The purpose of this study was to clarify the characteristics of newly diagnosed systemic lupus erythematosus (SLE) patients with or without kidney involvement in Japan. We used electronic data of SLE patients in the National Database of Designated Intractable Diseases of Japan who newly registered between 2015 and 2017. We analyzed patients within one year of disease onset. Kidney involvement was defined as any of the following: urinary protein ≥ 0.5g/day, granular casts, a clinical diagnosis of nephrotic syndrome, acute or chronic renal failure, or rapidly progressive glomerulonephritis, an estimated glomerular filtration rate (eGFR) < 60mL/min/1.73 m2, lupus nephritis confirmed by renal biopsy, or hemodialysis. Among 2315 SLE patients, 1088 (47.0%) had kidney involvement. Patients with kidney involvement more frequently exhibited symptoms such as pulmonary hemorrhage, pulmonary infarction and disturbance of consciousness, pericarditis, and hemolytic anemia whereas manifestations such as arthritis, aseptic meningitis, discoid rash, photosensitivity, and Raynaud's phenomenon were less common compared with those without kidney involvement. Anti-DNA antibody positivity was higher and complement levels (C3, C4, and CH50) were lower in patients with kidney involvement. In addition, concomitant glucocorticoid pulse therapy and immunosuppressive drugs were more frequently used in patients with kidney involvement. In this nationwide cohort, nearly half of newly diagnosed Japanese patients with SLE had kidney involvement and showed a distinct pattern of systemic manifestations, autoantibody profiles, and treatment intensity. These findings provide important insights into the epidemiology and pathophysiology of kidney involvement in SLE in Japan.

Anemia results from imbalanced hemoglobin or red blood cell production and clearance. Hemolytic anemia, caused by premature red blood cell removal, can be intravascular (in blood) or extravascular (erythrophagocytosis). Hemolysis is common in Sickle Cell Disease (SCD) and Beta-Thalassemia anemia (β-thalassemia), the most prevalent inherited hemolytic anemias. Hemolysis severity is primarily assessed by measuring indirect serum biomarkers such as lactate dehydrogenase, released by cytolysis, bilirubin and haptoglobin. However, these markers do not directly indicate either the cause or the primary site of hemolysis. We introduced a novel plasma heme assay that quantifies all heme-related species in plasma, including hemoglobin, methemoglobin, heme, and hemopexin. Our findings revealed a more profound intravascular red blood cell destruction in SCD compared to β-thalassemia as demonstrated by higher values of plasma hemoglobin, respectively 6.20 and 2.52 μM (p < 0.001), with significant inter-individual variability. In contrast, β-thalassemia patients exhibited higher plasma heme values (11.00 μM vs. 1.51 μM; p < 0.0001) reflecting a probable mixed origin (dyserythropoiesis and hemolysis). Plasma hemopexin was negatively correlated with plasma heme in all patients. Plasma heme exceeded hemopexin scavenging capability in 72% of β-thalassemia and 36% of SCD patients. In β-thalassemia, plasma heme levels were significantly higher in transfusion-dependent compared to non-transfusion-dependent patients, indicating that excess heme reflects clinical severity. In SCD, elevated concentration of excess heme was associated with a significant increased risk of mortality compared to LDH or reticulocytes%. This novel spectral assay offered significant benefits for diagnosis, treatment, and patient management.

Nitrofurantoin-induced immune-mediated vasculitis with auto-immune haemolytic anaemia and pigment nephropathy: A rare adverse drug reaction.

