In 2012, the International Society of Blood Transfusion (ISBT) formalized the JR blood group system (ISBT 032), with Jra (ISBT 032001) as its only antigen. Jra is located on a multipass membrane glycoprotein named ABCG2. ABCG2, or ATP-binding cassette subfamily G member 2, is also known as breast cancer resistance protein (BCRP) or CD338. This glycoprotein participates in various physiological, biochemical and metabolic processes in the human body. It is encoded by the ABCG2 gene, located on chromosome 4. In recent years, the ABCG2 gene variants have been gradually unraveled through the deeper study of the JR blood group system. Meanwhile, the JR blood group system is clinically important, being associated with fetal and neonatal anemia, hydrops fetalis, neonatal jaundice, hemolytic disease of the fetus and newborn (HDFN), and hemolytic transfusion reaction (HTR). Furthermore, its carrier molecule, ABCG2, is associated with hyperuricemia/gout and mirror syndrome. In addition, ABCG2 plays an important regulatory role in a variety of physiological and pathological processes, such as the regulation of uric acid metabolism, the maintenance of folate and porphyrin homeostasis, the regulation of blood-brain barrier substance exchange, and the regulation of anti-tumor drug transport and drug resistance. This study reviews the distributional characteristics, molecular biological features, immunological features and clinical significance of the JR blood group system and ABCG2.

Massive transfusion protocols are essential in trauma resuscitation but may inadvertently increase the risk of acute hemolytic transfusion reactions (AHTRs), which are typically caused by ABO incompatibility. Recognition is difficult because signs of hemolysis can mimic trauma-related hemorrhage or coagulopathy. Cognitive biases in emergency decision-making may further delay diagnosis. Although ABO-incompatible AHTR remains exceptionally rare in trauma, it is easily overlooked in the context of polytrauma. We describe three cases of ABO-incompatible AHTR admitted to a tertiary trauma center. First, a 52-year-old man with multiple injuries received three mis-issued AB+ units instead of group O blood. He developed hemoglobinuria, coagulopathy, and fatal multiorgan failure. The second case involved an 81-year-old man with multiple comorbidities who underwent hip fracture fixation; due to a mislabeled admission sample, he received A+ instead of B+ blood, resulting in persistent anemia, renal failure, and death. The third case was a 30-year-old woman with severe head and thoracic trauma who received incompatible blood under an emergency release protocol. She developed hemolysis, neurologic decline, and sepsis, and ultimately died of multiorgan failure. In all three patients, early post-transfusion anemia and hemodynamic instability were attributed to trauma, delaying recognition of hemolysis. AHTR may therefore be overlooked in trauma settings, where its manifestations overlap with injury-related complications and cognitive biases such as anchoring and premature closure may impair diagnostic reasoning. Strict transfusion safety protocols, heightened vigilance when hemoglobin levels fail to rise, and awareness of cognitive errors may improve early recognition and patient outcomes.

Hereditary spherocytosis (HS) is a common inherited cause of hemolytic anemia and is most often diagnosed in childhood. While the condition does not by itself disqualify affected adults from military service, its autosomal dominant inheritance has important implications for offspring, who may develop more severe disease. We report the case of a 38-year-old active-duty US Army soldier of Saipanese (Chamorro) descent who presented with persistent, unexplained fatigue -- most pronounced during strenuous physical activity -- despite adequate sleep. He had no formal family history of anemia, although one of his three children carries an undiagnosed anemia. Physical examination revealed splenomegaly. Laboratory evaluation demonstrated compensated hemolysis, as evidenced by a low-normal hemoglobin maintained by a reticulocyte response of 9.36%, a normal mean corpuscular volume, an elevated mean corpuscular hemoglobin concentration of 36.7 g/dL -- a characteristic diagnostic feature of HS -- an elevated red cell distribution width, undetectable haptoglobin, and elevated lactate dehydrogenase and indirect bilirubin. The peripheral blood smear was reported by the staff pathologist as a normocytic, normochromic anemia with occasional spherocyte-like forms and mild polychromasia. The patient also demonstrated mild-to-moderate hepatic iron overload despite the absence of transfusions. Genetic testing identified a heterozygous nonsense mutation in the SPTB gene, c.2175G>A (p.Trp725Ter), introducing a premature termination codon within exon 12 and consistent with HS type II. A concurrent pyruvate kinase variant of uncertain significance was also identified. The variant identified in our patient was subsequently deposited in ClinVar by the clinical testing laboratory (Variation ID: 2428713; classified pathogenic) and is absent from gnomAD v4.1.1; to our knowledge, this variant has not previously been described in the published clinical literature. This report provides the clinical and phenotypic characterization of the patient whose testing contributed to that ClinVar submission, and highlights the value of genetic evaluation in adults with unexplained hemolysis, particularly when the offspring is also affected.

