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Blood transfusion is very safe; occasionally, however, the recipient has an adverse reaction to the donor blood. This review summarizes the types of transfusion reactions and how to diagnose and manage them.

Background Deceased organ donations are rare in Japan, with most kidney transplants performed from a limited number of living donors. Researchers have thus developed highly successful ABO-incompatible transplantation procedures, emphasizing preoperative desensitization and postoperative immunosuppression. A recent open-label, single-arm, multicenter clinical study prospectively examined the efficacy and safety of rituximab/mycophenolate mofetil desensitization in ABO-incompatible kidney transplantation without splenectomy. Methods Mycophenolate mofetil and low dose steroid were started 28 days pretransplant, followed by two doses of rituximab 375 mg/m 2 at day −14 and day −1, and postoperative immunosuppression with tacrolimus or ciclosporin and basiliximab. The primary endpoint was the non-occurrence rate of acute antibody-mediated rejection. Patient survival and graft survival were monitored for 1 year posttransplant. Results Eighteen patients received rituximab and underwent ABO-incompatible kidney transplantation. CD19-positive peripheral B cell count decreased rapidly after the first rituximab infusion and recovered gradually after week 36. The desensitization protocol was tolerable, and most rituximab-related infusion reactions were mild. No anti-A/B antibody-mediated rejection occurred with this series. One patient developed anti-HLA antibody-mediated rejection (Banff 07 type II) on day 2, which was successfully managed. Patient and graft survival were both 100 % after 1 year. Conclusion Our desensitization protocol was confirmed to be clinically effective and with acceptable toxicities for ABO-I-KTx (University Hospital Medical Information Network Registration Number: UMIN000006635).

Background ABO incompatibility is the most common blood group incompatibility in newborn babies, haemolytic disease develops in very few cases and is much milder than Rh incompatibility. In our study, we aimed to retrospectively examine the changes in platelet parameters, in addition to the expected decrease in the erythrocyte count, in immunized ABO incompatible patients, by comparing them with those in the control group. Methods The demographic data and laboratory results of patients born in our hospital between November 1, 1997, and December 31, 2023, who had accessible information, were examined. The haemogram parameters of newborns with haemolytic disease who did not have ABO incompatibility those of newborns with ABO incompatibility and those of newborns with positive direct anti-globulin test results were compared using statistical methods. Results A total of 5,198 out of 7,780 newborns were included in the study. A total of 2582 newborns for whom demographic and laboratory values ​​could not be obtained were excluded from the study. When the data of 5,158 newborns without incompatibility and 40 newborns with haemolytic disease due to ABO incompatibility were compared, the mean red blood cell (RBC), haematocrit, haemoglobin and mean platelet volume (MPV) values of newborns with haemolytic disease were found to be statistically significantly lower than those of newborns in the control group, whereas the platelet, mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC) and red cell distribution width (RDW) values were greater. Thrombocytopenia was not observed in any patient. Conclusions Haemolytic disease due to ABO incompatibility is a mild haemolytic disease that is thought to be caused by maternal antibody density or low antigen density on neonatal erythrocytes. We detected an increase in the platelet count and a decrease in the erythrocyte count values in in the haemolytic group. Prospective studies are needed on this subject that also examine erythropoietin and thrombopoietin values.

Abstract Background Recognition of the feline red blood cell (RBC) antigen Mik and the presence of naturally occurring anti-Mik antibodies resulting in acute hemolytic transfusion reactions prompted the recommendation to perform a crossmatch before a cat's first RBC transfusion, but this guideline has not yet become a standard practice. Objective To determine the prevalence of naturally occurring non-AB alloantibodies detectable by tube crossmatch, and to compare transfusion outcomes in cats with and without a crossmatch performed. Animals Three hundred cats that received an RBC transfusion, with or without a major crossmatch performed. Methods Retrospective study. Results Major crossmatch incompatibilities were documented in 23 of 154 transfusion-naive cats (14.9%) and in 15 of 55 previously transfused cats (27%; P = 0.042). Type-specific packed RBCs (pRBCs) were administered to 167 and 82 cats with and without a crossmatch, respectively. Median volume of pRBCs administered during the first transfusion was 5.3 mL/kg (range, 2.4-18 mL/kg). Median change in PCV scaled to dose of pRBCs was +0.8%/mL/kg; administration of crossmatch-compatible pRBCs was not associated with a greater increase in PCV. Febrile transfusion reactions occurred more often in cats that received non-crossmatched (10.1%) compared to crossmatched (2.5%) pRBCs (P = 0.022). Seventy-six percent of cats that received pRBC transfusions survived to hospital discharge. A crossmatch was not associated with improved survival to discharge or at 30 or 60 days posttransfusion. Conclusions and Clinical Importance The prevalence of naturally occurring non-AB incompatibilities is sufficiently high to justify the recommendation to perform a crossmatch before all (including the first) RBC transfusions in cats.

