Acquired Hemolytic Anemia in Children: A Comprehensive Review of Current Diagnostic and Therapeutic Approaches
1. Khan Kashish Haroon
2. Osmonova Gulnaz Zhenishbaevna
(1. Student, International Medical Faculty, Osh State University, Osh, Kyrgyz Republic
2. Teacher, International Medical Faculty, Osh State University, Osh, Kyrgyz Republic.)
Abstract
Acquired hemolytic anemia represents a heterogeneous group of disorders characterized by the premature destruction of erythrocytes following exposure to extrinsic factors, distinct from inherited hemoglobinopathies and membrane defects. In the pediatric population, these conditions encompass immune-mediated mechanisms, particularly autoimmune hemolytic anemia (AIHA), as well as non-immune causes including microangiopathic processes, infections, drug-induced hemolysis, and oxidative damage in glucose-6-phosphate dehydrogenase (G6PD) deficiency. This review examines the contemporary understanding of acquired hemolytic anemias in children, integrating recent advances in pathophysiology, diagnostic methodologies, and evidence-based therapeutic strategies. A comprehensive literature search was conducted focusing on publications from 2017 to 2025, with emphasis on pediatric-specific guidelines and emerging treatments. The analysis reveals that while corticosteroids remain the cornerstone of warm AIHA management, novel therapeutic approaches including complement inhibitors, B-cell targeted monoclonal antibodies, and precision immunosuppression are reshaping treatment paradigms. The prognosis varies considerably by etiology, with post-infectious AIHA generally demonstrating favorable outcomes, whereas secondary forms associated with primary immunodeficiencies or malignancies often require prolonged, multimodal therapy. Early recognition, accurate phenotypic characterization, and individualized treatment approaches are essential for optimizing outcomes in these potentially life-threatening conditions.
Introduction
The destruction of red blood cells constitutes a fundamental pathological process that, when accelerated beyond the compensatory capacity of bone marrow erythropoiesis, results in hemolytic anemia. While inherited disorders such as sickle cell disease and hereditary spherocytosis receive considerable attention in pediatric hematology, acquired forms of hemolytic anemia represent equally important clinical entities that demand distinct diagnostic and therapeutic approaches. These conditions arise when otherwise normal erythrocytes are subjected to extrinsic destructive forces, whether immune-mediated, mechanical, infectious, toxic, or oxidative in nature.
In children, acquired hemolytic anemias present unique diagnostic challenges. The clinical manifestations range from insidious fatigue and pallor to acute, life-threatening anemia with hemodynamic compromise. The heterogeneity of underlying etiologies—spanning from transient post-infectious immune dysregulation to chronic complement-mediated thrombotic microangiopathies—necessitates a systematic, mechanism-based approach to evaluation. Furthermore, the therapeutic landscape has evolved substantially in recent years, with the introduction of targeted biologic agents complementing traditional immunosuppressive strategies.
Autoimmune hemolytic anemia, the prototypical acquired hemolytic disorder of childhood, illustrates the complexity of this disease category. Characterized by autoantibody-mediated erythrocyte destruction with a positive direct antiglobulin test (DAT), AIHA affects children differently than adults, generally demonstrating more favorable responses to first-line therapy but requiring careful consideration of long-term immunosuppressive effects on developing immune systems. Recent epidemiological data indicate that AIHA remains rare in pediatrics, with a Korean single-center study identifying only 8 cases requiring therapeutic intervention among 475 children diagnosed with anemia over a twelve-year period, highlighting the importance of maintaining clinical vigilance despite low disease prevalence.
The classification of acquired hemolytic anemias has traditionally divided etiologies into immune and non-immune categories, with further subdivision based on the thermal characteristics of autoantibodies in AIHA (warm, cold, mixed, and paroxysmal cold hemoglobinuria) or the mechanism of erythrocyte injury in non-immune forms. This framework, while clinically useful, continues to evolve as molecular understanding deepens. The recognition of complement-mediated thrombotic microangiopathy as a distinct entity from thrombotic thrombocytopenic purpura, and the elucidation of genetic predispositions underlying apparently acquired conditions, have refined diagnostic algorithms and opened avenues for targeted intervention.
