Transfusion最新文献

Background: IgG4 monoclonal anti-CD47 for cancer immunotherapy resulted in anemia necessitating red cell (RBC) transfusions. Although the antibody readily binds to CD47 on RBCs, the mechanism underlying the anemia associated with IgG4 is poorly understood. We investigated samples from patients receiving Hu5F9-G4 (magrolimab) with positive reactivity in compatibility tests using a monocyte-monolayer assay (MMA).

Study design and methods: For RBC opsonization, patient plasma was diluted to avoid direct agglutination and to give a 4+ indirect antiglobulin test (IAT) and >10³ mean fluorescent intensity (MFI) by flow cytometry. Fcγ receptor blocking used F(ab')₂ antibodies. Antibody-dependent cellular cytotoxicity (ADCC) used purified natural killer (NK) cells. Recombinant IgG4 anti-K and polyclonal anti-D were tested by MMA concurrent with blocking of CD47 with a deglycosylated antibody.

Results: Five of six samples showed significant erythrophagocytosis (phagocytosis index [PI] = 20-60; PI > 5 clinically significant) with the exception having 30-fold lower MFI. Phagocytosis was not increased in the presence of complement. Fcγ receptor blocking showed FcγRI and FcγRIIa were involved but not FcγRIIIa, supported by negative results when tested for NK ADCC. IgG4 anti-K also showed significant erythrophagocytosis (PI = 30). Blocking of CD47 increased phagocytosis, 1.7 to 3.9-fold, respectively, of RBCs opsonized with IgG4 anti-K or polyclonal anti-D.

Conclusion: IgG4 RBC antibodies, generally not considered clinically significant for transfusion, can result in erythrophagocytosis providing an explanation for anemia related to anti-CD47 mediated by FcγRI and FcγRIIa. Enhanced phagocytosis of alloantibody-coated RBCs with concurrent blocking CD47 suggests potential for enhanced complications for patients who develop RBC alloantibodies while receiving cancer therapies targeting CD47.

Background: Transfusion-related acute lung injury (TRALI) is a clinical condition characterized by acute non-cardiogenic pulmonary edema during or after transfusion. Despite several mitigation strategies, TRALI remains a leading cause of transfusion-related deaths. Tests on blood donors involved in TRALI, apart from leukocyte/endothelial reactive alloantibodies, can also reveal the presence of neutrophil autoantibodies. Here, we ask the question whether these autoantibodies could play a role in the development of TRALI.

Materials and methods: Sera (n = 15) from donors involved in TRALI and not containing alloantibodies against human neutrophil antigens (HNAs) and human leukocyte antigens (HLAs) were collected if their serological characterization was suggestive for the presence of neutrophil-reactive autoantibodies. Sera (n = 12) were suitable for the study. Their ability to bind complement, to activate neutrophils, and to disrupt the endothelial barrier using albumin influx through an endothelial monolayer in a transwell chamber in the presence and absence of neutrophils was investigated.

Results: None of the AIN sera, but 2/12 TRALI sera, induced reactive oxygen species (ROS) in neutrophils. Both of these TRALI sera induced endothelial barrier permeability in the presence, but not in the absence, of neutrophils. These two sera did not activate complement.

Conclusion: Autoantibodies against neutrophils present in transfused blood components appear to be capable of contributing to TRALI in selected but not in all investigated cases, based on their ability to activate neutrophil ROS and induce endothelial cell permeability in vitro. Further analysis is required to understand the potential functional effects of neutrophil autoantibodies in TRALI.

Background: Plasma donation is critical for the production of plasma-derived medicinal products, yet donor recruitment and retention remains challenging within a volunteer system. This paper explores deterrents to plasma donation among current plasma donors, whole-blood donors, lapsed whole-blood donors, and non-donors in the United Kingdom, and self-reported post-donation symptoms in plasma donors.

Study design and methods: An online survey of the UK general public (current and lapsed blood donors, and non-donors: n = 2861) and English current plasma donors (n = 448), and one-to-one interviews (n = 25) with plasma donors were conducted. Participants identified deterrents to plasma donation, and plasma donors described post-donation symptoms.

Results: Plasma donors reported distinct deterrents around time constraints and ineligibility. There were differences by donor status. Blood, plasma, and non-donors all report pain, lack of travel compensation, involvement of private companies and incentives as concerns. Lack of awareness was salient for non-donors and blood donors, while non-donors had concerns about neurodiversity and donors about incentives to change. Being deferred on the day, described as an embarrassing "walk of shame," was a unique deterrent to plasma donors. 11.8% (53/488) of plasma donors reported symptoms of feeling ill after donation. Of these, 73% (n = 38) occurred and were managed in center (e.g., feeling faint, bruising) and 25% (n = 13) outside of the center (e.g., feeling faint) and managed by the donor (2% other).

Discussion: Different profiles of deterrents were observed for plasma donors compared to whole blood and non-donors. Recommendations for the recruitment and retention of plasma donors in England are discussed.

Background: Low hemoglobin (Hb) is the leading cause of blood donor deferral yet mean Hb values are seldom examined as sentinel indicators of changes in donor recruitment, assessment, or testing. Case in point, following unexplained improvement in these parameters, U.S. blood centers observed a sharp rise in low-Hb deferrals after the 2024 introduction of a new international calibrator for some fingerstick hemoglobinometers.