BackgroundBecause of the severe shortage of suitable deceased donors, ABO-incompatible living donor kidney transplantation (ABOi LDKT) is performed even in pediatric recipients in Japan. We performed pediatric ABOi LDKT using rituximab without anti-A/B antibody removal.MethodsThirteen pediatric recipients (mean age 7.4, range 3.4–15.7, four females) whose baseline anti-A/B IgG titers were ≤ × 64 underwent ABOi LDKT without antibody removal and splenectomy between July 2013 and April 2017 at Toho University. Mycophenolate mofetil (MMF) was initiated on day − 10. Rituximab (100 mg) was administered twice. Basiliximab and triple maintenance immunosuppression (calcineurin inhibitor, MMF, and steroids) were administered. Protocol biopsy was performed at 3 months and 1 year after transplantation. We retrospectively compared the clinical outcomes between these recipients and 37 children (mean age 9.0, range 2.6–18.9, 15 female) who underwent ABO-compatible (ABOc) LDKT during the same period.ResultsThe mean follow-up periods of ABOi and ABOc groups were 31.9 ± 13.5 and 28.8 ± 14.4 months, respectively. In the ABOi group, no clinical acute rejection (AR) was noted and subclinical AR was observed in four patients without evidence of acute antibody-mediated rejection. In the ABOc group, clinical and subclinical AR developed in 3 and 10 patients, respectively. No significant difference was identified for the mean eGFR between the ABOi and ABOc groups (98.3 ± 48.8 vs. 86.9 ± 39.4, P = 0.452 at 3 months; 78.2 ± 21.2 vs. 79.7 ± 21.3, at 1 year, P = 0.830). Death-censored graft survival at follow-up was 100% in the ABOi group and 94.6% in the ABOc group. Patient survival during the follow-up period in both the groups was 100%. Late-onset neutropenia (LON) requiring granulocyte colony-stimulating factor occurred more frequently in the ABOi group than in the ABOc group (4 vs. 0 patients) (P < 0.001).ConclusionsPre- and post-transplantation antibody removal is not a prerequisite for successful pediatric ABOi LDKT, at least in patients with a low anti-A/B IgG antibody titer. However, LON caused by rituximab should be monitored.

BackgroundIt has traditionally been considered that mother-infant ABO incompatibility only causes mild haemolytic disease of the newborn (HDN). However, this view is inconsistent with clinical practice, and large-scale population-based data are lacking to investigate its effects on neonates.MethodsDifferences in hospitalisation rates and incidence rates of neonatal hyperbilirubinaemia (NHB) and anaemia among 47 679 Chinese liveborn neonates with different mother-infant ABO combinations, differences in the incidence of ABO-incompatible HDN (ABO-HDN) among neonates with O-B versus O-A mother-infant ABO incompatibility, and the contributions of ABO-HDN to the development of NHB and neonatal anaemia were analysed.ResultsOf the 47 679 liveborn neonates, neonates with mother-infant ABO incompatibility had higher rates of hospitalisation and incidence of NHB and anaemia. The hierarchy of the risk of mother-infant ABO incompatibility to the neonate was O-B > O-A > non-O-A/O-B incompatibility. Among neonates with O-B and O-A mother-infant ABO incompatibility, the ABO-HDN incidence rates were 15.27% (513/3359) and 11.33% (417/3680), respectively (95% CI 1.41 (1.23 to 1.62)), and the severe ABO-HDN incidence rates were 2.05% (69/3359) and 1.14% (42/3680), respectively (95% CI 1.82 (1.23 to 2.67)). Among the 7039 neonates with O-A/O-B mother-infant ABO incompatibility, ABO-HDN was an independent aetiological factor in 41.11% (666/1620) of the neonates with NHB, 70.27% (52/74) of the neonates with severe NHB, 42.34% (163/385) of the neonates with anaemia and 18.28% (17/93) of the neonates with severe anaemia.ConclusionsMother-infant ABO incompatibility often leads to severe HDN and is a dominant cause of NHB and neonatal anaemia, leading to significantly higher neonatal hospitalisation rates.