Hemoplasmas are Gram-negative bacteria that can cause hemolytic anemia in a variety of mammalian species, including non-human primates. This study investigated the molecular prevalence and genetic characteristics of hemoplasmas in free-ranging long-tailed macaques in three previously unreported provinces in southern Thailand. In total, 210 blood samples were collected from long-tailed macaques in Phang Nga, Phetchaburi, and Satun provinces. DNA was extracted from the blood samples and screened for hemoplasmas using a broad-range nested polymerase chain reaction (PCR) assay targeting the 16S rRNA gene. Positive samples were sequenced for species identification, and phylogenetic analysis was performed to determine their genetic relationships. Overall, 35.7% (75/210; 95% CI = 29.2-42.6%) of the samples tested positive for hemoplasmas. Sequence analysis showed 99.3-100.0% identity with Candidatus Mycoplasma haematomacacae. Phylogenetic analysis confirmed that all sequences clustered within the Ca. M. haematomacacae clade, together with other reported isolates from macaques in several countries, including Thailand. In conclusion, this study has provided molecular evidence of Ca. M. haematomacacae infection in long-tailed macaques in areas where such infections had not been previously reported. Based on the results of this study, long-tailed macaques in various regions of Thailand might be infected with and act as reservoirs for this pathogen.

Massive splenomegaly refers to a marked and clinically significant enlargement of the spleen beyond normal limits. Although uncommon, it is clinically significant because it may be associated with hematologic, infectious, infiltrative, malignant, or portal hypertensive disorders. Chronic hemolytic anemias are a recognized cause of marked splenic enlargement due to persistent erythrocyte destruction and reticuloendothelial hyperplasia. Ongoing hemolysis also increases bilirubin production, predisposing patients to pigment gallstone formation and biliary tract disease. We report the case of a 29-year-old male who presented with jaundice and imaging findings consistent with choledocholithiasis. His medical history was notable for chronic hemolytic anemia and recurrent episodes of jaundice. Magnetic resonance cholangiopancreatography confirmed common bile duct stones and marked splenomegaly. The patient underwent exploratory laparotomy with splenectomy and common bile duct exploration followed by choledochoduodenal anastomosis. Intraoperatively, a massively enlarged spleen and hepatomegaly were identified. Significant bleeding from the splenic pedicle required vascular control and a blood transfusion. The postoperative course was favorable, with progressive reduction in bilirubin levels and no evidence of further complications. Histopathological examination demonstrated a congestive spleen with extensive hemorrhagic areas. This case highlights the importance of a multidisciplinary approach in the evaluation and management of massive splenomegaly and illustrates that timely surgical treatment can achieve satisfactory outcomes in selected patients.

