against locally prevalent snake species contributed to poor outcomes. This study highlights the urgent need to improve access to appropriate antivenom, strengthen health-care systems, and implement evidence-based management of snakebite envenoming to reduce avoidable deaths and disability in Sudan.

Background and AimsAcetaminophen (APAP) overdose is the leading individual cause of acute liver failure (ALF) in the United States, with many patients rapidly progressing to hyperacute liver failure. While hepatocytes are the main target of APAP toxicity, endothelial cells (ECs) are also affected. However, the efficacy of an endothelial-specific biomarker to predict patient outcomes remains unknown. This study aimed to evaluate angiopoietin-2 (ANGPT2) as a prognostic biomarker for poor outcomes in APAP-induced ALF. Approach and ResultsUsing human and mouse single-cell RNA sequencing (scRNAseq) data, we found that ANGPT2 expression was significantly elevated in ECs following APAP exposure. We measured circulating ANGPT2 levels from two independent APAP-ALF cohorts: a Phoenix cohort (n=43) and a cohort from the ALF Study Group (n=80). In the Phoenix cohort, ANGPT2 levels were significantly higher in non-survivors with an AUROC of 0.938. In the ALFSG cohort, we stratified patients based on time of symptom onset finding that ANGPT2 had improved prognostic value in early-presenting patients, with day 1 and day 3 AUC values of 0.825 and 0.918, respectively. Lastly, we combined the patient cohorts (n=110) finding that ANGPT2 alone or in combination with MELD outperformed MELD alone based on AUC (ANGPT2: 0.87, MELD 0.83, ANGPT2+MELD 0.90). ConclusionsANGPT2 is a promising prognostic biomarker for APAP-induced ALF, reflecting endothelial stress and offering superior predictive value compared to MELD alone, especially in early-presenting patients. Its capacity for predicting poor outcomes underscores its value in improving patient prognosis and therapeutic intervention strategies in APAP overdose cases. Lay SummaryAccidental or intentional overdosing on acetaminophen can cause liver injury and in severe cases acute liver failure. Under these circumstances, receiving a liver transplant may be the only remaining therapeutic option. However, a liver transplant is a major surgery and commits the patient to a lifetime of anti-rejection medication. Because there is only a limited time window to decide who will recover and who needs a transplant to survive, prognostic biomarkers are essential to identify transplant candidates as early as possible after the overdose. In this study we discovered that plasma levels of the endothelial growth factor angiopoietin-2 can accurately predict at the peak of injury who will need a liver transplant to survive. In addition, this biomarker can be rapidly measured, which allows the data to be available for clinical decision making. HighlightsO_LIAcetaminophen-induced liver injury can cause hyper-acute liver failure within 3 to 7 days with a high probability of negative outcome. C_LIO_LIUnder these conditions, a liver transplant may be the only therapeutic option. C_LIO_LIIn two independent cohorts, angiopoietin 2 was identified as an early prognostic biomarker for poor outcome. C_LIO_LIAngiopoietin can more accurately inform clinical management during the initial stages of hospital presentation than the MELD score. C_LI

BackgroundDespite a fingerstick hemoglobin requirement and 56-day minimum donation interval, repeat blood donation continues to cause and exacerbate iron deficiency. Study design and methodsUsing data from the REDS-II Donor Iron Status Evaluation study, we developed multiclass prediction models to estimate the competing risk of hemoglobin deferral and collecting blood from a donor with sufficient hemoglobin but low or absent underlying iron stores. We compared models developed with and without two biomarkers not routinely measured in most blood centers: ferritin and soluble transferrin receptor. We generated and analyzed individual risk trajectories: estimates of how each donors risk developed as a function of the time interval until their next donation attempt. ResultsWith standard biomarkers, the top model had a multiclass area under the receiver operator characteristic curve (AUC) of 77.6% (95% CI 77.3% - 77.8%). With extra biomarkers, multiclass AUC increased to 82.8% (95% CI 82.5% - 83.1%). In the extra biomarkers model, ferritin was the single most important variable, followed by the donation interval. We identified three risk archetypes: fast recoverers (<10% risk of any adverse outcome on post-donation day 56), slow recoverers (>60% adverse outcome risk on day 56 that declines to <35% by day 250), and chronic high-risk (>85% risk of adverse outcome on day 250). DiscussionA longer donation interval reduced estimated risk of iron-related adverse events for most donors, but risk remained high for some. Tailoring safeguards to individual risk estimates could reduce blood collections from donors with low or absent iron stores.