Objectives We assessed the value of the diffusion-weighted image (DWI) for predicting intrahepatic biliary complications (IHBC) after ABO-incompatible liver transplantation (ABOi-LT), potentially leading to refractory cholangitis. Materials and methods In this retrospective study at a single center, 56 patients who underwent ABOi-LT from March 2021 to January 2023 were analyzed. All received magnetic resonance cholangiopancreatography (MRCP) and DWI during the postoperative hospitalization. MRCP findings, including bile duct DWI hyperintensity, were assessed. Participants suspected of having a biliary infection or obstructive jaundice underwent endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic biliary drainage (PTBD) during the follow-up. Non-anastomotic biliary strictures on cholangiography were classified as IHBC, as either perihilar or diffuse form. DWI hyperintensity was compared between groups with and without IHBC. Logistic regression analysis was performed to identify independent risk factors for IHBC. Results Of the 55 participants (median age 55 years, 39 males), IHBC was diagnosed in eight patients over a median follow-up of 15.9 months (range 5.6–31.1). Bile duct DWI hyperintensity was observed in 18 patients. Those with DWI hyperintensity exhibited a higher IHBC incidence (6/18, 33.3% vs. 2/36, 5.6%; p  = 0.01), and more frequently developed the diffuse type IHBC (4/18, 22.2% vs. 1/36, 2.8%; p  = 0.04). Regression analysis indicated that bile duct DWI hyperintensity is an independent risk factor for IHBC (odds ratio (OR) 10.1; 95% confidence interval (CI) 1.4, 71.2; p  = 0.02) and its diffuse form (OR 15.3; 95% CI 1.2, 187.8; p  = 0.03). Conclusion Postoperative DWI hyperintensity of bile ducts can serve as a biomarker predicting IHBC after ABOi-LT. Clinical relevance statement Postoperative diffusion-weighted image hyperintensity of the bile duct can be used as a biomarker to predict intrahepatic biliary complications and aid in identifying candidates who may benefit from additional management for antibody-mediated rejection. Key Points Intrahepatic biliary complications following ABO-incompatible liver transplantation can cause biliary stricture and biloma formation. Bile duct hyperintensity on early postoperative diffusion-weighted imaging was associated with increased intrahepatic biliary complication risk. This marker is an additional method for identifying individuals who require intensive management to prevent complications.

Blood transfusion safety depends on swift blood compatibility testing. Alloantibodies recognizing these blood group antigens determine blood compatibility, and the transfusion of incompatible blood can lead to life‐threatening hemolytic transfusion reactions. Recently, the landscape of blood compatibility testing has been complicated due to the interference caused by therapeutic antibodies targeting CD38, a key target in cancer immunotherapy that is also expressed on red blood cells. The presence of anti‐CD38 antibodies in blood samples has been found to bind to test or donor red blood cells, resulting in false positive tests. This interference poses a serious risk as it can potentially mask immunogenic alloantibodies and cause delays in supplying safe blood products. We present the development and application of fragment crystallizable (Fc)‐fusion constructs, referred to as “baitbodies”, designed to neutralize anti‐CD38 antibodies and mitigate false positive test outcomes. The extracellular domain of CD38 was fused to the Fc domain of a murine immunoglobulin G. These baitbody constructs were thoroughly characterized and applied in both serological microcolumn agglutination and automated solid‐phase red cell adherence assays. The CD38‐mFc baitbody successfully prevented agglutination reactions induced by three clinically relevant anti‐CD38 monoclonal antibodies—daratumumab, felzartamab and isatuximab—in spiked samples. This allowed the detection of alloantibodies of the Rhesus, Kell and Duffy blood groups without interference. The CD38‐mFc construct also demonstrated potential in a head‐to‐head comparison with commercial mitigation reagents, DaraEx and Grifols sCD38. Finally, the CD38‐mFc baitbody effectively neutralized daratumumab in patient samples, preventing false positive test outcomes.

