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22 pages, 13067 KiB  
Article
Engineering Marrow-Mimetic Hydrogel Platforms Enhance Erythropoiesis: A Mechanobiology-Driven Approach for Transfusion Red Blood Cell Production
by Qinqin Yang, Runjin Liu and Xiang Wang
Gels 2025, 11(8), 594; https://doi.org/10.3390/gels11080594 - 31 Jul 2025
Viewed by 136
Abstract
Red blood cell (RBC) production from bone marrow hematopoietic stem cells (BMHSCs) in vitro overlooks the mechanical signals of the bone marrow niche and overly relies on growth factors. Considering that the fate of hematopoietic stem cells (HSCs) is determined by the natural [...] Read more.
Red blood cell (RBC) production from bone marrow hematopoietic stem cells (BMHSCs) in vitro overlooks the mechanical signals of the bone marrow niche and overly relies on growth factors. Considering that the fate of hematopoietic stem cells (HSCs) is determined by the natural bone marrow microenvironment, differences in mechanical microenvironments provide a reference for the regulation of HSC differentiation. This study seek to reveal the role of mechanobiology cues in erythropoiesis and provide a new perspective for the design of in vitro erythropoiesis platforms. The hydrogel platforms we designed simulate the stiffness gradient of the bone marrow niche to culture HSCs and induce their differentiation into the erythroid system. Cells on the low-stiffness scaffold have higher potential for erythrocyte differentiation and faster differentiation efficiency and promote erythrocyte differentiation after erythropoietin (EPO) restriction. In vivo transplantation experiments demonstrated that these cells have the ability for continuous proliferation and differentiation into mature erythrocytes. By combining mechanical cues with in vitro erythrocyte production, this method is expected to provide insights for in vitro hematopoietic design and offer a scalable cell manufacturing platform for transfusion medicine. Full article
(This article belongs to the Section Gel Applications)
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13 pages, 617 KiB  
Article
Management and Outcomes of Blunt Renal Trauma: A Retrospective Analysis from a High-Volume Urban Emergency Department
by Bruno Cirillo, Giulia Duranti, Roberto Cirocchi, Francesca Comotti, Martina Zambon, Paolo Sapienza, Matteo Matteucci, Andrea Mingoli, Sara Giovampietro and Gioia Brachini
J. Clin. Med. 2025, 14(15), 5288; https://doi.org/10.3390/jcm14155288 - 26 Jul 2025
Viewed by 311
Abstract
Background: Renal trauma accounts for approximately 3–5% of all trauma cases, predominantly affecting young males. The most common etiology is blunt trauma, particularly due to road traffic accidents, and it frequently occurs as part of polytrauma involving multiple organ systems. Management strategies are [...] Read more.
Background: Renal trauma accounts for approximately 3–5% of all trauma cases, predominantly affecting young males. The most common etiology is blunt trauma, particularly due to road traffic accidents, and it frequently occurs as part of polytrauma involving multiple organ systems. Management strategies are primarily dictated by hemodynamic stability, overall clinical condition, comorbidities, and injury severity graded according to the AAST classification. This study aimed to evaluate the effectiveness of non-operative management (NOM) in high-grade renal trauma (AAST grades III–V), beyond its established role in low-grade injuries (grades I–II). Secondary endpoints included the identification of independent prognostic factors for NOM failure and in-hospital mortality. Methods: We conducted a retrospective observational study including patients diagnosed with blunt renal trauma who presented to the Emergency Department of Policlinico Umberto I in Rome between 1 January 2013 and 30 April 2024. Collected data comprised demographics, trauma mechanism, vital signs, hemodynamic status (shock index), laboratory tests, blood gas analysis, hematuria, number of transfused RBC units in the first 24 h, AAST renal injury grade, ISS, associated injuries, treatment approach, hospital length of stay, and mortality. Statistical analyses, including multivariable logistic regression, were performed using SPSS v28.0. Results: A total of 244 patients were included. Low-grade injuries (AAST I–II) accounted for 43% (n = 105), while high-grade injuries (AAST III–V) represented 57% (n = 139). All patients with low-grade injuries were managed non-operatively. Among high-grade injuries, 124 patients (89%) were treated with NOM, including observation, angiography ± angioembolization, stenting, or nephrostomy. Only 15 patients (11%) required nephrectomy, primarily due to persistent hemodynamic instability. The overall mortality rate was 13.5% (33 patients) and was more closely associated with the overall injury burden than with renal injury severity. Multivariable analysis identified shock index and active bleeding on CT as independent predictors of NOM failure, whereas ISS and age were significant predictors of in-hospital mortality. Notably, AAST grade did not independently predict either outcome. Conclusions: In line with the current international literature, our study confirms that NOM is the treatment of choice not only for low-grade renal injuries but also for carefully selected hemodynamically stable patients with high-grade trauma. Our findings highlight the critical role of physiological parameters and overall ISS in guiding management decisions and underscore the need for individualized assessment to minimize unnecessary nephrectomies and optimize patient outcomes. Full article
(This article belongs to the Special Issue Emergency Surgery: Clinical Updates and New Perspectives)
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13 pages, 354 KiB  
Article
Clinical Impact of Viscoelastic Testing in Liver Transplantation: A Before-and-After Study of Transfusion Needs and Outcomes
by Iulian Buzincu, Mihaela Blaj, Eliza Isabela Bărbuță, Adi-Ionuț Ciumanghel, Irina Gîrleanu, Irina Ciumanghel, Ana-Maria Trofin, Vlad Nuțu, Alexandru Năstase, Ramona Cadar, Mihai Zabara, Vlad Carp, Beatrice Cobzaru, Corina Lupascu Ursulescu and Cristian Dumitru Lupașcu
J. Clin. Med. 2025, 14(14), 4882; https://doi.org/10.3390/jcm14144882 - 9 Jul 2025
Viewed by 376
Abstract
Background/Objectives: Liver transplantation (LT) is often complicated by severe bleeding and coagulopathy. Viscoelastic testing (VET) offers real-time, bedside assessment of coagulation and may improve transfusion management compared to standard tests. This study evaluates the clinical impact of VET implementation during liver transplantation [...] Read more.
