Transfusion最新文献

Background: ABO blood type is critically important for blood transfusion and organ transplantation. Blood group reactive glycan-binding proteins are used as reagents in clinical and research laboratories to detect the glycan epitopes that define ABO blood type. The glycan specificities of these clinically used reagents are not well defined.

Methods and materials: We used a glycan microarray to evaluate the specificities of a series of ABO(H) glycan-binding proteins: Ulex europaeus agglutinin I (UEA-I), Helix pomatia agglutinin (HPA), Dolichos biflorus agglutinin (DBA), anti-A antibody, and anti-B antibody.

Results: UEA-I binds many but not all H antigens and binds to some glycans that do not have the H antigen. HPA binds to terminal α-linked N-acetylgalactosamine, as found in the A antigen, but also to glycans with other terminal monosaccharides. DBA shows comparatively low binding to A antigens and binds more strongly to GM2 ganglioside sugar and Forssman antigens. Anti-A and anti-B monoclonal antibodies that are used for clinical ABO blood type determination demonstrate superior specificity compared to the lectins.

Conclusions: This glycan microarray data expands our understanding of the glycan specificities of commonly used ABO blood group binding reagents and indicates that caution should be used in interpretations of their binding.

Background: Activation of complement protein C3 generally enhances antibody responses and C3-null mice have decreased antibody-based immunity. Mener et al. have reported a paradoxical suppressor function for C3 in alloimmunization to transfused RBCs as alloantibodies are increased in C3-null mice. Moreover, C3 regulated the CD4⁺ T cell dependence of the immune response. However, the C3-null mice used were on a mixed B6/129 genetic background. We have previously reported that 129 mice have significantly higher alloimmune responses to RBC transfusion and we mapped a genetic locus that contains C3 (amongst other genes). Given the surprising nature of Mener et al.'s findings and the potential confounding from 129 genetic elements, it is a necessary part of scientific rigor to suspect that contaminating 129 elements rather than the deletion of C3 caused the observed biology.

Methods: We used CRISPR/Cas9 to generate a new C3-null mouse (C3Cr-KO) directly in B6 mice lacking any 129 genetic elements. B6 and C3Cr-KO mice were transfused with KEL-K2_med RBCs with or without CD4⁺ T cell depletion and serum α-KEL IgM and Igs were quantified by crossmatch.

Results: Identical to the findings of Mener et al., alloimmunization was increased in C3Cr-KO mice compared to wild-type B6 mice and CD4⁺T cell dependence of the alloimmune response was reversed.

Conclusions: The current findings eliminate a common confounder present in murine knockout systems that has caused erroneous conclusions in other settings. Both the conclusion that the presence of the C3 gene decreases RBC alloimmunization and regulates CD4⁺ T cell dependence was confirmed.

Background: Red blood cell transfusions (RBCT) are essential and lifesaving for preterm infants who suffer from physiological and iatrogenic anemia. Phlebotomy-induced anemia (PIA) in neonatal murine pups has been linked to hippocampal inflammation; however, the impact of repletion with packed RBCT has not been evaluated despite its known advantages in relieving anemia and restoring oxygen-carrying capacity.

Study design and methods: C57BL/6 pups underwent PIA, and FVB-donor-derived packed RBCs were administered retro-orbitally on postnatal(P) day 11. On P12, whole-brain protein lysate was analyzed for cytokines and chemokines using a Multiplex array. Endotoxin was measured using the LAL test. Immunofluorescence and flow cytometry were performed to characterize microglia and recruited myeloid cells. The key inflammatory functional genes were measured by qRT-PCR.

Results: Inflammatory cytokines and chemokines were significantly elevated in the anemic brains compared to naïve controls and markedly higher in anemic-transfused brains compared to transfused controls, resulting in anemia-transfusion-associated brain inflammation (ATBI). Anemic and anemic-transfused mouse groups had increased BBB permeability, and brain tissue had elevated levels of endotoxin with a loss of ramified-structured microglia. ATBI was associated with the recruitment of CD11b^hiCD45⁺Ly6C⁺ monocytes in the brains of anemic-transfused pups and showed a hyperinflammatory phenotype compared to tissue-resident microglial cells (CD45^-CD11b^hi) and revealed suppression of genes involved in myelination, neuronal cell proliferation, and developmental processes.

Conclusion: We report that PIA causes early brain inflammation and RBCT leads to the recruitment of circulating monocytes to the anemic brain, thus contributing to a chronic hyperinflammatory response with transcriptional changes in genes associated with brain function.

