Transfusion最新文献

Background: Storage of packed red blood cells (RBCs) for transfusion leads to biochemical and morphological changes, increasing hemolysis risk. Urate levels in blood bags at donation contribute to the molecular heterogeneity and hemolytic propensity of stored RBCs. However, studies to date have been underpowered to investigate at scale the contribution of donor demographics and genetics to the heterogeneity in urate levels across donations.

Study design and methods: Urate levels were measured in 13,091 RBC units from the REDS study. Characteristics tested included hemolysis parameters (spontaneous, osmotic, oxidative) at storage end and post-transfusion hemoglobin (Hb) increments in recipients. Donor demographics, urate levels, and genetic variants were analyzed for associations with these outcomes.

Results: Elevated urate levels were linked to male sex, older age, high BMI, and Asian descent. Units with high urate levels exhibited increased spontaneous and osmotic hemolysis, while oxidative hemolysis was unaffected. Genetic variants in SLC2A9 (V282I) and ABCG2 (Q141K) were strongly associated with elevated urate, particularly in Asian donors. Post-transfusion analyses revealed that units from female donors carrying these variants were associated with reduced Hb increments, with up to a 31% reduction in efficacy. This effect was not observed in male donors.

Discussion: RBC urate levels and genetic traits significantly impact storage quality and transfusion outcomes. These findings highlight the importance of donor molecular characteristics for optimizing transfusion strategies. Moreover, genetic and metabolic insights may inform donor recruitment efforts, providing health feedback to volunteers while ensuring effective transfusion products.

Background: Prior studies have evaluated transfusion recipient variables impacting red blood cell (RBC) alloimmunization, but few focused on potentially modifiable blood donor or blood component variables.

Study design and methods: Data from the Recipient Epidemiology and Donor Evaluation Study (REDS)-III, which links donor, component, and patient data in an integrated database, were accessed. For any given RBC unit with sufficient blood donor and component data, we determined if the transfusion recipient experienced a new RBC alloimmunization event ("case") within 16 weeks of the transfusion or not ("control"). Recipient diagnoses were included in the case-control matching algorithm.

Results: A total of 2676 cases were matched with 10,160 controls. In a multivariate conditional logistic regression analysis, recipients who received an RBC unit from donors with a different ABO group had a higher risk of alloimmunization (OR 1.60, 95% CI: 1.35-1.89, p < .001). Likewise, recipients who received RBCs from older donors had a higher risk of RBC alloimmunization (OR 1.01 per year of age, 95% CI: 1.00-1.01, p < .001). Irradiated RBCs were associated with a decreased risk of RBC alloimmunization in transfusion recipients (OR 0.52, 95% CI: 0.46-0.59, p < .001), though a sub-analysis of RBCs transfused to people with sickle cell disease showed no such association (p = .75). Recipients who received RBCs stored for a longer duration also had a lower risk (OR 0.99 per day of storage, 95% CI: 0.99-0.99, p < .001) of alloimmunization.

Discussion: This case-control study identified donor and component variables associated with recipient RBC alloantibody formation. Future mechanistic studies exploring these associations are warranted.

Background: Neonates with congenital anomalies frequently require perioperative allogeneic red blood cell (RBC) transfusion. Whole cord blood for autologous transfusion to neonates may provide an alternative RBC source, but whether sufficient volumes can be collected after delayed cord clamping to reduce allogeneic RBC requirements is unknown.

Study design and methods: Inclusion criteria were mothers delivering a viable infant >34 weeks' gestation. Sterile cord blood collection from the umbilical cord was performed at delivery as per routine obstetric indications. During storage at 4°C, we performed weekly blood gases. Blood culture, complete blood count, and hemolysis tests were performed at baseline and day 21. We compared the whole cord blood volume collected with each infant's allogeneic transfusion requirements.

Results: 54 collection attempts yielded 49 collections with a mean volume of 54.1 mL (±20.3) after median delayed cord clamping of 46 seconds (IQR 12.0, 60.0). Among 39 blood cultures obtained, 3 grew organisms after vaginal delivery (3/27, 11.0% vs. 0/12, 0% cesarean delivery, p = .54). Hemolysis was stable during storage (baseline vs. day 21, median [IQR], 0.7% [0.4%-0.9%] vs. 0.7% [0.6%-1.1%], p = .08).

Conclusions: Whole cord blood collection following delayed cord clamping was feasible, with volumes equal to 16.7 mL/kg, or one transfusion. Hemolysis was low, and although potassium increased during storage, it was consistent with patterns observed with adult donor stored whole blood. There were no positive blood cultures from collections during cesarean deliveries. Studies are needed to determine whether whole cord blood transfusions improve patient outcomes.