Background/Objectives: Liver transplantation (LT) is often complicated by severe bleeding and coagulopathy. Viscoelastic testing (VET) offers real-time, bedside assessment of coagulation and may improve transfusion management compared to standard tests. This study evaluates the clinical impact of VET implementation during liver transplantation on bleeding, transfusion requirements, complications, and mortality in a single Eastern European tertiary transplant center. Methods: We conducted a single-center before-and-after study comparing patients undergoing LT before and after the implementation of VET. All procedures were performed by the same surgical and anesthetic team using a standardized protocol. Data were collected retrospectively for the Before VET group and prospectively for the After VET group. We compared transfusion requirements, bleeding, complications, and mortality. Results: A total of 59 patients were included, 22 in the After VET group and 37 in the Before VET group. VET implementation was associated with lower intraoperative blood loss (median 4000 mL vs. 6000 mL, p = 0.017) and reduced red blood cell (RBC) transfusion volume (670 mL vs. 1000 mL, p = 0.008). FFP (0.23 vs. 1.59 units, p = 0.007) and platelet use (0.68 vs. 1.81 units, p = 0.035) were also significantly lower in the VET group, while fibrinogen use was higher (3.00 g vs. 2.00 g, p = 0.036). No differences were observed in complication rates or mortality at 30 days and 1 year in this small before-and-after study. Conclusions: VET improved transfusion precision and individualized coagulation management during LT, leading to reduced use of blood products. These findings support the adoption of VET as a standard of care in LT protocols, as it may enhance patient safety, even though no differences in postoperative complications or mortality were observed. Full article
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14 pages, 802 KiB  
Article
Clinical Impact of Red Blood Cell Transfusion Location on Gastrointestinal Bleeding Outcomes: Emergency Department vs. Inpatient Unit
by Mehmet Toprak, Harun Yildirim, Ertan Sönmez, Murtaza Kaya, Ali Halici, Abdil Coskun and Mehmed Ulu
Healthcare 2025, 13(14), 1656; https://doi.org/10.3390/healthcare13141656 - 9 Jul 2025
Viewed by 278
Abstract
Background: Gastrointestinal (GI) bleeding is a common and potentially life-threatening condition frequently encountered in emergency departments (EDs). The optimal strategy for red blood cell suspension (RBCS) transfusion, including timing and location, remains unclear. This study aimed to evaluate the impact of transfusion location [...] Read more.
Background: Gastrointestinal (GI) bleeding is a common and potentially life-threatening condition frequently encountered in emergency departments (EDs). The optimal strategy for red blood cell suspension (RBCS) transfusion, including timing and location, remains unclear. This study aimed to evaluate the impact of transfusion location (ED vs. inpatient units) on mortality and hospital stay in patients with GI bleeding. Methods: A cross-sectional descriptive study was conducted in the ED of a tertiary care hospital. Patients admitted with GI bleeding between 1 June 2021, and 1 June 2023, who received RBCS transfusion were included. Data on demographics, laboratory parameters, transfusion details, and clinical outcomes were collected from the hospital information system. Logistic regression was used to identify mortality predictors. Results: A total of 244 patients were included. Patients transfused in the ED had a significantly shorter hospital stay compared to those transfused in inpatient units. However, mortality did not differ between the groups. Logistic regression identified age, albumin, hemoglobin, creatinine, and hospital stay as independent mortality predictors, while transfusion location was not significant. Conclusions: Early RBCS transfusion in the ED may reduce hospital stay but does not significantly impact mortality. Identifying mortality-associated factors is crucial for optimizing patient management. Further prospective studies are needed to clarify the role of transfusion location in GI bleeding outcomes. Full article
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13 pages, 296 KiB  
Article
Analysis of Massive Transfusion Protocol Utilization in Trauma Across Sociodemographic Groups
by Monique Arnold, Bharti Sharma, Matthew Conn, Kate Twelker, Navin D. Bhatia, George Agriantonis, Jasmine Dave, Juan Mestre, Zahra Shafaee and Jennifer Whittington
Medicina 2025, 61(7), 1133; https://doi.org/10.3390/medicina61071133 - 24 Jun 2025
Viewed by 464
Abstract
Background and Objectives: Blood shortages are a national crisis, creating dangerous scenarios for patients requiring the use of a massive transfusion protocol (MTP). A judicious use of blood products is critical to rescue salvageable patients while refraining from unnecessary MTP to save [...] Read more.