BackgroundMajor blood centers perform serologic testing on potential COVID-19 convalescent plasma donors retrospectively after blood donation. A hospital-based recruitment program for COVID-19 convalescent plasma (CCP) donors may be an efficient way to prospectively identify potential donors. Study Design and MethodsPatients who recovered from known or suspected COVID-19 were identified and recruited through medical record searches and public appeals. Participants were screened with a modified donor history questionnaire (DHQ), and if eligible, were consented and tested for SARS-CoV-2 antibodies (IgG and IgM). Participants who were positive for SARS-CoV-2 IgG were referred to a local blood center for convalescent plasma collection. ResultsOf 179 individuals screened, 128 completed serologic testing and 89 were referred for convalescent plasma donation to a local blood center (49.7% of those screened). IgG antibodies to SARS-CoV-2 were detected in 23/51 (45.1%) of participants with suspected COVID-19 and in 66/77 (85.7%) of participants with self-reported PCR-confirmed COVID-19. Testing was performed at a median of 38 days since last symptoms. Participant age positively correlated with anti-SARS-CoV-2 IgG and IgM levels. Time since last symptoms did not correlate with IgG or IgM levels. A wide range of SARS-CoV-2 IgG levels were observed. ConclusionA hospital based CCP donor recruitment program can prospectively identify potential CCP donors. Variability in SARS-CoV-2 IgG levels has implications for selection of CCP units for transfusion.

BackgroundRibavirin (RBV) is been used for SARS-CoV-2 infection. This drug is associated with a wide range of side effects, mainly anemia, so its use in patients with potential respiratory affectation could not be appropriate. The evidences of adverse events associated with RBV-use has mainly been derived in the context of hepatitis C (HCV) treatment, however the possible use of RBV in CoVID-19 patients could be limited to 14 days. MethodsLongitudinal study including HIV/HCV coinfected patients. We evaluate the hemoglobin dynamics and reductions as well as evaluate the development rate of anemia during the first 2 weeks of therapy in HCV infected patients. Results189 patients were included in the study. The median hemoglobin levels were 14.6 g/dL (IQR: 13.2-15.6 g/dL) and 13.5 g/dL (IQR: 12.3-14.5 g/dL) at weeks 1 and 2 of therapy, respectively. A cumulative number of 27 (14.2%) patients developed anemia (23 grade 1 [12.1%] and 4 grade 2 [2.1%]). We identify a baseline hemoglobin levels of 14 g/dL as the better cut-off to identify those patients with a high chance to develop anemia. Of the 132 patients with baseline hemoglobin level >14 g/dL, 8 developed anemia (6.1%) compared with 19 of 57 (33.3%) with hemoglobin levels lower than 14 g/dL (p < 0.001). ConclusionsOur study shows valuable information about the early hemoglobin kinetic timing in patients on RBV-therapy, that could be useful to tailor CoVID-19 treatment if RBV use is considered.

