Assessing the function of transfused blood components within the dynamic environment of the vascular system remains challenging, as conventional assays are largely static and poorly represent the dynamic mechanical and biochemical interactions between blood cells and the vessel wall. Microfluidic approaches, which study blood flow within small-scale channels, provide an opportunity to bridge this gap by introducing physiologically relevant flow and shear rates into experimental models. This review synthesises the current literature describing the application of microfluidic technologies to the assessment of transfused blood components, with particular emphasis on platelet concentrates, red cell concentrates and plasma-derived products. Across existing studies, microfluidic models have demonstrated differences in component function related to storage conditions, manufacturing methods and emerging transfusion products that are not always detected using conventional bulk assays. These approaches have provided new insights into platelet haemostasis at defined shear rates, red cell deformability and gas exchange, and plasma-mediated coagulation in trauma and critical illness. However, substantial diversity in device design, experimental conditions and analytical endpoints limits direct comparison between studies and constrains translation into routine practice. The development of more standardised platforms, alongside integration with endothelialised and organ-on-a-chip models, may help to overcome these challenges. Overall, microfluidics represents a promising tool for improving functional assessment of blood components and supporting future advances in transfusion medicine research and personalised transfusion strategies.

Phototherapy remains the first-line treatment of haemolytic disease of the newborn (HDN), a potentially life-threatening condition caused by maternal alloimmunisation. Intravenous immunoglobulin (IVIG) has been proposed as an adjunct to reduce the need for exchange transfusion (ET), a procedure associated with significant risks. This meta-analysis aims to evaluate the safety and efficacy of IVIG combined with phototherapy versus phototherapy alone in neonates with HDN. A comprehensive search of MEDLINE, EMBASE, CINAHL and the Cochrane Library was conducted up to 24 April 2025. Eligible studies included randomised controlled trials and observational cohorts evaluating IVIG in HDN. Data were pooled using random-effects models. This study was prospectively registered in Prospective Register of Systematic Reviews (CRD420251025766). Nineteen studies involving 3673 neonates met the inclusion criteria. IVIG reduced the need for ET (odd ratio [OR] = 0.34; confidence interval [CI]: 0.2-0.8; I[2] = 88%) when used as an adjunct to phototherapy compared to phototherapy alone. Subgroup analysis suggested that the reduction in ET was more consistent in Rh-mediated HDN (OR = 0.2; CI: 0.1-0.8; I[2] = 81%) than in ABO-mediated HDN (OR = 0.76; CI: 0.1-4.1; I[2] = 89%). There were no differences in the length of hospital stay (mean difference [MD] = -0.1 days; CI: -0.8 to 0.6; I[2] = 98%), duration of phototherapy (MD = -5.1 h; CI: -15.7 to 5.4; I[2] = 98%) or incidence of adverse events (OR = 1.32; CI: 0.2-10.5; I[2] = 91%) between groups. Despite reducing ET requirements, adjunctive IVIG with phototherapy may not provide additional clinical benefits compared with phototherapy alone. Further high-quality trials are needed to clarify optimal timing, dosing and patient selection.

Sickle cell disease (SCD) is one of the most common inherited haemoglobin disorders worldwide and is associated with substantial morbidity, premature mortality and lifelong healthcare utilisation. Red blood cell (RBC) transfusion remains a cornerstone of SCD management and is indispensable for the treatment and prevention of life-threatening complications, including acute chest syndrome, ischaemic stroke, severe anaemia and perioperative complications. Despite its undeniable therapeutic benefits, repeated transfusions are accompanied by important adverse consequences, including alloimmunisation, iron overload, delayed haemolytic transfusion reactions and transfusion-transmitted infections. Beyond haemoglobin S dilution, transfusion therapy interacts with the chronic inflammatory and immune-activated milieu characteristic of SCD. Persistent haemolysis, endothelial dysfunction, nitric oxide depletion, leukocyte and platelet activation collectively influence both disease severity and transfusion-related immune responses, thereby contributing to alloantibody formation and other immunological complications. This review provides a comprehensive overview of the clinical indications, transfusion strategies, immunological mechanisms and transfusion-related complications in patients with SCD. Particular emphasis is placed on the cellular and molecular mechanisms underlying alloimmunisation, including the roles of antigen-presenting cells, CD4[+] T lymphocytes, B cells and regulatory T cells. Contemporary approaches to minimising transfusion-related complications-including extended antigen matching, molecular RBC genotyping, routine alloantibody screening, iron chelation therapy and emerging immunomodulatory strategies-are critically discussed. In addition, the review highlights regional challenges and evolving transfusion practices in Saudi Arabia, including newborn screening programmes, comprehensive care initiatives, donor-recipient antigen mismatch and implementation of national transfusion strategies. By integrating current evidence from clinical medicine, immunology and transfusion science, this review provides clinicians with an updated framework for optimising transfusion therapy while minimising preventable complications and improving long-term outcomes in patients with SCD.

SARS-CoV-2 infection is associated with a broad spectrum of red blood cell (RBC)-directed immune responses, ranging from isolated direct antiglobulin test (DAT) positivity to autoimmune hemolytic anemia (AIHA) and transfusion-related diagnostic challenges. This narrative review integrates current evidence on the mechanisms underlying these abnormalities, their clinical manifestations, and their implications for transfusion medicine. Molecular mimicry, bystander B-cell activation, complement dysregulation, oxidative membrane injury, and structural erythrocyte remodeling appear to represent interconnected mechanisms promoting immune recognition and altered function of RBCs. DAT positivity is frequently observed in hospitalized patients with COVID-19, often in the absence of clinically significant hemolysis, emphasizing that a positive DAT should not be considered synonymous with AIHA. Autoantibodies, complement deposition, and occasional alloimmune responses may complicate antibody identification, compatibility testing, and selection of appropriate blood components. Available evidence remains limited by heterogeneous study designs and the predominance of observational studies and case reports. Recognition of RBC-directed immune responses as part of COVID-19-associated immune dysregulation may improve interpretation of immunohematological findings, facilitate appropriate transfusion support, and help distinguish clinically significant immune hemolysis from isolated serological abnormalities.

The Rh-null phenotype is the rarest known red blood cell phenotype and is characterised by the complete absence of Rh antigens. During pregnancy, women with the Rh-null phenotype face unique challenges related to alloimmunisation against high-prevalence Rh antigens, haemolytic disease of the fetus and newborn, and the extremely limited availability of compatible blood for maternal or neonatal transfusion. We conducted a structured narrative review to identify published reports describing pregnancy-related or neonatal outcomes associated with the Rh-null phenotype, focusing on maternal antibody status, transfusion management, fetal monitoring, intrauterine intervention and maternal and neonatal outcomes. Eight reports published between 1983 and 2024 were identified. Anti-Rh29 was explicitly reported in three cases, whereas additional reports described panreactive antibody patterns consistent with antibodies directed against high-prevalence Rh antigens. Clinical outcomes ranged from mild neonatal haemolysis to severe fetal or neonatal disease. One pregnancy required intrauterine transfusion for severe fetal anaemia, and another neonate underwent repeated exchange transfusions because of severe haemolytic disease. Antenatal autologous blood donation was reported in one case as a proactive transfusion strategy. Pregnancy in women with the Rh-null phenotype requires advanced immunohaematologic investigation and specialised transfusion support. Early identification of Rh-null status, comprehensive antibody evaluation, coordinated maternal-fetal surveillance and proactive transfusion planning are central to management, ideally through multidisciplinary collaboration and access to rare donor resources.