Background and Objectives: Blood shortages are a national crisis, creating dangerous scenarios for patients requiring the use of a massive transfusion protocol (MTP). A judicious use of blood products is critical to rescue salvageable patients while refraining from unnecessary MTP to save precious resources. This study examines effect of trauma characteristics, socioeconomic variables and markers of futility on the likelihood of activating and receiving MTP in the trauma setting. Materials and Methods: In this retrospective study, emergency department (ED) trauma activations from a database of an urban Level I trauma center were analyzed from 1 January 2017 to 30 June 2022, inclusive. In-ED mortality, RBC transfusion volumes during initial resuscitation, patient sociodemographic data, and trauma event factors were analyzed. The primary outcomes were the dichotomous outcomes of MTP activation and MTP transfusion. Univariable analyses and logistic regressions were conducted, with class balancing sensitivities applied to the multivariable regressions to adjust for imbalance in the data. p < 0.05 was considered statistically significant. Results: Among the 8670 trauma activations, there was a 0.3% in-ED mortality rate. MTP activation and MTP transfusion were associated with higher in-ED mortality rates (3.8% and 15.4%, respectively, compared to 0.2% without MTP). Younger patients, male patients, and Medicaid recipients were more likely to undergo MTP activation; Medicare patients were less likely. Penetrating trauma substantially increased the likelihood of both MTP activation (odds ratio (OR) 5.81) and transfusion (OR 3.63). The logistic regression models identified the presence of penetrating trauma, lower probability of survival, and age as the most important covariates. Models demonstrated high discriminatory value (area under the curve (AUC) of the receiver operating characteristic curve (ROC) of 0.876 for MTP activation, 0.935 for MTP transfusion) and precision (0.974 for activation, 0.994 for transfusion), with class balancing further improving model performance and precision scores. Conclusions: These results are significant as assessing the futility of MTP should be equitable, and future transfusion guidelines should consider salvageability in cases with a low probability of survival despite age and mechanism. Full article
(This article belongs to the Special Issue Trauma, Critical Care, and Acute Care Surgery)
18 pages, 4846 KiB  
Article
The Nrf2 Activator CDDO-Imidazole Suppresses Inflammation-Induced Red Blood Cell Alloimmunization
by Che-Yu Chang, Rosario Hernández-Armengol, Kausik Paul, June Young Lee, Karina Nance, Tomohiro Shibata, Peibin Yue, Christian Stehlik and David R. Gibb
Antioxidants 2025, 14(6), 678; https://doi.org/10.3390/antiox14060678 - 3 Jun 2025
Viewed by 627
Abstract
Experimental Objective: During red blood cell (RBC) transfusion, inflammation promotes the production of anti-RBC alloantibodies that can cause significant hemolytic events. Avoiding RBC antigen exposure is the only strategy to prevent RBC alloimmunization in transfusion recipients. Identifying mechanisms that inhibit alloimmunization may lead [...] Read more.