BackgroundThe novel coronavirus, SARS-CoV2 that causes COVID-19 has resulted in the death of more than 2.31 million people within the last year and yet no cure exists. Whereas passive immunization with COVID-19 convalescent plasma (CCP) provides a safe and viable option, selection of optimal units for therapy and lack of clear therapeutic benefit from transfusion remain as barriers to the use of CCP. Study design and methodsTo identify plasma that is expected to benefit recipients, we measured anti-SARS-CoV2 antibody levels using clinically available serological assays and correlated with the neutralizing activity of CCP from donors. Neutralizing titer of plasma samples was measured by assaying infectivity of SARS-CoV-2 spike protein pseudotyped retrovirus particles in the presence of dilutions of plasma samples. We also used this assay to identify evidence of passive transfusion of neutralizing activity in CCP recipients. ResultsViral neutralization and anti-spike protein antibodies in 109 samples from 87 plasma donors were highly varied but modestly correlated with each other. Recipients who died of COVID-19 were found to have been transfused with units with lower anti-spike antibody levels and neutralizing activity. Passive transfer of neutralization activity was documented in 62% of antibody naive plasma recipients. ConclusionsSince viral neutralization is the goal of CCP transfusion, our observations not only support the use of anti-spike SARS-CoV2 serology tests to identify beneficial CCP units, but also support the therapeutic value of convalescent plasma with high titers of anti-spike antibodies.

BackgroundTo identify blood donors eligible to donate Coronavirus Disease-2019 (COVID-19) Convalescent Plasma (CCP), a large blood center began testing for antibodies to SARS-CoV-2, the etiologic agent of COVID-19. We report the seroprevalence of total immunoglobulin directed against the S1 spike protein of SARS-CoV-2 in US blood donors. MethodsUnique non-CCP donor sera from June 1-July 31, 2020 were tested with the Ortho VITROS Anti-SARS-CoV-2 total immunoglobulin assay (positive: signal-to-cutoff (S/C) [&ge;]1). Donor age, sex, race/ethnicity, ABO/RhD, education, and experience were compared to June and July 2019. Multivariate regressions were conducted to identify demographics associated with the presence of antibodies and with S/C values. ResultsUnique donors (n=252,882) showed an overall seroprevalence of 1.83% in June (1.37%) and July (2.26%), with the highest prevalence in northern New Jersey (7.3%). In a subset of donors with demographic information (n=189,565), higher odds of antibody reactivity were associated with non-Hispanic Native American/Alaskan (NH-NAA/A) and Black (NH-B), and Hispanic (H) race/ethnicity, age 18-64, middle school or lesser education, blood Group A, and never or non-recent donor status. In positive donors (n=2,831), antibody signal was associated with male sex, race/ethnicity (NH-NAA/A, NH-B and H) and geographic location. ConclusionsSeroprevalence remains low in US blood donors but varies significantly by region. Temporal trends in reactivity may be used to gauge the effectiveness of public health measures. Before generalizing these data from healthy donors to the general population however, rates must be corrected for false positive test results among low prevalence test subjects and adjusted to match the wider demography.

BackgroundDaboia palaestinae is a leading cause of snakebite envenomation in the eastern Mediterranean, with substantial mortality in absence of antivenin. Current recommended antivenin dose is 50 ml; however, antivenin is costly, may be difficult to obtain and is associated with substantial morbidity. Thus, this study was designed to define the minimal effective antivenin dose and identify patients who can be safely treated without antivenin. MethodsThis retrospective single-center study was conducted in adults with suspected or confirmed D. palaestinae envenomation. Patients were treated via our previously developed envenomation protocol: no antivenin use for local symptoms and dose scaling for mild or severe systemic symptoms - initially 10 ml antivenin, with repeat dosing for ongoing systemic symptoms. Main outcomes measured were morbidity and mortality associated with this protocol. Secondary outcomes included assessing the demographics and clinical effects of snake envenomation and comparing between those who received antivenin and those who did not. Results101 patients were included. 45 minutes [median; interquartile range: 30-61 minutes] elapsed between envenomation and hospital admission, with no differences between groups. Among 52 patients receiving antivenin, 119 [60-237] minutes elapsed between envenomation and initial antivenin administration, with a maximum of 1073 minutes to initial anvenin administration. Maximum until last antivenin was 3860 minutes. Median antivenin dose was 15 [10-22.5] ml, with 26/52 (50.0%) requiring only 10 ml. 2 patients developed an early antivenin immune reaction, with 1 developing anaphylaxis requiring invasive ventilation. No patients died during hospitalization. ConclusionsThis cohort demonstrates that a dose-scaling antivenin protocol can be safely employed, reducing morbidity and costs. This suggests a randomized control trial comparing fixed dose regimen to an escalation protocol and development of similar protocols for envenomations due to other snake species.

