Jacquot, Cyril

Importance Recent case reports suggest that B antigen–containing blood products may be associated with anaphylactic transfusion reactions in recipients with preformed immunoglobulin E to galactose- α -1,3-galactose (alpha-gal). Objective To test the association of local alpha-gal syndrome (AGS) prevalence and allergic transfusion reaction (ATR) in patients with blood type O. Design, Setting, and Participants In this international, multicenter, retrospective cohort study at academic medical centers, sites were assigned to AGS high- or low-prevalence clusters based on the known geographic distribution of AGS. Data were collected on platelet or plasma transfusions and ATRs during 2020 to 2024. Consecutive patients receiving platelet or plasma transfusions were included. Exposures Patients with blood type O who received B or AB units and patients with blood type O who received O units (reference group) in AGS high- and low-prevalence clusters were compared. Main Outcomes and Measures Before data collection, the hypothesis was that if transfusion-related alpha-gal syndrome (TRAGS) is a true clinical entity, excess ATRs to group B or AB units would be detected in AGS high-prevalence regions exclusively. The main measure was the overall risk ratio (RR) for ATRs to B or AB plasma or platelets in AGS high- vs low-prevalence clusters. Results In total, 558 823 platelet and plasma transfusions at 40 sites in 5 countries were analyzed, of which ATRs occurred in 1744 transfusions (0.3%). In the US AGS high-prevalence cluster (9 sites), significantly more ATRs of any severity occurred among patients with blood type O who received B or AB units vs patients with blood type O who received O units (overall RR, 3.93; 95% CI, 2.96-5.21; P < .001). In contrast, in the primary analysis of the AGS low-prevalence cluster (15 sites), excess ATRs to B or AB units were not detected. In subgroup analyses among patients with blood type O receiving B units, the RR for moderate to severe ATRs was 9.14 (95% CI, 5.39-15.52; P < .001) in the AGS high-prevalence cluster vs 2.15 (95% CI, 1.34-3.47; P = .002) in the AGS low-prevalence cluster. Outside the US, a signal consistent with TRAGS was not detected. Conclusions and Relevance This cohort study provides provocative epidemiologic evidence that TRAGS may be a unique manifestation of AGS and a previously unrecognized risk associated with transfusion. In AGS high-prevalence regions, blood collectors and hospital transfusion services should consider approaches to preventing severe ATRs from B or AB plasma or platelet units.

Abstract Introduction: The Duffy null variant (genotype or phenotype) is associated with lower circulating absolute neutrophil counts (ANC) without increased risk for infection. It is found in ~66% of people identifying as Black or African American vs <1% of people of Asian or European ancestry. Many ANC reference intervals (RI) are not representative of the Duffy null population. There are no adult Duffy null WBC RI and no pediatric Duffy null ANC or WBC RI. Thus, we aimed to assess Duffy null ANC and WBC distributions as well as develop WBC and ANC RI for adults and pediatrics. Methods: Twenty-three sites across the United States collected samples with all sites excluding participants with conditions or medications that could impact ANC or WBC. Only Duffy null participants were included. Sex, race, ethnicity, age, sample collection type, practice setting, Duffy testing method, ANC, and WBC were recorded. The non-parametric method for determining lower limit of normal (LLN), upper limit of normal (ULN), and 90% confidence intervals (CI) around the limits was performed according to the Clinical and Laboratory Standards Institute guidelines. Specific ULN and LLN are not reported as these are preliminary data. The Mann-Whitney U test was used to compare sex and prior data; differences by age groups were assessed with Kruskal-Wallis test. Results: 316 participants 18+ years-old (y/o) were assessed of whom 62.3% (n=197) are female, 97.5% (n=308) identified as Black or African American, and 94.9% (n=300) identified as non-Hispanic. Median age was 47 y/o (IQR: 32-60.5). Median ANC was 2600/uL (IQR: 1860-3530; range: 400-7400); 28.6% (n=90) of participants had ANC <2000/uL, 13.6% (n=43) had ANC <1500/uL, and 2.5% (n=8) had <1000/uL. The 90% CI around the LLN was 810-1070/uL and 5570-7130/uL around the ULN. Consistent with prior data, there was a difference in median ANC by sex (male: 2400/uL; female: 2710/uL; p=0.02). There was no significant difference between this ANC data and previously published Duffy null ANC data (p=0.28). Median WBC was 5.4x109/L (IQR: 4.4-6.5; range: 2.10-11.64) with 4.1% (n=13) of participants with WBC <3.0x109/L. The 90% CI around the LLN is 3.68-4.30x109/L and 11.02-12.97x109/L around the ULN. 515 participants between 0-17 y/o were assessed with 51.8% (n=267) females, 94.8% (n=488) identified as Black or African American, and 94.0% (n=484) identified as non-Hispanic. Among pediatric participants, 56.8% (n=291) had ANC <2000/uL, 38.7% (n=198) had ANC <1500/uL, and 14.4% (n=74) had ANC <1000/uL. For those <1 y/o (n=29), median ANC was 950/uL (IQR: 840-1360; range: 111-3910). There are currently too few samples to predict ULN and LLN. Median WBC was 8.85x109/L (IQR: 7.03-10.16; range: 4.17-13.53). For those 1-5 y/o (n=143), median ANC was 1735/uL (IQR: 1100-2550; range: 207-5810) with a 90% CI around the LLN of 207-820/uL and 4020-5810/uL around the ULN. Median WBC was 6.72x109/L (IQR: 5.64-8.25; range: 3.68-12.97). For those 6-11 y/o (n=128), median ANC was 1590/uL (IQR: 1090-2470; range: 420-5490) with a 90% CI around the LLN of 420-910/uL and 4340-5490/uL around the ULN. Median WBC was 5.42x109/L (IQR: 4.45-6.70; range: 2.80-10.50). For those 12-17 y/o (n=215), median ANC was 2190/uL (IQR: 1460-2930; range: 204-5850) with a 90% CI around the LLN of 540-930/uL and 4350-5510/uL around the ULN. Median WBC was 5.06x109/L (IQR: 4.26-6.20; range of 2.04-9.91). There is a significant difference in ANC by age category (p<0.0001). Conclusion: This is the first report of healthy pediatric Duffy null ANC and WBC data and the first large-scale verification of adult Duffy null ANC and WBC data. Final RI are expected in September 2025. Among adults with the Duffy null phenotype, ANC LLN are likely between 810-1070/uL. Pediatric ANC LLN are likely as low as 207-820/uL (1-5 y/o), 420-910/uL (6-11 y/o), and 540-930/uL (12-17 y/o). These findings redefine “normal” as a significant proportion of healthy participants have ANC or WBC below current RI or below thresholds typically defined as disease. Limitations include heterogeneous sample populations and collection methods. Future analyses will assess differences between collection sites or methods. Ultimately, this work lays the foundation for a more scientifically sound and equitable approach to medical care by ensuring that RI accurately reflects health for the entire community. Healthcare systems are strongly encouraged to adopt Duffy null-specific ANC and WBC RI.