Autoimmune hemolytic anemia (AIHA) is uncommon in the pediatric population, particularly when it manifests as severe anemia. AIHA is characterized by a positive direct antiglobulin test (DAT) and immune-mediated red blood cell (RBC) destruction. AIHA is subclassified on the basis of the thermal characteristics of autoantibody into warm, cold, and mixed. Mixed AIHA shows both the common types and characteristics of warm and cold types. A 14-year-old male, born of nonconsanguineous marriage, admitted with complaints of dizziness and hematuria. It was not associated with decreased urine output and abdominal pain. The child had a similar type of history 2 years back for that, he was treated with a 3-unit-packed RBC transfusion. On examination marked pallor, icterus and mild splenomegaly were present. Diagnosis of mixed AIHA was done on the basis of a DAT and was 4+ positive against Ig G and C3d. In cold, an agglutination test was done which was > 1:64 in titer. In peripheral blood smear, at below 37°C, it denoted the clumping of RBC with polychromasia, which is not reversed at room temperature. The child was treated with broad spectrum antibiotics, multiple-packed RBC transfusion, and injection methyl prednisolone. In follow-up, the child's clinically improved but DAT for immunoglobulin G remained positive and prednisolone was tapered to a maintenance dose of 0.5 mg/kg on alternate days. Mixed AIHA in pediatrics is an extremely rare disease, especially when presenting with severe anemia. It is very difficult to diagnose and treat. Hence, detailed clinical and extensive laboratory workup is required to diagnose the case. Clinical presentation of mixed AIHA, other than acute hemolysis, may manifest as blood group cross-match incompatibility, which is challenging for pathologists and awareness of this occurrence is essential for clinicians. A case of mixed AIHA should be treated with steroids immediately along with supportive care of packed RBC transfusion with the least incompatibility and long-term follow-up is required to improve outcome.

Snakebite envenomation is a global public health concern, and hemotoxic bites can lead to severe coagulopathy, microangiopathic hemolytic anemia, and compartment syndrome. We describe a previously healthy 6-year-old boy who presented with progressive left lower limb swelling, discoloration, and bleeding from intravenous cannula sites following a snakebite sustained in rural Pakistan, consistent with severe hemotoxic envenomation. Despite antivenom and transfusion support, he developed persistent venom-induced consumption coagulopathy with hypofibrinogenemia, markedly prolonged clotting times, thrombocytopenia, and features of microangiopathic hemolytic anemia. Severe limb swelling raised concern for compartment syndrome; however, fasciotomy was deferred due to the high risk of bleeding in the setting of uncontrolled coagulopathy. Transferred to Bahrain, he underwent five sessions of therapeutic plasma exchange, initiated due to ongoing clinical and laboratory deterioration, resulting in stabilization of hematologic parameters, resolution of limb swelling, and preservation of limb function. This case highlights the role of plasma exchange in children unresponsive to conventional therapy and demonstrates that conservative management of suspected compartment syndrome may be feasible when surgical intervention carries significant risk, underscoring the importance of early recognition and multidisciplinary care in complex pediatric envenomation.

Sutimlimab is a monoclonal antibody against complement fraction C1s approved for the treatment of hemolytic anemia due to cold agglutinin disease (CAD). Here, we analyzed and report the largest international CAD cohort of sutimlimab-treated patients ever reported to highlight its safety and effectiveness in the real-world setting. We accrued a cohort of 57 CAD patients (median age 73.5 years, 56% females). At baseline, patients had severe to moderate anemia (median Hb 8.9 g/dL) and active hemolysis, with a substantial transfusion burden despite a median of 2 prior therapies, including corticosteroids and rituximab. After sutimlimab initiation, median Hb increased by 2 g/dL within 2 weeks and reached 12 g/dL in 4 weeks, remaining stable up to 24 months. This improvement was paralleled by an early and durable normalization of hemolytic markers. Objective responses were observed in most patients by week 2, with complete responses in approximately 50% by Week 4 and 55%-60% during long-term follow-up. Peripheral cold-induced symptoms did not improve and were associated with reduced response rates. Inadequate reticulocytosis also predicted poorer response and suggests the combination with recombinant erythropoietin. Sutimlimab was generally well tolerated. Infections were the most frequent adverse events (23%); severe infections predominantly occurred in previously rituximab-treated individuals. Hemolytic exacerbations occurred in 16% of cases, mostly due to infections. Thrombotic complications were rare. Overall, sutimlimab demonstrated rapid, durable effectiveness and a favorable safety profile in heavily pretreated real-world CAD patients.