BackgroundCharacterizing the kinetics of the antibody response to SARS{square}CoV{square}2 is of critical importance to developing strategies that may mitigate the public health burden of COVID-19. We sought to determine how circulating antibody levels change over time following natural infection. Methods/MaterialsWe conducted a prospective, longitudinal analysis of COVID-19 convalescent plasma (CCP) donors at multiple time points over a 9-month period. At each study visit, subjects either donated plasma or only had study samples drawn. In all cases, anti-SARS-CoV-2 donor testing was performed using semi-quantitative chemiluminescent immunoassays (ChLIA) targeting subunit 1 (S1) of the SARS-CoV-2 spike (S) protein, and an in-house fluorescence reduction neutralization assay (FRNA). ResultsFrom April to November 2020 we enrolled 202 donors, mean age 47.3 {+/-}14.7 years, 55% female, 75% Caucasian. Most donors reported a mild clinical course (91%, n=171) without hospitalization. One hundred and five (105) (52%) donors presented for repeat visits with a median 42 (12-163) days between visits. The final visit occurred at a median 160 (53-273) days post-symptom resolution. Total anti-SARS-CoV-2 antibodies (Ab), SARS-CoV-2 specific IgG and neutralizing antibodies were detected in 97.5%, 91.1%, and 74% of donors respectively at initial presentation. Neutralizing Ab titers based on FRNA50 were positively associated with mean IgG levels (p = <0.0001). Mean IgG levels and neutralizing titers were positively associated with COVID-19 severity, increased donor age and BMI (p=0.0006 and p=0.0028, p=0.0083 and p=0.0363, (p=0.0008 and p=0.0018, respectively). Over the course of repeat visits, IgG decreased in 74.1% of donors; FRNA50 decreased in 44.4% and remained unchanged in 33.3% of repeat donors. A weak negative correlation was observed between total Ab levels and number of days post-symptom recovery (r = 0.09). ConclusionAnti-SARS-CoV-2 antibodies were identified in 97% of convalescent donors at initial presentation. In a cohort that largely did not require hospitalization. IgG and neutralizing antibodies were positively correlated with age, BMI and clinical severity, and persisted for up to 9 months post-recovery from natural infection. On repeat presentation, IgG anti-SARS-CoV-2 levels decreased in 56% of repeat donors. Overall, these data suggest that CP donors possess a wide range of IgG and neutralizing antibody levels that are proportionally distributed across demographics, with the exception of age, BMI and clinical severity.

In March 2020, the FDA approved the use of COVID-19 convalescent plasma (CCP) as an investigational new drug for treatment of COVID-19. Since then, collection of CCP from COVID-19 recovered patients has been implemented in several donor centers across the country. Childrens Hospital Colorado rapidly put into practice a CCP collection protocol, necessitating the development and implementation of assays to evaluate SARS-CoV-2 antibodies in CCP units. We evaluated 87 separate units of CCP collected from 36 donors over two to four sequential donations using both antigen- binding assays for SARS-CoV-2 nucleoprotein and spike antigens, and a live virus focus reduction neutralization test (FRNT50). Our data shows that the majority of donors (83%) had a FRNT50 titer of 1:80 or greater, and 61% had a titer [&ge;] 1:160, which meet the FDAs criteria for acceptable CCP units. Additionally, our data indicates that analysis of antibodies to a single SARS-CoV-2 antigen is likely to miss a percentage of seroconverters; however, these individuals tend to have neutralizing antibody titers of <1:80. Of note, there was considerable variability in the short term, sustained antibody response, measured by neutralizing antibody titers, among our donor population.