Experimental Objective: During red blood cell (RBC) transfusion, inflammation promotes the production of anti-RBC alloantibodies that can cause significant hemolytic events. Avoiding RBC antigen exposure is the only strategy to prevent RBC alloimmunization in transfusion recipients. Identifying mechanisms that inhibit alloimmunization may lead to novel prophylactic interventions. One potential regulatory mechanism is the activation of the transcription factor nuclear factor erythroid-derived 2-like 2 (Nrf2), a master regulator of antioxidant pathways. Pharmacologic Nrf2 activators induce antioxidant production and improve the sequelae of inflammatory diseases. Thus, we tested the hypothesis that a Nrf2 activator, 1-[2-cyano-3-,12-dioxooleana-1,9(11)-dien-28-oyl]-imidazole (CDDO-Im), regulates inflammation-induced RBC alloimmunization. Methods: WT and Nrf2-deficient mice were treated with inflammatory stimuli and CDDO-Im prior to transfusion with RBCs expressing the KEL antigen (KEL+ RBCs). Anti-KEL IgM and IgG were measured in the serum of transfused mice. Nrf2-activated gene expression and interferon activity were measured in mice and human macrophages pre-treated with CDDO-Im and interferon stimuli. Results: Here, we report that CDDO-Im induces Nrf2-activated gene expression and inhibits type 1 interferon activity, which promotes RBC alloimmunization in transfusion models. In mice transfused with KEL+ RBCs, pre-treatment with CDDO-Im inhibited inflammation-induced anti-KEL antibody production and increased the post-transfusion recovery of KEL+ RBCs in a Nrf2-dependent manner. CDDO-Im also inhibited RBC alloimmunization in mice with pre-existing inflammation. Conclusions: These results indicate that the activation of the Nrf2 antioxidant pathway regulates RBC alloimmunization to the KEL antigen in a pre-clinical model. If these findings translate to other models and human studies, Nrf2 activators may represent a potential prophylactic intervention to inhibit alloimmunization. Full article
(This article belongs to the Special Issue Blood Cells and Redox Homeostasis in Health and Disease, 2nd Edition)
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10 pages, 595 KiB  
Article
Tranexamic Acid Use in Total Hip Arthroplasty for Avascular Necrosis: A Single-Center Experience
by Wojciech Konarski, Michał Derczyński, Kamil Poboży, Julia Domańska-Poboża and Tomasz Poboży
J. Clin. Med. 2025, 14(10), 3399; https://doi.org/10.3390/jcm14103399 - 13 May 2025
Viewed by 426
Abstract
Background: Avascular necrosis (AVN) of the femoral head is a major indication for total hip arthroplasty (THA), often associated with significant blood loss and high transfusion rates. Tranexamic acid (TXA) has been shown to reduce perioperative bleeding, but evidence in AVN-specific populations remains [...] Read more.
Background: Avascular necrosis (AVN) of the femoral head is a major indication for total hip arthroplasty (THA), often associated with significant blood loss and high transfusion rates. Tranexamic acid (TXA) has been shown to reduce perioperative bleeding, but evidence in AVN-specific populations remains limited. Methods: This retrospective, single-center study analyzed 115 patients undergoing primary THA due to AVN between 2016 and 2023. Patients who received TXA were compared with those who did not. Baseline and perioperative data including hemoglobin (HGB), erythrocyte count (RBC), transfusion rates, and PRBC unit use were collected. Results: Baseline characteristics were comparable between groups. TXA significantly reduced transfusion incidence (7.9% vs. 36.5%, p < 0.0001) and total PRBC unit use (0.1 ± 0.3 vs. 0.8 ± 1.1, p < 0.0001). The mean HGB drop was smaller in the TXA group (2.1 ± 1.2 vs. 3.2 ± 2.0 g/dL, p = 0.001), as well as the RBC drop (0.8 ± 0.4 vs. 1.3 ± 1.4 million/μL, p = 0.02). Conclusions: TXA effectively reduces blood loss and transfusion needs in AVN-related THA, supporting its routine perioperative use in this patient population. Full article
(This article belongs to the Section Orthopedics)
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10 pages, 222 KiB  
Article
Prevalence and Specificity of Red Blood Cell Alloimmunization: Insights from Transfusion-Dependent Populations in Serbia
by Radovan Dinić, Nevenka Bujandrić and Jasmina Grujić
Thalass. Rep. 2025, 15(2), 5; https://doi.org/10.3390/thalassrep15020005 - 7 May 2025
Viewed by 951
Abstract
Background/Objectives: Red blood cell (RBC) alloimmunization is a significant challenge in transfusion medicine, particularly among transfusion-dependent patients, such as those with thalassemia. It arises from the production of antibodies against non-self RBC antigens and can lead to complications like hemolytic transfusion reactions. This [...] Read more.