Background: We aimed to investigate if iron deficiency was associated with infection susceptibility in a large cohort of healthy individuals.

Study design and methods: The Danish Blood Donor Study is a national ongoing prospective study of blood donors. We included 94,628 donors with 338,290 ferritin measurements from March 2010 to October 2022. We performed sex-stratified multivariable Cox regression to estimate the risk of infection for iron-deficient donors compared with iron-replete donors. Infection was defined as either a filled prescription of antibiotics registered in the Danish National Prescription Registry (NPR), or a hospital contact with infection registered in the Danish National Patient Registry (DNPR).

Results: Iron deficiency was associated with an overall increased risk of infection (defined as prescriptions of antibiotics) for women (hazard ratio [HR] 1.08, 95% confidence interval [CI] 1.02-1.15). Subgroup analyses showed an increased risk of respiratory tract infections (HR 1.16, 95% CI 1.05-1.28) and urinary tract infections (HR 1.16, 95% CI 1.04-1.29). Iron deficiency was not associated with overall risk of infection for men (HR 1.02, 95% CI 0.82-1.28). For both men and women, no association was found between iron deficiency and hospital contacts for infections.

Conclusion: Iron deficiency was associated with an increased risk of infection in female blood donors. However, effect sizes were small, and there was no association between iron deficiency and hospital contacts for infection. Consequently, risk of infection should not be considered an apprehension regarding blood donation. These findings support the role of iron in immune function and monitorization of iron stores in female blood donors.

Background: Although alloimmunization risk of pathogen-reduced (PR) platelets has been studied, the risk has not been reported with PR red blood cells (RBCs).

Study design and methods: In a Phase III, randomized, controlled trial (Red Cell Pathogen Inactivation), cardiac or thoracic-aorta surgery patients were randomized to transfusion with amustaline/glutathione PR versus conventional RBCs. Pre-transfusion and Day 28 samples were evaluated for Human leukocyte antigen (HLA) Class I and Class II antibodies at low, medium, and high cutoff values.

Results: The HLA alloimmunization analysis included 114 participants (53% female) in the PR and 113 (51% female) in the conventional RBC arms. In a modified intention-to-treat analysis, 13.7% (N = 29) and 7.2% (N = 15) developed new high-level HLA Class I or Class II antibodies, respectively; however, there was no signal that PR-RBCs affected the rate of HLA Class I (odds ratio (OR) 1.3 [95% confidence interval (CI) 0.62-2.9]) or Class II antibody formation (OR 0.99 [95% CI 0.35-2.8]). Female transfusion recipients had higher risk of developing new high-level HLA Class I antibodies (OR 12.0 [95% CI 3.5-40.9]) and Class II antibodies (OR 5.0 [95% CI 1.4-17]). The mean number of RBC (5.5 vs. 3.6 units, p = 0.018) and platelet (1.8 vs. 1.1 units, p = 0.043) transfusions was higher in subjects with new high-level HLA Class II antibodies.

Discussion: Receipt of amustaline/glutathione PR-RBC units did not affect HLA alloimmunization risk. Female sex and number of RBC and platelet transfusions were risk factors for the development of new high-level HLA Class I and Class II antibodies.

Background: Allocating incompatible platelet components to avoid product wastage must be balanced against the risk of reduced efficacy and adverse outcomes. The impact of platelet compatibility in association with product irradiation or pathogen reduction is unknown. This study aims to determine the combined and independent impact of platelet compatibility and component modification on transfusion reaction rate.

Study design and methods: A retrospective review of all adult platelet transfusions from 2020 to 2022 was performed, including all reported reactions. Logistic regression was performed to evaluate the significance of ABO compatibility and unit modification for reaction rate.

Results: Out of 21,330 transfusions to 3450 patients, 285 (1.33%) reactions were reported and 178 (0.83%) were diagnosed as related to transfusion, predominantly febrile nonhemolytic (n = 59) and allergic (n = 102). The compatibility of transfusion was 67.7% ABO identical, 13.8% ABO minor incompatible, 17.2% ABO major incompatible, and 1.4% ABO bidirectionally incompatible. Irradiated, unmodified, and pathogen-reduced single-donor platelets were transfused in 70.9%, 21.8%, and 7.3% of cases, respectively. Univariable regression demonstrated increased odds of reaction for major incompatibility vs. ABO identical (OR: 1.92; 95% CI: 1.36-2.71) and irradiated vs. unmodified (OR: 2.34; 95% CI: 1.45-3.91), which were confirmed by multivariable analysis. The effect of compatibility and unit modification were independent in all analyses.

Conclusions: The results demonstrate a trend of increasing reaction rate associated with major incompatibility and product irradiation. This study provides additional data to inform institutional policies guiding product selection for individual patients.