Amatoxin-induced acute liver failure complicates misidentified foraged mushroom ingestion worldwide; abrupt multisystem collapse punctuates apparent improvement. Our prospective single-arm clinical trial investigated proactive toxicokinetic-based management to preserve elimination capacity: sustained enhanced hydration to maintain renal clearance; fasting plus octreotide to suppress meal-driven enterohepatic circulation; and intravenous silibinin to inhibit OATP1B3-mediated hepatic uptake, enabling safe passage and elimination of gallbladder-confined amatoxin-laden bile. Safety population (N=99) transplant-free recovery (TFR): 88.0% (87 recoveries, 6 transplants, 6 deaths). Protocol-adherent Efficacy population (n=86) TFR: 98.8% (85 recoveries, 1 transplant, 0 deaths). Multivariable analysis identified uninterrupted hydration as strongest TFR predictor (P<0.001), followed by earlier silibinin initiation (P=0.003); octreotide shortened INR recovery by 11 hours (P=0.033). These findings support a toxin elimination model in which preserved renal clearance and biliary sequestration are central recovery determinants. The kinetic balance between renal clearance and hepatic uptake governs both recovery and collapse.

ObjectiveThis study aimed to evaluate the impact of combined use of chemiluminescent immunoassay (CLIA) and nucleic acid amplification testing (NAAT) to improve transfusion transmitted Hepatitis B Virus (HBV), Hepatitis C virus (HCV) and Human Immunodeficiency Virus-1 (HIV-1) among blood donors in Pakistan. DesignRetrospective, single center observational. SettingRegional blood center at tertiary care hospital in urban Pakistan. ParticipantsAll adults of 18 years or above who were eligible to donate blood after meeting the pre-donation screening criteria during the study period (n = 26,778). Outcome MeasuresPrimary outcome measure was to estimate the incremental yield of HBV, HCV, and HIV-1 infections using combined CLIA+NAAT compared to CLIA-alone per 100,000 donations. Secondary outcome was to calculate inter-test agreement and discordance between CLIA and NAAT methods. ResultsAmong 26,778 donors, the combined CLIA+NAAT testing detected a total of 2,423.6 viral infections per 100,000 donations, NAAT alone contributed 739.7/100,000 of these. For HBV, NAAT uniquely detected 489/100,000 additional cases missed by CLIA; the combined detection rate was 1,561/100,000. For HCV, NAAT-only yield was lower (247/100,000), with total detection of 825.3/100,000. HIV-1 was rare in the donor pool; incremental NAAT yield was 3.7/100,000, with a combined detection rate of 37.3/100,000. Agreement between tests was substantial for HBV ({kappa} = 0.63) and moderate to fair for HCV ({kappa} = 0.47) and HIV-1 ({kappa} = 0.40). The discordant cases detected by NAAT alone for HBV, HCV and HIV-1 were 183, 431 and 37 respectively. McNemars test showed statistically significant differences (p < 0.001) across all markers, with large effect sizes for HIV-1 (0.92, 95% CI: 0.80-1.00) and HCV (0.69, 95% CI: 0.65-0.73). ConclusionIntegrating CLIA with NAAT enhanced the detection of HBV, including occult and window period infections, and refined estimates of active HCV and HIV-1 infections which significantly improved blood transfusion safety. STRENGTHS AND LIMITATIONS OF THIS STUDYO_LIThe selection bias was reduced by including all consecutive eligible blood donors during study period. C_LIO_LIThe information bias was minimized through uniform, fully automated, and validated protocols for combined CLIA and NAAT testing of blood donors. C_LIO_LIThe single center retrospective study design restricts generalizability and causal inference. C_LIO_LIThe false positives/negatives and genetic variability were not confirmed. C_LI