Abstract Background Cryoprecipitated antihemophiliac factor (cryo) is primarily used to replenish fibrinogen in acquired coagulopathy. Little has been reported about its usage patterns within hospitals with respect to patient population, frequency of use, and dosing. Study design and methods Cryo production and usage data were collected over 5 years from July 1, 2016, to June 30, 2021, from nationally based blood collection centers in the United States (U.S. n = 2) and Canada ( n = 2) and from eight large academic hospitals, respectively. Usage data for a similar product, purified fibrinogen concentrate were also collected from four hospitals. Results Two U.S. blood collectors reported increases in cryo production normalized to total whole blood collections from 17.4% in 2016 to 22.3% in 2021 and from 16.4% in 2016 to 20.2% in 2021. In contrast, in Canada cryo manufacturing increased slightly in one region (11.3%–12.9%) and decreased (8.0%–2.0%) in the other. Cryo utilization, defined as numbers of patients treated normalized to the inpatient census, and dose administered per patient did not consistently increase and differed significantly between hospitals participating in the study ( p < .0001). Likewise, the departments that most frequently transfused cryo varied between hospitals. Similarly, variations in practice were observed for fibrinogen concentrate usage. Conclusion While much of Canada and Europe have moved towards using fibrinogen concentrate, two large U.S. collectors have increased cryo distribution. The lack of standardization and variability in the clinical practice regarding the use of cryo and fibrinogen concentrate reported by study sites may be attributable to practitioner preference, availability, and/or cost rather than adherence to published evidence or guidelines.

Abstract Background Rho(D) immune globulin (RhIg) is used to reduce RhD alloimmunization in pregnancy. This study describes potential causes for RhD alloimmunization after the development and implementation of RhIg. Study Design and Methods This retrospective descriptive study investigated RhD‐negative patients born in 1965–2005 with anti‐D newly identified during 2018–2022. Transfusion, pregnancy, intravenous drug abuse, and transplantation were considered potential alloimmunization sources. Results There were 1200 study patients (852 females; 348 males) at 30 institutions in 5 countries (USA, Canada, UK, New Zealand, Brazil). Most patients had a single potential source of alloimmunization identified (857/1200, 71%), most commonly pregnancy among females (537/852, 63%) and transfusion among males (180/348, 52%). When multiple potential sources were included, males were more likely than females to have a history of transfusion (235/348 [68%] vs. 149/852 [17%], p < .0001) and confirmed or suspected intravenous drug abuse (100/348 [29%] vs. 138/852 [16%], p < .0001). Among females with a history of pregnancy, 119/718 (17%) had healthcare access issues, 120/718 (17%) had pregnancy in a country where they may not have received RhIg, and 21/718 (3%) refused RhIg. Among patients with a history of transfusion, males were more likely than females to have received RhD‐positive red blood cells or whole blood (143/235 [61%] vs. 30/149 [20%], p < .0001) and/or platelets (84/235 [36%] vs. 19/149 [13%], p < .0001). Discussion Pregnancy was the most frequently identified potential source of RhD alloimmunization among females. Transfusion was most frequent in males. Intravenous drug abuse as a common potential source among patients with RhD alloimmunization merits further study.

