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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.

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.

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.

BACKGROUND: There is a markedly reduced half‐life of transfused RBCs when donor and recipient cats or humans are cross‐match incompatible. Only 10–20% of horses have naturally occurring alloantibodies. Therefore, cross‐match testing before blood transfusion is not always performed. HYPOTHESIS: Cross‐match incompatibility predicts shortened RBC survival time as compared to that of compatible or autologous blood. ANIMALS: Twenty healthy adult horses. METHODS: Prospective trial. Blood type, anti‐RBC antibody screen (before and 1 month after transfusion) and major and minor cross‐match determined 10 donor‐recipient pairs. Two pairs were cross‐match compatible, the remainder incompatible. Donor blood (4 L) was collected into citrate phosphate dextrose adenine‐1, labeled with NHS‐biotin, and transfused into recipients. Samples were collected at 1 hour and 1, 2, 3, 5, 7, 14, 21, 28, and 35 days after transfusion, and biotinylated RBCs were detected by flow cytometry. Horses were monitored for transfusion reaction during transfusion and daily for 5 days. RESULTS: Cross‐match incompatibility was significantly associated with decreased RBC survival time (P < .001). The half‐life of transfused incompatible (cross‐match >1+) allogenic equine RBCs was 4.7 (95% CI, 3.2–6.2) days versus 33.5 (24–43) days for compatible pairings. Cross‐match incompatibility was associated with acute febrile transfusion reaction (P = .0083). At day 30, only 1 horse had developed novel anti‐RBC antibodies. CONCLUSIONS AND CLINICAL IMPORTANCE: Cross‐match incompatibility was predictive of febrile transfusion reaction and shortened transfused RBC survival, but did not result in production of anti‐RBC antibodies at 30 days. Cross‐match testing before transfusion is recommended.

ABO blood type incompatibility hemolytic disease of newborn (ABO-HDN) and drug-induced immune hemolytic anemia (DIIHA) due to non-immunologic protein adsorption (NIPA) mainly cause extravascular hemolysis. All the reported severe DIIHA were caused by drug-induced antibodies, and rare report of acute intravascular hemolysis was caused by the NIPA mechanism or ABO-HDN. We report the first case of acute intravascular hemolysis induced by cefotaxime sodium - sulbactam sodium (CTX - SBT) in a case of ABO-HDN which resulted in death at 55 h after birth. The mother's blood type was O and RhD-positive, and the newborn's blood type was B and RhD-positive. No irregular red blood cell (RBC) antibodies or drug-dependent antibodies related to CTX or SBT was detected in the mother's plasma and the plasma or the RBC acid eluent of the newborn. Before the newborn received CTX - SBT treatment, the result of direct antiglobulin test (DAT) was negative while anti-B was positive (2 +) in both plasma and acid eluent. After the newborn received CTX - SBT treatment, the results of DAT for anti-IgG and anti-C3d were both positive, while anti-B was not detected in plasma, but stronger anti-B (3 +) was detected in acid eluent. experiments confirmed that NIPA of SBT promoted the specific binding of maternal-derived IgG anti-B to B antigen on RBCs of the newborn, thereby inducing acute intravascular hemolysis. The NIPA effect of SBT promoted the specific binding of mother-derived IgG anti-B in newborn's plasma to the newborn's RBC B antigens and formed an immune complex, and then activated complement, which led to acute intravascular hemolysis. Drugs such as SBT with NIPA effect should not be used for newborns with HDN.