Structured AbstractO_ST_ABSBackgroundC_ST_ABSCivilian walking blood banks (WBBs) transfuse fresh whole blood from mobilized donors, screened using rapid diagnostic testing (RDT) for transfusion transmissible infections (TTIs), to preserve life when banked blood is unavailable. However, concerns regarding TTI risk using a RDT process instead of a more traditional, laboratory-based test persist. We aimed to understand the marginal risk of TTI using an RDT-based strategy compared to a laboratory-based test through development of a simulation model and accompanying online tool. Study Design and MethodsWe modeled expected TTIs per 100,000 donations from initial collection to transfusion and seroconversion. Parameters included TTI prevalence, donor risk-stratification, efficacy of stratification tools, TTI testing rates, platform test performance, and probability of seroconversion. ResultsA baseline TTI prevalence of 1% (95% CI: 0.25%, 1.75%) resulted in 56 TTIs (95% CI: 23, 91) when the RDT sensitivity was 90% (95% CI: 88%, 92%), 30 TTIs (95% CI: 12, 52) when the RDT sensitivity was 95% (95% CI: 93%, 97%), and 12 TTIs (95% CI: 4, 23) when the RDT sensitivity was 99% (95% CI: 97, 100%) per 100,000 donations. Compared to lab-based testing, 15,351 donations would need to be made under a high-sensitivity RDT testing strategy in order to incur one additional TTI. DiscussionIn a simulated WBB model, modern RDT platforms demonstrated favorable test characteristics, with low absolute rates of TTI, particularly when low-risk donors are selected. These findings support WBB implementation as an emergency transfusion strategy in settings lacking banked blood.

BackgroundConvalescent plasma therapy for COVID-19 relies on the transfer of anti-viral antibody from donors to recipients via plasma transfusion. The relationship between clinical characteristics and antibody response to COVID-19 is not well defined. We investigated predictors of convalescent antibody production and quantified recipient antibody response in a convalescent plasma therapy clinical trial. MethodsMultivariable analysis of clinical and serological parameters in 103 confirmed COVID-19 convalescent plasma donors 28 days or more following symptom resolution was performed. Mixed effects regression models with piecewise linear trends were used to characterize serial antibody responses in 10 convalescent plasma recipients with severe COVID-19. FindingsMean symptom duration of plasma donors was 11.9{+/-}5.9 days and 7.8% (8/103) had been hospitalized. Antibody titers ranged from 0 to 1:3,892 (anti-receptor binding domain (RBD)) and 0 to 1:3,289 (anti-spike). Multivariable analysis demonstrated that higher anti-RBD and anti-spike titer were associated with increased age, hospitalization for COVID-19, fever, and absence of myalgia (all p<0.05). Fatigue was significantly associated with anti-RBD (p=0.03) but not anti-spike antibody titer (p=0.11). In pairwise comparison among ABO blood types, AB donors had higher anti-RBD titer than O negative donors (p=0.048) and higher anti-spike titer than O negative (p=0.015) or O positive (p=0.037) donors. Eight of the ten recipients were discharged, one remains on ECMO and one died on ECMO. No toxicity was associated with plasma transfusion. After excluding two ECMO patients and adjusting for donor antibody titer, recipient anti-RBD antibody titer increased on average 31% per day during the first three days post-transfusion (p=0.01) and anti-spike antibody titer by 40.3% (p=0.02). InterpretationAdvanced age, fever, absence of myalgia, fatigue, blood type and hospitalization were associated with higher convalescent antibody titer to COVID-19. Despite variability in donor titer, 80% of convalescent plasma recipients showed significant increase in antibody levels post-transfusion. A more complete understanding of the dose-response effect of plasma transfusion among COVID-19 patients is needed to determine the clinical efficacy of this therapy. Trial RegistrationNCT04340050 FundingDepartment of Surgery University of Chicago, National Institute of Allergy and Infectious Diseases (NIAID) Collaborative Influenza Vaccine Innovation Centers (CIVIC) contract 75N93019C00051