Methods: We retrospectively analyzed 15 years (2010-2024) of allogeneic donor data from a national blood center. Mean donor Hb and low-Hb deferral rates were trended overall and by sex, cognizant of temporal practices affecting values like a ferritin testing program, the 2016 male Hb cutoff adjustment, and acceptance of allogeneic donors with testosterone-associated polycythemia.

Results: Among >11 million presentations (49.8% female), mean Hb values rose progressively from 2016 through 2023, correlating with a suspected gradual positive bias from a degrading hemoglobinometry standard. Female low-Hb deferrals declined from 12.2% (2016) to 7.7% (2023) before rebounding to 2016 levels in 2024 following recalibration. Male mean Hb trends were additionally influenced by increasing testosterone use in the donor base and the higher 13.0 g/dL Hb cutoff. Ferritin-based deferral programs temporarily raised mean Hb and reduced low-Hb deferrals, which reversed when suspended.

Discussion: Hemoglobinometer calibration drift, a ferritin testing policy, and donor testosterone use together shaped long-term donor Hb trends. Surveillance of mean donor Hb should be treated as a sentinel metric, and unexpected declines and increases in related deferral rates warrant the same scrutiny to protect both donors and blood availability.

Introduction: SARS-CoV-2 infection is associated with hypercoagulability in patients with Coronavirus disease (COVID-19). We used a vein-to-vein database to examine the impact of transfusion of plasma units from blood donors with recent SARS-CoV-2 infection.

Study design and methods: We linked donor SARS-CoV-2 serology data with plasma transfusions occurring between 6/1/2020 and 3/31/2022. Using multivariable regression, we examined changes in the international normalized ratio (INR) and subsequent transfusion requirements following plasma transfusion relative to the timing of donor SARS-CoV-2 nucleocapsid antibody (anti-N Ab) positivity.

Results: We identified 2350 adults who received 5397 plasma units with donor SARS-CoV-2 serology data as part of 3721 plasma transfusion events. 8.1% (436/5397) of plasma units were from anti-N Ab positive donors, and median time from index seropositivity to donation was 89 days (interquartile range [IQR] 0-210). In recipients of plasma units from recently SARS-CoV-2 infected donors (<120 days), the adjusted odds of a 0.25 per unit lowering of the INR were increased (aOR 1.6 [1.1-2.5]; p = .03) and the odds of additional plasma transfusions within 24 h were decreased (aOR 0.6 [0.4-0.9]; p = .04).

Conclusion: Recipients of plasma units from blood donors with recent SARS-CoV-2 infection were more likely to have post-transfusion reductions in the INR and less likely to require additional plasma transfusions.

Introduction: The immunomodulatory consequences of blood transfusion, known as transfusion-related immune modulation (TRIM), are often not captured by hemovigilance systems. Changes to blood product manufacturing processes may impact patient outcomes.

Design and methods: We conducted a retrospective study of hospitalized adults (≥18 years) in Hamilton, ON, who received ≥1 red blood cell (RBC) transfusion(s) between 2010 and 2014. Primary outcome was in hospital mortality; TRIM outcomes included respiratory failure, organ dysfunction, and sepsis. We evaluated outcomes before and after the change made by Canadian Blood Services (2012) to consolidate manufacturing of blood products in Ontario. Exclusions included autologous, washed, or deglycerolized RBC transfusions, RBCs manufactured outside select regional sites, or patients who received both pre-/post-consolidation RBCs. Data was obtained from the TRUST database. Logistic regression adjusted for key covariates.

Results: A total of 9871 pre- and 7871 post-consolidation patients met inclusion criteria. Multivariate analysis demonstrated no change in in-hospital mortality (odds ratio [OR] 1.00, 95% confidence interval [CI] 0.89-1.14, p = 0.95), respiratory failure (OR 0.83, CI 0.65-1.06, p = 0.14) or organ dysfunction (OR 0.95, 95% CI 0.84-1.08, p = 0.42) comparing post to pre-consolidation. However, hospital-onset sepsis was lower post-consolidation (OR 0.59, 95% CI 0.48-0.73, p < 0.001).

Conclusions: Consolidation of blood production in Ontario was not associated with changes in rates of in-hospital mortality, respiratory failure, or organ dysfunction among transfusion recipients, but may be associated with a lower risk of sepsis. TRIM and the clinical impacts of changes to blood processing require further study.

Background: Cell and gene therapies (CGTs) represent a paradigm shift in modern medicine, offering targeted and potentially curative options for complex and rare diseases. Their integration into health-system pharmacy practice requires alignment with the medication-use process to ensure safety, efficacy, and compliance.

Objective: To propose a practical framework for integrating CGTs into health-system pharmacy workflows, while addressing clinical, operational, and financial considerations.

Summary: The framework encompasses four domains: (1) evaluation-strategic assessment of pipeline therapies, including clinical, operational, and financial readiness; (2) clinical integration-formulary review, electronic medical record configuration, clinical pathways, and standard operating procedures development; (3) operational pharmacy integration-establishing infrastructure for receipt, storage, handling, and dispensing, supported by training and process improvement; and (4) financial integration-implementing reimbursement strategies, payment workflows, and budgeting to mitigate financial risk. These recommendations draw on the institutional experience of the authors and emerging standards from professional organizations.

Conclusion: Proactive planning and interdisciplinary collaboration are essential for successful CGT implementation. Health-system pharmacists are uniquely positioned to lead these efforts, ensuring patient safety, operational efficiency, and financial sustainability as advanced therapeutics reshape the healthcare landscape.