AbstractBackgroundTrauma remains the leading cause of pediatric mortality in the United States. Although use of massive transfusion protocols (MTPs) in this population is widespread, optimal pediatric resuscitation is not well established. We sought to assess contemporary pediatric MTP practice in the United States.Study Design and MethodsA web‐based survey was designed by the Association for the Advancement of Blood & Biotherapies (AABB) Pediatric Transfusion Medicine Subsection and distributed to select American College of Surgeons (ACS) Level I Verified pediatric trauma centers. The survey assessed current MTP policy, implementation, and recent changes in practice.ResultsResponse rate was 55% (22/40). Almost half of the respondents were from the South. The median RBC:plasma ratio was 1 (interquartile range 1–1.5). Protocolized fibrinogen supplementation was common while integration of antifibrinolytic therapy into MTPs was infrequent. Viscoelastic testing (VET) was available at most sites, 71% (15/21, one site did not respond), and was generally utilized on an ad‐hoc basis. Roughly, a third of sites had changed their MTP in the past 3 years due to blood supply issues, and about a third reported having group O Whole Blood on‐site.ConclusionMTP practice is similar throughout the United States. Though fibrinogen supplementation is common—other emerging interventions such as antifibrinolytic therapy or utilization of routine viscoelastic testing—are not widespread. Pediatric transfusion medicine experts must continue to follow practice change, as contemporary large trials begin to characterize new supportive modalities to optimize resuscitation in pediatric trauma patients.

AbstractBackground and ObjectivesConvalescent COVID‐19 plasma (CCP) was developed and used worldwide as a treatment option by supplying passive immunity. Adult studies suggest administering high‐titer CCP early in the disease course of patients who are expected to be antibody‐negative; however, pediatric experience is limited. We created a multi‐institutional registry to characterize pediatric patients (<18 years) who received CCP and to assess the safety of this intervention.MethodsA REDCap survey was distributed. The registry collected de‐identified data including demographic information (age, gender, and underlying conditions), COVID‐19 disease features and concurrent treatments, CCP transfusion and safety events, and therapy response.ResultsNinety‐five children received CCP: 90 inpatients and 5 outpatients, with a median age of 10.2 years (range 0–17.9). They were predominantly Latino/Hispanic and White. The most frequent underlying medical conditions were chronic respiratory disease, immunosuppression, obesity, and genetic syndromes. CCP was primarily given as a treatment (95%) rather than prophylaxis (5%). Median total plasma dose administered and transfusion rates were 5.0 ml/kg and 2.6 ml/kg/h, respectively. The transfusions were well‐tolerated, with 3 in 115 transfusions reporting mild reactions. No serious adverse events were reported. Severity scores decreased significantly 7 days after CCP transfusion or at discharge. Eighty‐five patients (94.4%) survived to hospital discharge. All five outpatients survived to 60 days.ConclusionsCCP was found to be safe and well‐tolerated in children. CCP was frequently given concurrently with other COVID‐19‐directed treatments with improvement in clinical severity scores ≥7 days after CCP, but efficacy could not be evaluated in this study.

AbstractImportanceNeuromyelitis optica/neuromyelitis optica spectrum disorder patients' response to therapeutic plasma exchange (TPE) is currently incompletely characterized.ObjectiveOur study aims to understand the clinical status improvement of neuromyelitis optica/neuromyelitis optica spectrum disorder patients treated with TPE.Design, Setting, and ParticipantsThis is a multicenter retrospective study conducted between 1 January 2003 and 31 July 2017 at 13 US hospitals performing apheresis procedures. Subjects studied were diagnosed with neuromyelitis optica/neuromyelitis optica spectrum disorder who received TPE during presentation with acute disease.Main Outcomes and MeasuresThe primary outcome was clinical status improvement in patients treated with TPE. Secondary measures were procedural and patient characteristics associated with response to treatment.ResultsWe evaluated 114 patients from 13 institutions. There was a female predilection. The largest ethnic group affected was non‐Hispanic Caucasian. The average age of diagnosis was 43.1 years. The average time to diagnosis was 3.1 years. On average, five procedures were performed during each treatment series. The most commonly performed plasma volume exchange was 1.0 to 1.25 using 5% albumin as replacement fluid. Most patients (52%) did not require an additional course of TPE and noted “mild” to “moderate” clinical status improvement. Maximal symptom improvement appeared by the fourth or fifth TPE treatment.Conclusion and RelevanceTPE improved the clinical status of patients. Adults responded more favorably than children. Procedural characteristics, including number of TPEs, plasma volume exchanged, and replacement fluid used, were similar between institutions. TPE was well‐tolerated and had a low severe adverse event profile.