Key Points ABO-incompatible (ABOi) kidney transplantation is now an established treatment option for patients with end-stage renal disease, but the mechanisms that underlie acceptance of ABOi grafts are not well understood The biology of the ABO system is complex; blood group subtypes and organ-specific patterns of core-chain tissue distribution require particular consideration in the context of ABOi transplantation Innovative humanized animal models are expected to provide a better understanding of anti-A/B immune responses and might help to establish innovative therapeutic strategies to counteract blood-group-specific B-cell responses The development of efficient desensitization protocols including apheresis, modulation of B-cell immunity and long-term maintenance immunosuppression has enabled ABOi kidney transplantation to become a safe treatment strategy with favourable outcomes Although the reduction of pretransplant anti-A/B antibody titres below a permissive threshold is a major principle of desensitization, thresholds at which antibody-mediated damage can be predicted have not been defined Tailoring the intensity of preconditioning for ABOi kidney transplant recipients according to their pretransplant anti-A/B antibody titres might be an efficient strategy to minimize the risks associated with enhanced immunosuppression The development of effective desensitization strategies has enabled ABO incompatible (ABOi) kidney transplantation to become an established treatment option for patients with end-stage renal disease. Here, the authors review the mechanisms that underlie acceptance and rejection of ABOi grafts, recipient desensitization strategies, patient outcomes and novel treatment strategies that might promote graft acceptance and enable minimization of immunosuppression. Kidney transplantation across the ABO blood group barrier was long considered a contraindication for transplantation, but in an effort to increase donor pools, specific regimens for ABO-incompatible (ABOi) transplantation have been developed. These regimens are now widely used as an integral part of the available treatment options. Various desensitization protocols, commonly based on transient depletion of preformed anti-A and/or anti-B antibodies and modulation of B-cell immunity, enable excellent transplant outcomes, even in the long-term. Nevertheless, the molecular mechanisms behind transplant acceptance facilitated by a short course of anti-humoral treatment are still incompletely understood. With the evolution of efficient clinical programmes, tailoring of recipient preconditioning based on individual donor–recipient blood type combinations and the levels of pretransplant anti-A/B antibodies has become possible. In the context of low antibody titres and/or donor A 2 phenotype, immunomodulation and/or apheresis might be dispensable. A concern still exists, however, that ABOi kidney transplantation is associated with an increased risk of surgical and infectious complications, partly owing to the effects of extracorporeal treatment and intensified immunosuppression. Nevertheless, a continuous improvement in desensitization strategies, with the aim of minimizing the immunosuppressive burden, might pave the way to clinical outcomes that are comparable to those achieved in ABO-compatible transplantation.

Increased red blood cell (RBC) transfusion requirements are associated with morbidity and mortality after allogeneic hematopoietic cell transplantation. However, its impact on the outcomes after cord blood transplantation (CBT) is unclear. We retrospectively analyzed the data of 278 adult patients who received single-unit CBT in our institute. The median number of RBC transfusions for each patient was 12 units (range, 4–66) by day 30 and 14 units (range, 4–70) by RBC engraftment. Sex, cord blood CD34+ cell dose, cytomegalovirus serostatus, total body irradiation dose in the conditioning regimen, ABO blood group incompatibility, and pre-CBT RBC transfusion requirements were significantly associated with the number of RBC transfusion units in the linear regression analysis. In the multivariate analysis, RBC transfusion ≥18 units by day 30 was significantly associated with higher overall mortality (hazard ratio, 1.86; P = 0.018). These data suggested that early RBC transfusion burden was significantly associated with overall mortality in adult patients undergoing single CBT. Early RBC transfusion burden might be a surrogate marker for poor outcomes after single CBT.