Background: Effective hemorrhage protocols prioritize immediate hemostatic resuscitation to manage hemorrhagic shock. Prehospital resuscitation using blood products, such as whole blood or alternatively dried plasma in its absence, has the potential to improve outcomes in hemorrhagic shock patients. However, integrating blood products into prehospital care poses substantial logistical challenges due to issues with storage, transport, and administration in field environments.

Study design and methods: We utilized hemostatic assays and advanced biophysical techniques, such as calorimetry, infrared spectoscopy, dynamic light scattering, and biolayer interferometry, to compare the functional and structural properties of freeze-dried plasma (FDP; OctaplasLG Powder, Octapharma AB) with those of fresh plasma controls.

Results: Hemostatic characterization of FDP revealed that clot formation properties and coagulation parameters were largely comparable to fresh plasma controls, with some variations observed in Von Willebrand factor-ADAMTS13 axis and fibrinolysis. No change to moisture content of FDP (~1% water content) was observed after 6-month storage at ambient conditions. Biophysical analyses of FDP during transfusion demonstrated spontaneous exothermic mixing of FDP in plasma, a dilution effect from saline, as well as comparable stability to plasma controls. Quantification of ligand-binding affinities of platelet receptors activated GPIIbIIIa and GPIbα showed comparable binding properties to plasma controls.

Conclusion: Our results show that FDP exhibits hemostatic functionality and protein stability on par with fresh plasma, as assessed by novel, highly sensitive techniques. FDP therefore represents a viable alternative to conventional plasma in damage control resuscitation, offering significant logistical and storage advantages for prehospital and remote applications, especially in scenarios where whole blood is unavailable.

Background: Detection of alloantibodies associated with the JK system may be tricky. They are nevertheless associated with transfusion reactions and their detection is crucial.

Study design and methods: Retrospectively and over a period of 7 years, we compared the results obtained using two different assays for antibody detection. We performed antibody detection testing with solid-phase red cell adherence (SPRCA). If positive, the antibody identification was carried out with the SPRCA and confirmed with the gel method in Coombs medium. In case of discrepant results occurring in recently transfused patients, we investigated these patients during the post-transfusion period.

Results: Fifty-five patients with anti-JK1 or anti-JK2 were identified out of which 41 were further analyzed. Both techniques clearly identified 10 alloantibodies. In 22 cases, the alloantibody identified by SPRCA was not observed with the gel method because of negative detection tests. In one case, none of the techniques identified the alloantibody and in 8 cases, the final result was inconclusive (1/41 with the SPRCA and 8/41 with the gel method). Two patients having a highly probable delayed hemolytic transfusion reaction (DHTR) were identified among the discrepant results. For both cases, anti-JK2 was clearly identified by the SPRCA but showed inconclusive reactions with the gel method.

Discussion: This study shows that in 29 out of 41 cases, the anti-JK1 or anti-JK2 identified with the SPRCA method were not with the gel method in Coombs medium. Eleven cases (11/29) were clinically significant and among them, 4 likely DHTRs and 2 highly probable DHTRs occurred.

Background: Ethylenediamine tetraacetate/glycine acid (EGA) and chloroquine diphosphate (CDP) are used in transfusion testing to dissociate IgG antibodies from red blood cells (RBCs). However, the ability of these reagents to dissociate IgM antibodies sensitized to RBCs has not been comprehensively elucidated. We investigated whether EGA and CDP could dissociate cold-reactive antibodies from RBCs and their effect on RBCs after dissociation treatment.

Study design and methods: Cold-reactive antibody-sensitized RBC samples were prepared by mixing group A RBCs and group B plasma and treated with EGA, CDP, and dithiothreitol (DTT). Before and after the dissociation treatment, changes in the agglutination of these RBCs were assessed using the test tube method. Flow cytometric analysis was used to confirm the nature of antibodies bound to RBCs. Additionally, RBC morphology was evaluated using scanning electron microscopy. This study utilized off-label use of EGA and CDP.

Results: Flow cytometric analysis showed that antibodies sensitized to RBCs were mainly IgM antibodies. After antibody dissociation, agglutination disappeared in the EGA-treated samples to the same degree as in the DTT-treated samples. However, IgM antibodies remained in the CDP-treated samples. Regarding RBC morphology, RBC surface appeared coarser in both EGA- and CDP-treated samples, and RBC area was significantly smaller in the CDP-treated samples than in the EGA-treated samples.

Discussion: EGA could dissociate cold-reactive antibodies, whereas CDP had a higher residual antibody content. This difference in dissociation ability appears to correlate with the antibody pH of the dissociation reagent. EGA treatment may be useful in cases of sensitization by high-titer cold-reactive antibodies.