Exchange transfusion remains the definitive treatment for severe neonatal hyperbilirubinaemia; yet its aetiology and outcomes in rural tropical settings are poorly characterised. This five-year retrospective analysis of 58 neonates at a North Indian rural tertiary centre reveals that Rh incompatibility accounted for 76% of cases - a striking divergence from high income-country patterns where ABO incompatibility predominates - indicating critical gaps in antenatal Rh immuno-prophylaxis. The procedure achieved a mean bilirubin reduction of 50% (424 ± 106 to 212 ± 70&mu/L, p < 0.001) with no procedure-related mortality, though clinically significant adverse events occurred in 19% of neonates. Notably, 10.2% presented with acute bilirubin encephalopathy at the time of intervention, representing potentially preventable neurological injury. These findings make a compelling case for urgent, systematic improvements in antenatal screening, Rh immuno-prophylaxis access, and early jaundice recognition in tropical resource-limited settings.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common inherited enzymatic disorder that may result in acute hemolytic anemia when affected individuals are exposed to specific triggers. Adequate parental knowledge and appropriate attitudes are essential for prevention and early management. This study aimed to assess parents' knowledge, attitudes, and practices (KAP) toward G6PD deficiency. A descriptive cross-sectional study was conducted among parents attending the pediatric outpatient department of Saqr Hospital, Ras Al Khaimah, UAE. Participants were recruited using convenience sampling. Data were collected at a single point in time using a validated questionnaire assessing demographic characteristics, KAP related to G6PD deficiency. The collected data were analyzed using standard statistical methods. A total of 350 participants were included in the study. The study population had a mean age of 39.32 (standard deviations = 9.08). Majority were females (88%), married (94.2%), Emirati (72.5%), and had a bachelor's degree or higher (61.1%). Only 7.43% of parents demonstrated good knowledge, whereas 44.00% showed a good attitude toward G6PD deficiency. Male gender was significantly associated with good knowledge ( P = 0.001), while no factors were associated with good attitude. This study demonstrates substantial gaps in parental knowledge regarding G6PD deficiency despite relatively better attitudes toward preventive practices. Targeted educational strategies focusing on inheritance, triggers, and clinical features are warranted to improve awareness and reduce preventable complications.

Disseminated carcinomatosis of the bone marrow (DCBM) is a rare complication of advanced malignancies that may present with microangiopathic hemolytic anemia (MAHA). A 65-year-old man with esophageal adenocarcinoma was admitted due to melena and severe anemia, initially suspected to be caused by tumor bleeding. However, persistent anemia despite multiple transfusions and the presence of schistocytes on a peripheral blood smear suggested MAHA. A bone marrow biopsy revealed cytokeratin-positive tumor cells, confirming the diagnosis of DCBM. Chemotherapy with S-1, oxaliplatin, and trastuzumab improved hemolysis and achieved transfusion independence. Clinicians should consider cancer-related MAHA when the degree of anemia is disproportionate to the amount of bleeding in patients with advanced cancer.

Sutimlimab vs B-cell-targeted therapy in cold agglutinin disease: which is the optimal approach?

We present two cases of Evans syndrome (ES) during durvalumab monotherapy after combination chemotherapy with durvalumab for advanced hilar cholangiocarcinoma. The patients were men aged 71 and 73 years with satisfactory performance status. They received eight cycles of gemcitabine, cisplatin, and durvalumab, followed by durvalumab monotherapy (five and six cycles, respectively) for a total of approximately 11 months. Subsequently, they developed autoimmune hemolytic anemia, characterized by reticulocytosis, indirect hyperbilirubinemia, elevated lactate dehydrogenase levels, and a positive direct Coombs test. Furthermore, their condition met the diagnostic criteria for ES, as they developed concomitant thrombocytopenia with antiplatelet antibodies. Both patients demonstrated hematological recovery with corticosteroid therapy, highlighting the efficacy of immunosuppression in managing this rare hematologic immune-related adverse event. Notably, the onset occurred during maintenance therapy after a prolonged latency of 11 months, underscoring the potential for delayed hematologic immune-related adverse events with programmed death-ligand 1 blockade. Corticosteroids remain the cornerstone of treatment, and high-dose pulse therapy may be necessary in refractory cases. In conclusion, recognition of durvalumab-induced ES is crucial for appropriate management.