ObjectivesTo evaluate CT findings of biliary strictures in ABO-incompatible living donor liver transplantation (LDLT) recipients, with emphasis on associated 1-month post-transplantation CT findings, and evaluate clinical outcomes.MethodsOf 351 ABO-incompatible recipients, we retrospectively evaluated CT scans in 65 recipients with biliary stricture. The biliary strictures on CT scans were classified as type A (perihilar) and type B (diffuse). Precedent CT abnormality patterns and the presence of a periportal halo sign at 1-month post-transplantation were evaluated. For each patient, clinical outcomes were evaluated.ResultsOf 65 ABO-incompatible recipients with biliary strictures, 36.9% had type B strictures. Compared with biliary strictures at diagnosis, similar CT abnormality patterns were observed for 84.4% in type A and 86.4% in type B strictures at 1-month post-transplantation. Complex periportal halo signs on the 1-month post-transplantation CT were more frequently noted for type B than type A strictures (86.4% vs. 3.1%, P < 0.001). Progressive clinical outcomes were more frequently observed for type B than type A strictures (79.2% vs. 26.8%, P < 0.001), with a significantly shorter graft survival time (46.4 months vs. 90.8 months, P < 0.001).ConclusionCT abnormality patterns and complex periportal halo signs on 1-month post-transplantation CT may be clinically useful for managing biliary strictures in ABO-incompatible LDLT recipients.Key Points• Of ABO-incompatible LDLT recipients, type B biliary stricture incidence was 6.8%.• Of type B strictures, 86.4% exhibited similar CT abnormality patterns at 1-month post-transplantation.• Complex periportal halo at 1 month was significantly associated with type B strictures.• Progressive clinical outcomes were more frequently observed in type B strictures.

Severe transfusion-related acute lung injury (TRALI) is often due to antibodies in blood components directed against human neutrophil antigen (HNA)-3a. This study aimed to report the genotype frequencies of the HNA-3 system and to estimate the potential risk of HNA-3 incompatibility and alloimmunization in two Thai populations. Eight hundred DNA samples obtained from 500 unrelated healthy blood donors at the National Blood Centre, Thai Red Cross Society, Bangkok and 300 samples from the Blood Bank, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand were included. HNA-3 genotyping was performed using an in-house polymerase chain reaction with sequence-specific primer (PCR-SSP) technique. The observed frequencies of the HNA-3a/3a, HNA-3a/3b, and HNA-3b/3b genotypes were 0.528, 0.380, and 0.092 in central Thais and 0.600, 0.350, and 0.050 in northern Thais, respectively. The frequencies were used to estimate HNA-3 incompatibility and risk of HNA-3a alloimmunization. The HNA-3 incompatibility in central Thais (33.28%) was higher than northern Thais (28.75%), corresponding to a significantly higher probability of HNA-3a alloimmunization (P<0.05) similar to Japanese and Chinese populations. This study showed the high risk of HNA-3 incompatibility and alloimmunization, especially in central Thai blood donors. A molecular-based identification of the HNA-3 genotype of female donors is suggested to reduce the risk of TRALI following plasma and whole blood allogeneic transfusion.

Background/AIMS: We investigated the impact of the baseline anti-A/B antibody titer on the clinical outcome in ABO-incompatible kidney transplantation (IKT). Methods: We included 183 patients who had undergone KT (40 ABO IKT and 143 ABO-compatible KT). Eight patients with a baseline titer of ≥1:512 were assigned to the high-titer group and 32 patients with a baseline titer of ≤1:256 were assigned to the low-titer group. Patients who underwent ABO-compatible KT were used as the control group. We compared the clinical outcomes of the three groups. Results: Before transplantation, the high-titer group displayed more frequent antibody rebound, as shown in a lower titer reduction rate, and more difficulty reaching the target titer (1:16) than the low-titer group. During the postoperative period and out-clinic follow-up, antibody rebound was more frequent, and the rate of acute rejection and infection were significantly higher and allograft function was lower in the high-titer group than in the low-titer and control groups. Multivariate analysis showed that high baseline antibody titer was an independent risk factor for acute rejection. Conclusion: ABO IKT in the high-titer group (baseline titer ≥1:512) required greater caution compared to the low-titer group because of the higher tendency of antibody rebound and the risk for acute rejection. © 2013 S. Karger AG, Basel [PUBLICATION ABSTRACT]