Background: The Kell null (K₀) is a rare phenotype characterized by the absence of all Kell blood group antigens. Individuals with K₀ are often identified after developing anti-Ku, an antibody associated with hemolytic transfusion reactions (HTR) and hemolytic disease of the fetus and newborn (HDFN). Transfusion management in this population is particularly challenging as compatible blood is difficult to find. It is crucial to adopt safe and reliable treatments for preoperative blood management.

Study design and methods: We describe a K₀ woman with potent Ku alloantibody preparing for surgery. Kell antigen typing and titers of anti-Ku were detected by standard serologic techniques. Polymerase chain reaction (PCR) and DNA sequencing of the KEL coding region were performed on her genomic DNA. Therapeutic plasma exchange (TPE) was initiated for five sessions to reduce the high anti-Ku titers before surgery.

Results: The red blood cells (RBCs) phenotype of the Kell blood group was identified as K- k-; Kp(a- b-). DNA sequence analysis revealed the patient was homozygous for a nucleotide deletion, NM_000420.3:c.855delT (p.L286*) in exon 8 of the KEL gene. After TPE, the anti-Ku titers decreased from 1:1600 to 1:400. A rebound phenomenon was noted during the procedures.

Discussion: We identified a novel homozygous KEL variant causing K₀ phenotype in a Chinese woman with Ku alloimmunization. TPE proved to be effective for decreasing anti-Ku titers. However, the rebound of antibodies should be considered when using TPE to decrease the antibody titers. This report demonstrates a new attempt in preoperative transfusion management for patients with rare alloantibodies.

Background: Rh immune globulin (RhIG) is used to prevent D alloimmunization and reduce the risk of hemolytic disease of the fetus and newborn (HDFN). Its use has been expanded to include immunoprophylaxis after D-incompatible transfusions. In the United States, a protracted RhIG shortage began in 2023. The AABB (Association for the Advancement of Blood & Biotherapies) Clinical Hemotherapy Subsection created a survey to assess RhIG usage patterns during this shortage.

Methods: A survey was developed and electronically distributed to AABB-accredited institutions. The number of responses was tallied. Frequencies were calculated, and free text comments were categorized.

Results: A total of 112 responses (13.7%) were received from all regions of the United States. While 6.2% (6/97) of respondents noticed increased RhIG usage, 70.0% (56/80) experienced a shortage of RhIG. The most common indication reported for RhIG use was D-negative pregnant patients carrying a D-unknown or D-positive fetus/neonate. Some respondents also permitted RhIG use in D-negative adult males and females outside of childbearing age following D-incompatible transfusion. The most common institutional responses to the shortage were to: formally monitor RhIG inventory (n = 37), add (n = 34)/switch (n = 24) manufacturers, and redistribute RhIG between facilities (n = 22). Few respondents (n = 7) limited or discontinued RhIG use in non-obstetric patients.

Conclusions: While the majority of survey respondents were affected by the RhIG shortage, transfusion services still allowed RhIG to be issued outside of obstetric care. Given that RhIG is a limited resource and its intended goal is to reduce anti-D HDFN, more effective management of RhIG utilization is needed.

Background: Transfusion practices among intensive care unit (ICU) patients with sepsis vary widely. While restrictive hemoglobin thresholds for red blood cell (RBC) transfusion are well studied, the indications and thresholds for platelet and plasma transfusions remain uncertain.

Methods: We performed a sepsis-specific sub-analysis of the International Point Prevalence Study of Intensive Care Unit Transfusion Practices, a prospective, multicenter, observational study capturing all adult ICU admissions during four pre-scheduled weeks between March 2019 and October 2022. Patients admitted with sepsis or septic shock, or who developed sepsis during their ICU stay, were included. We recorded demographics, daily laboratory values, and transfusion triggers. Primary endpoints were the proportions of patients receiving RBCs, platelets, or plasma; secondary endpoints were indications, pre-transfusion thresholds, and blood loss.

Results: Among 3643 screened patients, 799 (22%) fulfilled sepsis criteria; within this subgroup, 317 (40%) received at least one blood component. RBCs were transfused in 269 patients (34%), primarily to address anemia or hemodynamic instability, at a mean pre-transfusion hemoglobin of 7.5 ± 1.4 g/dL, consistent with restrictive practice. Platelets were given to 78 patients (10%) for prophylaxis or active bleeding at a median count of 26 × 10⁹ cells/L (interquartile range 16-51 × 10⁹ cells/L). Plasma was administered to 108 patients (14%), half for bleeding control and half for non-bleeding indications.

Conclusions: This largest international snapshot of septic ICU transfusion practices confirms adherence to restrictive RBC thresholds but reveals substantial variability in platelet and plasma use. These findings underscore the need for targeted trials to refine transfusion guidelines in sepsis.