We report a 33-year-old woman with systemic lupus erythematosus (SLE) who developed fulminant multiorgan ischemic manifestations and hematologic abnormalities. She presented with persistent fever, newly developed painful fingertip cyanosis, and acute kidney injury. Laboratory tests showed severe thrombocytopenia, hemolytic anemia with fragmented red blood cells, positive direct and indirect Coombs tests, hypocomplementemia, and positivity for multiple autoantibodies, including a triple-positive antiphospholipid antibody profile. Within the first week of hospitalization, in addition to digital ischemia, she developed multiple cerebral infarctions and acalculous cholecystitis, findings consistent with catastrophic antiphospholipid syndrome (APS). Unexpectedly, the activity of a disintegrin and metalloproteinase with thrombospondin type 1 motifs member 13 (ADAMTS13) was severely reduced to 5%, whereas ADAMTS13 inhibitor was not detected by the Bethesda assay. There was no past medical or family history suggestive of congenital thrombotic thrombocytopenic purpura. After treatment with high-dose glucocorticoids and nine sessions of plasma exchange (PE), abdominal pain resolved and digital ischemia improved, accompanied by improvement in hematologic and renal abnormalities and disappearance of fragmented red blood cells. Subsequently, ADAMTS13 activity normalized to 63% and remained stable after completion of PE. Later, non-inhibitory anti-ADAMTS13 autoantibodies were detected by enzyme-linked immunosorbent assay in a stored serum sample obtained on admission. ADAMTS13 deficiency due to non-inhibitory anti-ADAMTS13 autoantibodies may modify the complications of SLE and APS by promoting thrombotic microangiopathy.

In the pediatric population, gastrointestinal (GIS) cancers are rare, and paraneoplastic syndromes associated with these malignancies are even more uncommon. A 15-year-old patient with a clinical presentation of microangiopathic hemolytic anemia (MAHA) resistant to plasma exchange was found to have metastatic adenocarcinoma in a biopsy of a supraclavicular lymphadenopathy. Subsequent endoscopy revealed gastric signet ring cell carcinoma. This case highlights that malignancy should be suspected in pediatric patients with MAHA who are unresponsive to plasma exchange and have normal ADAMTS-13 activity.

Autoimmune lymphoproliferative syndrome-like (ALPS-like) disorders are inherited conditions caused by non-FAS pathway mutations that clinically mimic ALPS, presenting with lymphoproliferation, autoimmunity, and cytopenias. This study describes a patient with STAT3-related ALPS-like disease that was initially misdiagnosed as ALPS and compares his clinical, immunological, and molecular features with those of previously reported cases to highlight diagnostic distinctions from classical ALPS. Clinical data were obtained from direct examination and medical records. Whole-Exome Sequencing (WES) identified the causative mutation. A literature review using PubMed, Web of Science, and Scopus retrieved previously reported ALPS-like cases with STAT3 mutations for comparative analysis of clinical, immunological, and molecular findings. We report a 10-year-old boy with bicytopenia (thrombocytopenia and neutropenia), autoimmune thrombocytopenic purpura, refractory lymphadenopathy, splenomegaly, and recurrent infections, initially misdiagnosed as ALPS. Elevated double-negative T cells and vitamin B12 levels were detected. WES revealed a heterozygous de novo STAT3 mutation (p.L666V). A reduced frequency of Treg cells was observed in our case. The patient responded well to JAK inhibitor therapy. Review of reported STAT3-mutant ALPS-like cases (66 cases) showed that immune thrombocytopenia was the most common cytopenia, often accompanied by autoimmune hemolytic anemia, variable hypogammaglobulinemia, reduced Treg cells, and increased double-negative T cells. STAT3 gain-of-function-associated ALPS-like disease can closely mimic classical ALPS due to overlapping clinical and immunological features, including elevated double-negative T cells, which may lead to diagnostic challenges. This case highlights that STAT3 GOF ALPS-like disease can closely mimic classical ALPS, and that integrating genetic analysis with immunological assessment is essential for accurate diagnosis and guiding targeted therapy.

