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Red blood cell (RBC) alloimmunization is more common in patients with sickle cell disease (SCD) than in any other studied patient population. The high prevalence of RBC alloimmunization is multi-factorial, likely involving the chronic hemolysis and inflammatory status of SCD itself, the transfusion burden of patients, and the RH genetic diversity of patients and blood donors, among other reasons. Antibody evanescence, or the decrease of RBC alloantibodies below levels detectable by blood bank testing, occurs frequently with fewer than 30% of alloantibodies estimated to be detected by current screening practices. Evanescence increases the likelihood that a patient with SCD will have a delayed hemolytic transfusion reaction upon future RBC exposure, with previously undetected alloantibodies coming roaring back in an anamnestic manner after exposure to the cognate RBC antigen. A subset of patients having delayed hemolytic transfusion reactions go on to experience hyperhemolysis; some but not all cases of hyperhemolysis are associated with previously evanescent RBC alloantibodies. There is an increasing appreciation of the association between RBC alloantibodies and RBC autoantibodies, as well as involvement of the alternative complement pathway in some instances of hyperhemolysis. A case report in this manuscript describes a highly alloimmunized patient with SCD who experiences a delayed hemolytic transfusion reaction with bystander hemolysis due to a previously evanescent, complement binding anti-M RBC alloantibody. Additional studies, including those involving multiple centers and countries, are needed to further understand RBC alloimmunization in patients with SCD and to develop strategies to prevent or mitigate potentially life-threatening hemolytic transfusion reactions., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Emerging data in animal models and humans suggest that pathogen-associated and damage-associated molecular patterns variably impact RBC alloantibody formation. In this study, we tested the hypothesis that vaccinations may enhance immune responses to transfused RBCs. The Pneumovax23 vaccine decreased the magnitude of anti-KEL alloimmunization in a murine model, whereas the hepB vaccine did not impact the response; RBC transfusion did not alter immune responses to either vaccine. These data highlight the complexities of the intersection of innate and adaptive immunity and suggest that future studies investigating the pathways through which inflammation impacts alloimmunization are warranted., (© 2017 International Society of Blood Transfusion.)

We hypothesized that diagnoses may be associated with alloantibody 'responder' status and examined associations between disease states and alloimmunization. Patients with ≥1 alloantibody and non-alloimmunized controls were analysed. Pearson's coefficients were calculated to determine associations between alloimmunization and diseases; significant correlations were selected to construct a network. Inflammatory disorders and diseases requiring chronic transfusion support were associated with responder status. Mitigation steps may be considered in patients with these disorders., (Published 2017. This article is a U.S. Government work and is in the public domain in the USA.)

Background and Objectives: Fetuses affected by maternal RBC alloantibodies may have prolonged anaemia after birth, leading one to question whether maternal alloantibody transfer may occur outside the placenta. In response to a recent publication describing breast milk transfer of clinically significant amounts of maternal antiplatelet IgA antibodies from mother to nursing infant, we hypothesized that maternal RBC alloantibodies may also be capable of being transferred in breast milk., Materials and Methods: The presence and clinical significance of breast milk alloantibody transfer were tested through a series of pregnancy, fostering and transfusion experiments, using a murine model in which transgenic RBCs express the human KEL glycoprotein., Results: Maternal anti-KEL immunoglobulins, induced through transfusion or pregnancy, were detected in the aqueous phase of breast milk. Further, efficient transfer of maternal anti-KEL IgG and IgA to nursing pups was observed in fostering experiments. The breast milk-acquired alloantibodies were clinically significant in wild-type pups in a transfusion setting, binding to 'incompatible' KEL RBCs and leading to premature clearance from the circulation. Although breast milk-acquired alloantibodies also bound to the RBCs of transgenic KEL-positive fostered pups, no anaemia resulted., Conclusions: Taking these murine data in combination with recently published human data of maternal antiplatelet IgA antibodies in breast milk leading to sequelae in some infants, it is theoretically possible that maternal anti-RBC IgA alloantibodies may also be transferred in human breast milk and may lead to sequelae in some infants under some circumstances., (© 2016 International Society of Blood Transfusion.)

Mice provide tractable animal models for studying the pathophysiology of various human disorders. This review discusses the use of mouse models for understanding red-blood-cell (RBC) clearance. These models provide important insights into the pathophysiology of various clinically relevant entities, such as autoimmune haemolytic anaemia, haemolytic transfusion reactions, other complications of RBC transfusions and immunomodulation by Rh immune globulin therapy. Mouse models of both antibody- and non-antibody-mediated RBC clearance are reviewed. Approaches for exploring unanswered questions in transfusion medicine using these models are also discussed.

Millions of RBC units are transfused throughout the world annually. Even though each RBC unit contains multiple foreign donor antigens, only a minority of transfusion recipients will develop detectable RBC alloantibodies. Some factors that influence humoral immune responsiveness to transfused RBCs are obvious, including the necessity of being exposed to a foreign antigen that the immune system can process and present. Mathematically, however, every RBC transfusion meets those criteria. Thus, it remains unclear why some patients form alloantibodies (‘responders’), while others may be transfused hundreds of times without becoming alloimmunised (‘non‐responders’). Studies in humans have found an association with CD4+ T‐cell markers and responsiveness to transfused RBCs, and have also identified acute or chronic inflammatory disease states as risk factors for alloantibody development. Studies in animal models, which allow single variables to be isolated, have led to an understanding of the critical role played by dendritic cells in transfusion‐associated RBC alloimmunisation. Murine studies have further established that non‐responsiveness to transfused RBCs equates to antigen‐specific tolerance in some settings: alloantibodies develop to RBCs expressing some blood group antigens only when the initial RBC exposure occurs in close association with a danger signal. Additional studies are needed in humans and in animal models to further understand the complex variables that determine when and how a humoral immune response may be initiated against transfused RBC antigens, such that strategies for preventing alloimmunisation and its harmful effects in transfusion and pregnancy scenarios can be developed. [ABSTRACT FROM AUTHOR]

Background and Objectives One of the challenges surrounding blood component administration is the determination of an appropriate rate of infusion. There are very few evidence-based guidelines available to guide healthcare providers looking for a 'standard' infusion rate for red blood cells ( RBCs), plasma or platelets ( PLTs). Our objective was to determine the extent to which blood component infusion rates were associated with changes in transfusion recipient vital signs. Materials and Methods We retrospectively examined records of 3496 component infusions ( RBCs, n = 2359; PLTs, n = 478; plasma, n = 659) over a 1-year period at a 362-bed multispecialty hospital. The following data were collected for each transfusion: blood product volume and infusion time, recipient pre- and post-transfusion temperature, blood pressure and pulse rate, and hospital ward where transfusion occurred. Results Plasma (median 10·4 ml/min) was infused faster than PLTs (median 7·2 ml/min, P < 0·0001) or RBCs (median 2·3 ml/min, P < 0·0001). For all blood components, infusion rates varied based on the hospital unit performing the infusion. No association was found between relatively fast RBC, plasma or PLT infusion rates (>20 ml/min) and clinically significant reported changes in vital signs. Conclusions There does not appear to be a strong correlation between infusion rate and significant changes in recipient temperature, blood pressure or pulse rate. Based on these data, a reasonable rate for routine transfusion is 2-3 ml/min for RBCs and 7-10 ml/min for plasma and PLTs. Faster infusion rates (>20 ml/min) likely can be applied with close patient monitoring if there is a more urgent need for transfusion. [ABSTRACT FROM AUTHOR]