Background/Objectives: Red blood cell (RBC) alloimmunization is a significant challenge in transfusion medicine, particularly among transfusion-dependent patients, such as those with thalassemia. It arises from the production of antibodies against non-self RBC antigens and can lead to complications like hemolytic transfusion reactions. This study aimed to evaluate the prevalence, specificity, and clinical implications of RBC alloimmunization at the University Clinical Center of Serbia (UCCS), emphasizing transfusion-dependent populations. Methods: This retrospective study analyzed 27,530 transfusion records at UCCS between January 2023 and January 2024. Pre-transfusion testing included ABO and RhD typing, irregular antibody screening, and crossmatching. Data from 630 patients with positive antibody screening were reviewed. Alloantibody specificity was determined using indirect antiglobulin tests and advanced phenotyping methods. Results: Among 27,530 patients, 630 (2.29%) tested positive for irregular antibodies, predominantly males (57.14%) with a mean age of 49.6 years. Alloantibodies were detected in 70.47% of cases, most commonly targeting Rh (53.35%) and Kell (17.15%) systems. Anti-E (27.93%) and anti-D (18.02%) were the most frequent antibodies. Multiple alloantibodies were identified in 18.41% of patients, posing challenges for blood compatibility. In a total of 495 patients with thalassemia, antibodies were found in 9.69%. Alloimmunization was significantly associated with higher numbers of transfusions and pregnancies (p < 0.05). Conclusions: Our findings indicate that alloimmunization is predominantly associated with Rh and Kell antigens, suggesting that implementing targeted antigen matching may reduce the frequency of alloimmunization. While our study does not directly assess the impact of genotypic matching, the prior literature supports its role in enhancing transfusion safety, particularly for high-risk populations like thalassemia patients. Full article
24 pages, 2813 KiB  
Article
Real-World Evidence of the Disease Burden and Economic Impact of Paroxysmal Nocturnal Hemoglobinuria in Italy
by Roberta Bini, Lorena D’Anna, Diletta Valsecchi, Stefania Mazzoni, Valentina Perrone and Luca Degli Esposti
J. Clin. Med. 2025, 14(9), 2889; https://doi.org/10.3390/jcm14092889 - 22 Apr 2025
Viewed by 940
Abstract
Background/Objectives: This analysis was conducted in Italy to estimate the epidemiology of paroxysmal nocturnal hemoglobinuria (PNH) and to describe the features and economic burden of PHN in the adult population considering the role of anti-complement therapy with C5/3-inhibitors (C5/3i). Methods: Administrative [...] Read more.
Background/Objectives: This analysis was conducted in Italy to estimate the epidemiology of paroxysmal nocturnal hemoglobinuria (PNH) and to describe the features and economic burden of PHN in the adult population considering the role of anti-complement therapy with C5/3-inhibitors (C5/3i). Methods: Administrative databases of healthcare entities covering approximately 12 million citizens were used to estimate the prevalence and incidence of PNH. Demographics, clinical characteristics and healthcare costs were analyzed among adults with PHN stratified by the presence/absence of C5/3i therapy. Results: The prevalence in Dec-2021 of PNH in adults was 17.6/1,000,000 people, and the incidence rate in the period 2011–2022 was 1.5/1,000,000/year. In 142 patients with at least 12 months of data available before and after inclusion (mean age: 50.7 years; 45.8% males), 27% received C5/3i therapy. The main baseline comorbidities were aplastic anemia and other bone marrow failure syndromes, found in 10.6% of patients and more common in C5/3i-treated than untreated patients (18.4% vs. 7.7%). Cost analysis showed that the average cost per patient per year (PPPY) was EUR 41,084, mainly driven by drug expenses (87% of total costs), especially anti-complement therapy (80%). RBC transfusions were the most impactive item among the hospitalization costs (EUR 1982 of EUR 4284 PPPY). The C5/3i-treated cohort was associated with higher total costs (EUR 133,472 vs. EUR 8089, p < 0.001), mainly due to drug expenses (EUR 127,180 vs. EUR 3217, p < 0.001). Conclusions: This real-world analysis confirmed a rising PNH prevalence in Italy, aligning with global data. Despite available therapies, many patients face a high disease burden, suggesting potential benefits from novel treatments targeting upstream complement components. Full article
(This article belongs to the Section Epidemiology & Public Health)
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11 pages, 778 KiB  
Article
Perioperative Red Blood Cell Transfusion and Long-Term Mortality in Coronary Artery Bypass Grafting: On-Pump and Off-Pump Analysis
by Seung Hyung Lee, Ji Eon Kim, Jun Ho Lee, Jae Seung Jung, Ho Sung Son and Hee-Jung Kim
J. Clin. Med. 2025, 14(8), 2662; https://doi.org/10.3390/jcm14082662 - 13 Apr 2025
Cited by 2 | Viewed by 526
Abstract
Background/Objectives: The impact of different coronary artery bypass grafting (CABG) strategies, particularly on-pump versus off-pump techniques, on red blood cell (RBC) transfusions and their associated outcomes has not been fully investigated. This study aims to evaluate the association between RBC transfusion and [...] Read more.