ABSTRACTSnakebite envenomation remains a significant yet often overlooked health challenge in Nepal, particularly in its rural and hilly regions. While venom‐induced consumption coagulopathy (VICC) is commonly observed with viper bites, microangiopathic hemolytic anemia (MAHA) is an extremely rare complication, especially with green pit vipers (Trimeresurus spp.). MAHA is often underdiagnosed in low‐resource settings due to the absence of definitive laboratory diagnostics. We report a case of a 47‐year‐old woman from rural Nepal who was bitten by a presumed green pit viper (Trimeresurus spp.). She developed local swelling, ecchymosis, hematuria, anemia, thrombocytopenia, and coagulopathy. MAHA was diagnosed clinically based on syndromic presentation and serial hematologic monitoring, despite the unavailability of a peripheral blood smear. Due to species‐specific antivenom unavailability, the patient was treated with supportive care and blood product transfusions, and she achieved complete recovery without any renal complications. This case highlights the diagnostic challenges of MAHA in settings lacking definitive laboratory tests. It emphasizes the importance of clinical vigilance and syndromic diagnosis. Prompt, appropriate supportive management can lead to favorable outcomes even without antivenom availability. MAHA should be considered in snakebite victims presenting with thrombocytopenia and anemia. Strengthening diagnostic capacity and improving access to species‐specific antivenoms are critical for reducing morbidity and mortality from snakebite envenomation in resource‐limited settings.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common inherited enzymatic disorder, typically associated with hemolytic anemia. However, emerging evidence points to its involvement in a wider range of physiological processes, including the regulation of oxidative stress, immune defense, and epithelial repair which could lead to various manifestations. This is the first report of association between G6PD deficiency and perianal abscess and fistula. A 16-year-old male with a five-year history of recurrent perianal abscess and fistula presented with renewed symptoms despite prior surgical management. His mother and brother had also reportedly been diagnosed with perianal abscess and fistula. Laboratory findings showed anemia and elevated inflammatory markers, while imaging revealed an intersphincteric fistula tract. Colonoscopy exhibited focal active ileitis without granulomas. Whole-exome sequencing identified a hemizygous pathogenic/likely pathogenic mutation in the G6PD gene (c.653C > T), suggesting a genetic contribution to the chronic inflammatory process. This case highlights a possible association between G6PD deficiency and recurrent perianal abscess and fistula. Impaired immune response and epithelial repair linked to G6PD dysfunction may contribute to chronic perianal disease. Further studies are warranted to clarify this potential relationship.

To assess the incidence of associative immune-mediated haemolytic anaemia in dogs diagnosed with immune-mediated haemolytic anaemia and to evaluate whether performing diagnostic imaging, specifically thoracic radiographs and abdominal ultrasound, influences outcomes in non-associative immune-mediated haemolytic anaemia. Medical records (2017 to 2023) were reviewed for dogs diagnosed with immune-mediated haemolytic anaemia. Dogs were classified as associative immune-mediated haemolytic anaemia or non-associative immune-mediated haemolytic anaemia. Survival odds at 3, 6 and 12 months were assessed for non-associative immune-mediated haemolytic anaemia. Multivariable logistic regression was used to identify factors associated with a risk of decreased survival. Among 117 immune-mediated haemolytic anaemia cases, 7 (6%) had associative immune-mediated haemolytic anaemia, and 110 (94%) had non-associative immune-mediated haemolytic anaemia. In non-associative immune-mediated haemolytic anaemia dogs, thoracic radiographs were performed in 63 dogs (57.3%) and abdominal ultrasound in 90 dogs (81.8%), with unremarkable thoracic radiographs in 55.5% of cases and unremarkable abdominal ultrasound in 17.8%. Diagnostic imaging did not significantly affect the risk of decreased survival at 3, 6 and 12 months (P > .05). Increasing age (OR [95% CI]: 1.31 [1.06 to 1.61] at 12 months), elevated serum alanine aminotransferase (OR [95% CI]: 3.93 [1.11 to 14.0] at 3 months) and a higher number of packed red blood cell transfusions (OR [95% CI]: 2.10 [1.09 to 4.08] at 3 months and 1.91 [1.02 to 3.56] at 6 months) were associated with an increased risk of decreased survival. Performing diagnostic imaging was not associated with a change in survival odds in dogs with non-associative immune-mediated haemolytic anaemia in this cohort. These findings suggest individual case-based diagnostic imaging may be appropriate in clinical practice.