IntroductionThe efficacy of SARS-CoV2 standard single donor convalescent plasma varied according to the application time and most importantly the amount of antibody that is administered. Single donor plasma has some drawbacks; such as the insufficient levels of neutralizing antibody activities, the requirements of blood group compatibility, and the risk of infection transmission. In this study, the efficacy and safety of pathogen inactivated, isohemagglutinin-depleted (concentrated) and pooled convalescent plasma was investigated. MethodsIn this study, ACB-IP 1.0 convalescent plasma product was prepared as follows; first, convalescent plasma was collected from different donors, then pathogen-inactivation was carried-out, and isohemagglutinins were cryodepleted, respectively. Finally, concentrated convalescent plasma product was pooled and stored until use. A total of sixteen patients were treated with two different convalescent plasma products. Nine patients were treated with standard single donor convalescent plasma and seven were treated with pathogen-free, concentrated, pooled convalescent plasma (ACB-IP 1.0) between 01 March 2020 and 31 December 2020. The outcomes of these two plasma products were compared regarding SARS-CoV2 antibody titers, neutralizing antibody activities, length of hospitalization and mortality rates. ResultsFive out of six single donor plasma SARS-CoV2 antibody titers remained below 12 s/co, but the antibody titers of all ACB-IP 1.0 plasma were above 12 s/co. SARS-CoV2 total antibody titers of ACB-IP 1.0 plasma were statistically higher than the antibody titers of single donor plasma. Mean total plasma neutralizing antibody activity of ACB-IP 1.0 plasma (1.5421) was found statistically higher than single donor plasma (0.9642) in 1:256 dilution ({rho}=0.0087) The mortality rate of the patients treated with ACB-IP 1.0 plasma showed statistically lower (p: 0,033) than the patients treated with single donor plasma. The administration of either single donor plasma or ACB-IP 1.0 plasma to the patients within eight days significantly shortened the length of hospitalization compared to administration of either plasma to the patients later than eight days ({rho}= 0,0021) DiscussionPathogen-free, concentrated, pooled convalescent plasma may resolve the bias in SARS-CoV2 antibody titers and neutralizing antibody activities, without requiring blood group compatibility that allows patient accessibility in a shorter time and has safe plasma characteristic. This study indicates that ACB-IP 1.0 may be a superior product compared to standard single donor plasma.

BACKGROUNDEfficacy of COVID-19 convalescent plasma (CCP) to treat COVID-19 is hypothesized to be associated with the concentration of neutralizing antibodies (nAb) to SARS-CoV-2. High capacity serologic assays detecting binding antibodies (bAb) have been developed, nAb assays are not adaptable to high-throughput testing. We sought to determine the effectiveness of using surrogate bAb signal-to-cutoff ratios (S/CO) in predicting nAb titers using a pseudovirus reporter viral particle neutralization (RVPN) assay. METHODSCCP donor serum collected by 3 US blood collectors was tested with a bAb assay (Ortho Clinical Diagnostics VITROS Anti-SARS-CoV-2 Total, CoV2T) and a nAb RVPN assay. CoV2T prediction effectiveness at S/CO thresholds was evaluated for RVPN nAb NT50 titers using receiver operating characteristic analysis. RESULTS753 CCPs were tested with median CoV2T S/CO of 71.2 and median NT50 of 527.5. Proportions of CCP donors with NT50 over various target nAb titers were 86% [&ge;]1:80, 76% [&ge;]1:160, and 62%[&ge;]1:320. Increasing CoV2Ts reduced the sensitivity to predict NT50 titers, while specificity to identify those below thresholds increased. As the targeted NT50 increased, the positive predictive value fell with reciprocal increase in negative predictive value. S/CO thresholds were thus less able to predict target NT50 titers. CONCLUSIONSelection of a clinically effective nAb titer will impact availability of CCP. Product release with CoV2T assay S/CO thresholds must balance the risk of releasing products below target nAb titers with the cost of false negatives. A two-step testing scheme may be optimal, with nAb testing on CoV2T samples with S/COs below thresholds.