Background/Objectives: The impact of different coronary artery bypass grafting (CABG) strategies, particularly on-pump versus off-pump techniques, on red blood cell (RBC) transfusions and their associated outcomes has not been fully investigated. This study aims to evaluate the association between RBC transfusion and survival in CABG patients, focusing on-pump strategy. Methods: Data from CABG patients were retrieved from the National Health Insurance Service database (2003 to 2019). Perioperative RBC transfusions were classified into three groups: no transfusion, RBC 1, and RBC ≥ 2 units. The primary endpoint was all-cause mortality rate. Subgroup analysis assessed the impact of RBC transfusion on mortality across the conventional on-pump (CCAB) and off-pump (OPCAB) groups. Results: Among the 6150 participants who underwent CABG, 2028 underwent CCAB and 4122 underwent OPCAB. The mean age was 66.2 ± 9.7 years, with a mean follow-up of 2.9 (2.53–3.35) years. Multivariable analysis showed a significant association between transfusion of ≥2 RBC units and increased mortality risk (HR 2.34 [1.65–3.32], p < 0.001). Subgroup analysis showed a similar trend in both CCAB and OPCAB groups (p for interaction = 0.2). Transfusion of ≥2 units significantly increased mortality in OPCAB (HR 2.28 [1.55–3.37], p < 0.001) but not in CCAB (HR 2.96 [0.97–9.06], p = 0.057). OPCAB and surgery at large volume center was associated with a reduced risk of RBC transfusion (p < 0.01). Conclusions: Increased RBC transfusion is associated with higher long-term mortality in patients undergoing CABG. Based on a large cohort predominantly consisting of OPCAB patients, OPCAB is associated with decreased RBC transfusion requirements. Full article
(This article belongs to the Special Issue Clinical Advances in Cardiac Anesthesia and Critical Care)
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10 pages, 457 KiB  
Article
Integrating RHD Genotyping for More Accurate Rh(D) Antigen Phenotyping: A Retrospective Study
by Mohammad Barouqa and Nestor Dela Cruz
Medicina 2025, 61(4), 670; https://doi.org/10.3390/medicina61040670 - 5 Apr 2025
Viewed by 671
Abstract
Background and Objectives: The Rh blood group system is highly polymorphic, and accurate classification of Rh(D) variants is critical in transfusion medicine to prevent alloimmunization and optimize blood utilization. Despite the advances in conventional serologic testing, weak and partial Rh(D) phenotypes still remain [...] Read more.
Background and Objectives: The Rh blood group system is highly polymorphic, and accurate classification of Rh(D) variants is critical in transfusion medicine to prevent alloimmunization and optimize blood utilization. Despite the advances in conventional serologic testing, weak and partial Rh(D) phenotypes still remain challenges in Transfusion Medicine practice. The objective is to implement and assess the impact of RHD genotyping in classifying Rh(D) antigen status. Materials and Methods: We conducted a retrospective study at the University of South Alabama Medical Center and Children and Women’s Hospital between 1 January 2023 and 31 December 2024 to assess the impact of RHD genotyping in cases with discrepant Rh(D) typing, Rh(D)-positive patients with anti-Rh(D) antibodies, and neonates with positive weak Rh(D) tests. ABO and Rh(D) antigen typing was performed on 12,994 patients, including 3767 newly tested individuals. Weak Rh(D) testing was performed on newly tested individuals using automated microplate direct agglutination, followed by molecular genotyping. Results: Among the 25 patients with weak or discrepant Rh(D) phenotypes, weak Rh(D) variants were observed in 52% of cases, with Weak Type 2 being the most common, particularly in pediatric (age < 18 years old) patients. Partial Rh(D) phenotypes were identified in 40% of cases, predominantly among Black individuals. Three patients were reclassified as Rh(D)-positive based on genotyping and received 615 Rh(D)-positive RBC units without evidence of alloimmunization, while four patients were confirmed at risk of alloimmunization and remained classified as Rh(D)-negative. Fisher’s exact test demonstrated a significant association between ethnicity and Rh(D) classification (p < 0.01), and the McNemar exact test confirmed a significant reclassification of cases from Rh(D)-negative to Rh(D)-positive (p < 0.01). Conclusions: RHD genotyping enhances the accuracy of Rh(D) antigen classification, mitigating alloimmunization risks and the unnecessary use of Rh Immunoglobulin and optimizing blood product utilization. The reclassification of patients to Rh(D)-positive alleviates pressure on Rh(D)-negative blood supplies, particularly during critical shortages. These findings underscore the necessity of integrating molecular RHD testing into routine transfusion medicine practices to improve patient safety and resource management. Full article
(This article belongs to the Section Hematology and Immunology)
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12 pages, 1874 KiB  
Systematic Review
Mortality in Critically Ill Patients with Liberal Versus Restrictive Transfusion Thresholds: A Systematic Review and Meta-Analysis of Randomized Controlled Trials with Trial Sequential Analysis
by Daniel Arturo Jiménez Franco, Camilo Andrés Pérez Velásquez and David Rene Rodríguez Lima
J. Clin. Med. 2025, 14(6), 2049; https://doi.org/10.3390/jcm14062049 - 18 Mar 2025
Viewed by 1540
Abstract
Background/Objectives: Anemia is common in critically ill patients, yet red blood cell (RBC) transfusion without active bleeding does not consistently improve outcomes and carries risks such as pulmonary injury, fluid overload, and increased costs. Optimal transfusion thresholds remain debated, with some guidelines [...] Read more.