BACKGROUND Autoimmune hemolytic anemia (AIHA) is characterized by immune-mediated premature red blood cell destruction. Although AIHA has been reported after solid organ transplantation, it remains uncommon, and very late-onset presentations occurring decades after transplantation are rare. Both warm and cold AIHA have been reported after transplant. Reported etiologies include immune dysregulation, infections, post-transplant lymphoproliferative disorders, and medication-associated immune hemolysis, including calcineurin inhibitor-related effects. CASE REPORT A 30-year-old woman with orthotopic liver transplantation at age 9 for biliary atresia, on long-term tacrolimus, presented 21 years after transplant with exertional dyspnea and symptomatic anemia. Laboratory evaluation revealed severe anemia with biochemical evidence of hemolysis, including undetectable haptoglobin and reticulocytosis. A direct antiglobulin test was positive for IgG, confirming warm autoimmune hemolytic anemia. Antibody identification revealed a warm autoantibody, and crossmatch-compatible red blood cells were transfused without reaction. Extensive evaluation excluded gastrointestinal bleeding, infection including Epstein-Barr virus, post-transplant lymphoproliferative disorder, and thrombotic microangiopathy. She was treated with high-dose corticosteroids with partial response, followed by early rituximab due to persistent hemoglobin instability. The tacrolimus dose was modestly reduced but not discontinued. Bone marrow biopsy excluded hematolymphoid malignancy. The patient achieved complete remission with normalization of hemoglobin and hemolysis markers after 4 rituximab doses and steroid tapering. CONCLUSIONS Warm autoimmune hemolytic anemia can present decades after solid organ transplantation and should be considered in transplant recipients with unexplained anemia. Remission can be achieved with corticosteroids and early rituximab without discontinuation of tacrolimus. Further studies are needed to clarify optimal treatment strategies for late-onset post-transplant AIHA, including the role of early rituximab.

Fludarabine treatment in patients with chronic lymphocytic leukemia (CLL) has been associated with immune dysregulation and the development of autoimmune hemolytic anemia (AIHA). Prior research indicates a potential correlation between the expression of the SLC28A3gene, which encodes human concentrative nucleoside transporter 3 (responsible for fludarabine uptake), and treatment response. This retrospective study investigated the relationship between baseline SLC28A3expression levels, quantified via reverse-transcriptase polymerase chain reaction (qRT-PCR), and the incidence of AIHA in a cohort of CLL patients receiving fludarabine and cyclophosphamide (FC) therapy. Patients were categorized into two groups: "FC-emergent AIHA," encompassing patients who developed AIHA during or following FC therapy, and "no FC-emergent AIHA," which included patients with pre-existing AIHA prior to any treatment and those who remained AIHA-free throughout follow-up. A comparative analysis of these groups revealed no significant differences in most clinical and biological variables. However, a statistically significant difference was observed in median baseline SLC28A3expression, which was sevenfold lower in the "FC-emergent AIHA" group compared to the "no FC-emergent AIHA" group. Furthermore, SLC28A3 expression did not significantly correlate with most of the other clinical or biological parameters, including time to first treatment or overall survival. These findings suggest that diminished baseline SLC28A3expression may correlate with an elevated risk of fludarabine-emergent AIHAin CLL patients. Further validation through larger, prospective cohorts is essential to confirm the predictive utility of SLC28A3expression for optimizing fludarabine-based therapeutic strategies.

To investigate the clinical profile of nivolumab-induced autoimmune hemolytic anemia (AIHA) and to reveal the diagnostic and therapeutic patterns of this disease. Articles on nivolumab-induced AIHA published before October 31, 2025 were included. Clinical data were collected for retrospective analysis. A total of 29 patients were included, with a median age of 67 years (range: 18, 89). AIHA occurred at a median of 57 days (range: 6, 390) following initial nivolumab administration, with a median treatment cycle of 3 cycles (range: 1, 39). Fatigue (76.9%) and dyspnea (53.8%) were the predominant clinical manifestations. The laboratory analysis indicated that the median concentrations of hemoglobin and lactate dehydrogenase were 6.2g/dL (range: 3.5, 8.7) and 710.5U/L (range: 200, 1574), respectively. Direct antiglobulin test (DAT) results were seronegative in 10.3% and seropositive in 89.7%. Following nivolumab discontinuation and administration of systemic steroids, immunosuppressants, and transfusion support, 89.7% of patients achieved remission. AIHA is a rare and fatal event of nivolumab. DAT may yield negative results in some cases. Warm AIHA is the most common type of nivolumab-induced AIHA. Systemic steroids are the first-line option for AIHA. Refractory AIHA and cAIHA require additional immunosuppressive therapy.