The hypothesis for this study was that RBC mechanical fragility (MF) could be an aggregate in vitro property predictive of transfused RBC performance in vivo. Various MF values were obtained via MF profiling, based on several variations of testing parameters, using both a "legacy" approach (with a commercial, cam-based vertical bead mill and a spectrophotometer) and a more proprietary approach (with a custom-developed, electromagnetic horizontal bead mill combined with proprietary optics and analysis). A total of 52 transfusion events in 32 different patients recruited from the University of Michigan were included in this study. Results were assessed using mixed effects and linear regression models. RBC MF was shown to predict about 15% of transfusion-associated changes in patient hemoglobin concentration, but not of secondary hemolysis-associated metrics (serum hemoglobin, HAP, and LDH). This result was affected by several factors that were not fully accounted for, including variability in post-transfusion blood collection time and variability in each blood unit volumes. Inclusion of the number of units transfused showed the potential to improve predictive capability, thus highlighting the potential importance of underlying patient condition necessitating the second unit transfusion. Certain ways of applying the bead-induced mechanical stress showed MF results more suitable for predicting transfusion outcomes than others indicating potential significance of flow stress type for assessing storage-induced RBC membrane damage. That highlights an opportunity for improvement of the potential for use of MF metrics, through identification of optimal stress application parameters (possibly by further varying parameters used here, as well as others) for assessing contribution of storage-lesion-associated RBC damage on transfused RBC performance.

BackgroundThere is a large inter-individual variation in CD34+ cell yield after G-CSF mobilisation and collection from peripheral blood in healthy allogenic haematopoietic stem cell donors. Donor characteristics including gender and age, baseline and pre-collection blood results, mobilisation factors and collection factors have been associated with CD34+ cell concentration in the blood after G-CSF mobilisation and/or CD34+ cell yield after collection. Since the literature reporting these associations is heterogeneous, we here clarify the determinants of CD34+ cell concentration and yield through a scoping literature review. Materials and MethodsMEDLINE, Embase, PubMed and Stem Cell Evidence were searched for studies published between 2000 and 2023. The inclusion criteria were studies of allogeneic donors undergoing G-CSF mobilisation and peripheral blood stem cell collection (PBSC). Eligible studies assessed an outcome of mobilisation or collection efficacy, indicated by the blood CD34+ cell concentration after 4 or 5 days of G-CSF treatment and/or CD34+ cell yield in the first PBSC collection after mobilisation. Included studies assessed associations between these outcomes and donor factors (such as age, gender, weight, ethnicity), mobilisation factors (G-CSF scheduling or dose), collection factors (venous access, processed blood volume) and laboratory factors (such as blood cell counts at baseline and after mobilisation). ResultsThe 51 eligible studies evaluated between 23 and 20,884 donors. 43 studies were retrospective, 32 assessed blood CD34+ cell concentration after mobilisation and 37 assessed CD34+ cell yield. In studies that recorded both outcomes, blood CD34+ cell concentration always predicted CD34+ cell yield. The most frequently assessed factor was donor age for which most studies reported that younger donors had a higher blood CD34+ cell concentration and CD34+ cell yield. Non-European ancestry was associated with both higher blood CD34+ cell concentration and yield although this finding was inconsistent. ConclusionsThere remains poor consensus about the best predictors of blood CD34+ cell concentration and yield that requires further prospective study, particularly of the role of donor ancestry. The current focus on donor gender as a major predictor may require re-evaluation.