Background/Objectives: Anemia is common in critically ill patients, yet red blood cell (RBC) transfusion without active bleeding does not consistently improve outcomes and carries risks such as pulmonary injury, fluid overload, and increased costs. Optimal transfusion thresholds remain debated, with some guidelines recommending a restrictive target of 7 g/dL instead of a more liberal target of 9 g/dL. Methods: We conducted a systematic review and meta-analysis following PRISMA guidelines, searching PubMed, EMBASE, and LILACS from January 1995 to October 2024. Thirteen randomized controlled trials involving 13,705 critically ill adults were included, with 6855 assigned to liberal and 6850 to restrictive transfusion strategies. The risk of bias was assessed using the Cochrane Risk of Bias Tool 2, and the pooled effect sizes were estimated with a random-effects model. We registered the protocol in PROSPERO International Prospective Register of Systematic Reviews (CDR42024589225). Results: No statistically significant difference was observed in 30-day mortality between restrictive and liberal strategies (odds ratio [OR] 1.02; 95% confidence interval [CI], 0.83–1.25; I2 = 49%). Similarly, no significant differences emerged for the 90-day or 180-day mortality, hospital or intensive care unit (ICU) length of stay, dialysis requirement, or incidence of acute respiratory distress syndrome (ARDS). However, patients in the restrictive group received significantly fewer RBC units. The trial sequential analysis (TSA) indicated that the evidence accrued was insufficient to definitively confirm or exclude an effect on the 30-day mortality, as the required sample size was not reached. Conclusions: In conclusion, while our meta-analysis found no statistically significant difference in the short-term mortality between restrictive and liberal transfusion strategies, larger trials are needed to fully determine whether any clinically meaningful difference exists in critically ill populations. Full article
(This article belongs to the Special Issue Clinical Advances in Critical Care Medicine)
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9 pages, 450 KiB  
Article
Effect of Homozygous Sickle Cell Anemia on Perinatal Outcomes: A Retrospective Cohort Study
by Ahmet Zeki Nessar, Fikriye Işıl Adıgüzel, Sefanur Gamze Karaca, Yusuf Dal, Zeynep Küçükolcay Coşkun and Ayhan Coşkun
J. Clin. Med. 2025, 14(6), 1967; https://doi.org/10.3390/jcm14061967 - 14 Mar 2025
Viewed by 711
Abstract
Backgrounds: Sickle cell anemia (SCA) is a multisystemic disorder that causes hemolytic anemia and impaired tissue perfusion due to sickling of red blood cells. Although there is a belief that adverse perinatal outcomes are frequent in pregnant women with SCA, this association [...] Read more.
Backgrounds: Sickle cell anemia (SCA) is a multisystemic disorder that causes hemolytic anemia and impaired tissue perfusion due to sickling of red blood cells. Although there is a belief that adverse perinatal outcomes are frequent in pregnant women with SCA, this association has not been clearly established. The aim of this study was to compare the perinatal outcomes of women with homozygous mutated SCA who gave birth with those without the mutation. Methods: The study included 26 SCA patients with homozygous mutation and 108 pregnant women without mutation who gave birth in our center. Demographic and obstetric data, laboratory findings, and fetal findings of both groups were compared. Results: Statistically significant differences were found between the groups in terms of maternal age, body mass index (BMI), gravida, and parity (p ≤ 0.001, p = 0.035, p ≤ 0.001, p ≤ 0.001, respectively). Mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), red blood cell count (RBC), hemoglobin (Hb), and hematocrit (Hct) values were significantly lower in the SCA group. We also observed that more blood transfusions were performed during pregnancy and the postpartum period in the SCA group. Low birth weight, more neonatal intensive care unit admissions, and a higher cesarean section rate were present in the SCA group. During pregnancy, women with SCA were most frequently admitted to the hospital for acute painful crises. Preeclampsia was not more common in the SCA group. Conclusions: SCA carries serious risks for the mother and fetus during pregnancy. Therefore, the relationship between the disease and pregnancy requires more detailed research. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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13 pages, 670 KiB  
Article
Transfusion Thresholds and Risk Factors of Acute Kidney Injury in Gastrointestinal Oncology Surgery: Insights from a Retrospective Study
by Shuai Ma, Qi He, Chengcan Yang, Zhiyuan Zhou, Yining He, Chaoran Yu, Danhua Yao, Lei Zheng, Yuhua Huang and Yousheng Li
Healthcare 2025, 13(5), 525; https://doi.org/10.3390/healthcare13050525 - 28 Feb 2025
Viewed by 1050
Abstract
Objectives: To identify transfusion thresholds and risk factors for acute kidney injury (AKI) in gastrointestinal oncology surgery, enhancing early intervention and improving postoperative outcomes. Methods: From 2018 to 2022, 765 patients with gastric or colorectal cancer who underwent major gastrointestinal surgery [...] Read more.