Thrombotic microangiopathy (TMA) is an acute syndrome characterized by microangiopathic hemolytic anemia, thrombocytopenia, and ischemic end-organ damage resulting from platelet-rich microthrombi obstructing the microvasculature. The kidney is particularly vulnerable to TMA-mediated injury due to its numerous microvessels, often leading to acute kidney injury (AKI). AKI induced by TMA can manifest in oncological conditions, although infrequently. Rectal cancer presenting with TMA-related AKI as the initial manifestation is even rarer, posing a diagnostic challenge for nephrologists. We describe a 62-year-old man admitted with AKI followed by severe thrombocytopenia and anemia. During the diagnostic workup to exclude thrombotic thrombocytopenic purpura, the patient achieved complete hematological recovery after hemodialysis and plasma exchange (PEX), which enabled the performance of a renal biopsy. The underlying etiology was TMA on renal biopsy. However, persistent elevation of lactate dehydrogenase and new‑onset of bone pain prompted further evaluation. The magnetic resonance imaging scan and positron emission tomography-computed tomography subsequently confirmed rectal cancer with bone and liver metastases. This case illustrates that AKI secondary to cancer-related TMA may present as the initial clinical manifestation of an underlying malignancy. Renal biopsy plays a crucial role in establishing a definitive diagnosis and guiding subsequent management. Furthermore, PEX was associated with hematological improvement in this patient, but its overall clinical benefit remains to be determined as the patient remained dialysis‑dependent.

Autoimmune hemolytic anemia (AIHA) is an uncommon but recognized complication of intravenous immunoglobulin (IVIG) therapy in Kawasaki disease (KD). The mechanism is thought to involve passive transfer of donor isohemagglutinins that bind to recipient red blood cell (RBC) antigens, causing immune-mediated hemolysis. We describe four pediatric cases of IVIG-induced AIHA following treatment for KD. We retrospectively reviewed four KD patients who developed hemolytic anemia temporally associated with IVIG administration. Clinical data included age, blood type, transfusion requirement, and outcomes. All four patients were non-O blood types. Hemolysis developed within days of IVIG infusion, confirmed by a positive direct antiglobulin test. Two patients required red blood cell transfusions for symptomatic anemia. The lowest recorded hemoglobin levels ranged from 6.6 to 7.9 g/dL. None required corticosteroids or additional immunosuppression. All patients achieved full recovery with iron and folate supplementation. No coronary aneurysms or long-term complications were observed. IVIG-induced AIHA is a rare but clinically significant complication of KD therapy, particularly in non-O blood group patients. Routine post-infusion hemoglobin monitoring and early recognition of anemia are essential. Supportive management alone is typically sufficient, and prognosis remains excellent when the condition is promptly identified and managed.

Prior surveys of chronic automated red blood cell exchange (RCE) for patients with sickle cell disease (SCD) have identified considerable procedural variability, especially with the use of isovolemic hemodilution red blood cell exchange (IHD-RCE). We conducted a survey of chronic RCE practices among American Society for Apheresis (ASFA) members to identify opportunities for practice harmonization and future studies. The ASFA SCD Research Subcommittee developed a 72-item survey of chronic RCE practices, with a focus on IHD-RCE. The survey was validated internally and distributed by email to all ASFA members from September 2024 to February 2025. One survey response from each institution was retained for data analysis. Descriptive statistics were performed. Sixty-two survey responses, including three from international institutions, were retained for analysis. Sixty-one percent of respondents (38/62) reported using at least one fixed RCE target, with end hematocrit being the most common fixed parameter (40%, 25/62), followed by fraction of cells remaining (31%, 19/62) and hemoglobin S% (27%, 17/62). Most respondents (60%, 37/61) performed IHD-RCE at their institution, though other details such as the minimum hematocrit, exclusion criteria, and response to adverse effects were variable. Consistent pre- and post-RCE laboratory monitoring practices were reported. Consistent with earlier surveys, procedural variability in chronic RCE practices for patients with SCD is observed. This highlights opportunities to compare outcomes where practice variability exists. Consensus guidelines based on institutional practices with optimal outcomes should be developed.

Objective: To summarize current evidence on the use of buprenorphine for chronic pain management in individuals with sickle cell disease (SCD) and identify gaps for future research.