Objectives: To identify transfusion thresholds and risk factors for acute kidney injury (AKI) in gastrointestinal oncology surgery, enhancing early intervention and improving postoperative outcomes. Methods: From 2018 to 2022, 765 patients with gastric or colorectal cancer who underwent major gastrointestinal surgery were retrospectively enrolled. The primary outcome was AKI development within 7 days postoperatively. Clinicopathological characteristics and short-term outcomes were recorded and compared. Results: Of all enrolled patients, 39 (5.1%) developed AKI. Patients with AKI were predominantly older and had more preoperative comorbidities, lower levels of preoperative hemoglobin and serum albumin, but higher levels of blood urea nitrogen and serum creatinine (SCr). Patients developing AKI experienced higher rates of in-hospital complications (overall: 48.3% vs. 14.2%, p < 0.001), prolonged hospital stays (25.4 ± 22.5 days vs. 12.3 ± 7.9 days, p < 0.001), increased intensive care unit (ICU) admissions (53.8% vs. 22.5%, p < 0.001), and higher rates of 30-day re-admission (13.9% vs. 2.4%, p = 0.003). Significant AKI risk factors included age (per 10 years, OR: 1.567, 95% CI: 1.103–2.423, p = 0.043), preoperative SCr (per 10 μmol/L, OR: 1.173, 95% CI: 1.044–1.319, p = 0.007), intraoperative RBC transfusion (per 1000 mL, OR: 1.992, 95% CI: 1.311–3.027, p = 0.001 with a significant surge in AKI risk at transfusions exceeding 1500 mL), patient-controlled analgesia (protective, OR:0.338, 95% CI: 0.163–0.928, p = 0.033), and diuretic use (OR: 5.495, 95% CI: 1.720–17.557, p = 0.004). Conclusions: Early intervention is essential for patients with preoperative low perfusion or anemia, with particular emphasis on moderating interventions to avoid fluid overload while carefully avoiding nephrotoxic medications, thereby improving postoperative outcomes. Full article
(This article belongs to the Section Perioperative Care)
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18 pages, 268 KiB  
Article
The Cost of Downstream Adverse Outcomes Associated with Allogeneic Blood Transfusion: A Retrospective Observational Cohort Study
by Michelle Roets, David John Sturgess, Kerstin Hildegard Wyssusek, Sung Min Lee, Melinda Margaret Dean and Andre van Zundert
Healthcare 2025, 13(5), 503; https://doi.org/10.3390/healthcare13050503 - 26 Feb 2025
Viewed by 692
Abstract
Background: ‘Downstream’ adverse outcomes associated with transfusion-related immune modulation (TRIM) occur postoperatively. The potential associations between these outcomes (and costs) and perioperative transfusion are often not considered by clinicians and therefore underestimated. When considering TRIM, many advantages of intraoperative cell salvage (ICS) were [...] Read more.
Background: ‘Downstream’ adverse outcomes associated with transfusion-related immune modulation (TRIM) occur postoperatively. The potential associations between these outcomes (and costs) and perioperative transfusion are often not considered by clinicians and therefore underestimated. When considering TRIM, many advantages of intraoperative cell salvage (ICS) were previously confirmed. Methods: The main aim of this retrospective observational study was to evaluate the cost implications associated with perioperative adverse outcomes following allogeneic blood transfusion (ABT). Secondly, further analysis considered downstream costs following ICS. This manuscript does not aim to provide evidence of improved outcomes following ICS compared to ABT. These outcomes were previously demonstrated. Instead, it is important to consider downstream cost implications if patients receive ABT, despite previously proven benefits related to ICS. Surgical patients (n = 2129) receiving blood transfusion at the Royal Brisbane and Women’s Hospital (Queensland, Australia) (2016–2018) were included: receiving ICS only (n = 115), allogeneic red blood cells (RBCs) only (n = 1944), or RBCs and ICS (n = 70). Data retrieved from eight hospital databases were exported, and a novel Structured Query Language (SQL) database was developed to link data points. Adverse outcomes previously associated with TRIM were assessed using International Classification of Diseases-10 (ICD-10) coded data. Generalised linear models were used to model costs and adjust for confounding factors. Results: Most adverse outcomes (≥3) occurred following RBCs and ICS (37.1%), followed by RBCs (23.7%) and ICS (16.5%). As potentially important determinants of overall expenditure, the lowest marginal mean intensive care stay (days, cost) was after ICS (2.1 days, AUD 10,027), followed by RBCs and ICS (3.8 days, AUD 18,089), and then RBCs (5.5 days, AUD 26,071). When considering blood products (other than packed red blood cells), the average cost per patient was lowest for ICS (AUD 48), followed by RBCs (AUD 533) and RBCs and ICS (AUD 819). Conclusions: We confirmed that the cost associated with allogeneic blood transfusion was significant; patients receiving packed red blood cells (pRBCs) experienced more adverse outcomes and higher hospital costs than those receiving ICS. These results are limited to retrospective data and require further prospective validation. Full article
(This article belongs to the Section Critical Care)
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