This review aims to provide a comprehensive examination of acquired hemolytic anemias in children, encompassing epidemiology, pathophysiological mechanisms, clinical presentation, diagnostic evaluation, and contemporary management strategies. Particular attention is directed toward recent advances in immunomodulatory therapy and the unique considerations applicable to the pediatric population.
Methods
A comprehensive literature search was conducted to identify relevant publications addressing acquired hemolytic anemias in pediatric populations. The search encompassed databases including PubMed, MEDLINE, and the Cochrane CENTRAL Trials Register, with primary focus on literature published between January 2017 and October 2025 to ensure inclusion of contemporary management guidelines and emerging therapeutic data. Search terms incorporated "acquired hemolytic anemia," "autoimmune hemolytic anemia," "pediatric," "children," "G6PD deficiency," "thrombotic microangiopathy," "hemolytic uremic syndrome," and "treatment guidelines."
Inclusion criteria prioritized original research articles, systematic reviews, meta-analyses, and clinical practice guidelines specifically addressing pediatric populations or containing substantial pediatric subgroups. The methodological framework emphasized evidence-based guidelines from hematological societies including the British Society for Haematology, the Italian Association of Pediatric Hematology-Oncology (AIEOP), and recent international consensus statements. Particular attention was directed toward studies characterizing treatment outcomes, novel therapeutic agents including complement inhibitors and monoclonal antibodies, and long-term follow-up data in pediatric cohorts.
The analysis synthesized data from multiple study designs, acknowledging the limitations inherent in the rare disease literature, where randomized controlled trials are scarce and therapeutic recommendations frequently derive from retrospective cohort studies, case series, and expert consensus. Reference was made to key epidemiological studies, including a 2024 scoping review of childhood AIHA that systematically evaluated evidence from 2000 to November 2023, and recent single-center retrospective analyses from international cohorts.
Results
Epidemiology and Classification
Acquired hemolytic anemias in children encompass several distinct clinical entities with varying incidence and age predilection. Autoimmune hemolytic anemia, while rare, represents the most frequently encountered immune-mediated acquired hemolytic disorder in pediatric practice. Epidemiological studies indicate that warm AIHA predominates in children, accounting for approximately 80% of cases, with cold antibody-mediated forms and paroxysmal cold hemoglobinuria comprising the remainder. A Brazilian retrospective study of 24 pediatric AIHA patients found that 83.3% presented with warm antibodies, with a median age at diagnosis of approximately 6 years and slight female predominance.
The incidence of AIHA demonstrates bimodal age distribution, with peaks in early childhood (under 5 years) and adolescence. Secondary AIHA, associated with underlying autoimmune conditions, immunodeficiencies, malignancies, or infections, occurs more frequently than primary idiopathic disease in pediatric series. Notably, a significant proportion of pediatric AIHA cases follow viral infections or vaccinations, suggesting immune dysregulation triggered by antigenic stimulation.
Non-immune acquired hemolytic anemias demonstrate distinct epidemiological patterns. G6PD deficiency, while genetically inherited, manifests as acquired hemolytic episodes following oxidative stress and affects more than 400 million people worldwide, with particularly high prevalence in Mediterranean, African, and Asian populations. Hemolytic uremic syndrome, predominantly caused by Shiga toxin-producing Escherichia coli (STEC), affects children under 5 years most commonly, with greater than 90% of typical HUS cases occurring in this age group.
Pathophysiological Mechanisms
The destruction of erythrocytes in acquired hemolytic anemias occurs through distinct mechanistic pathways that inform both classification and treatment. In warm AIHA, IgG autoantibodies bind erythrocyte surface antigens optimally at 37°C, targeting proteins such as band 3 and Rh antigens. These opsonized cells undergo extravascular hemolysis primarily in the spleen through Fcγ receptor-mediated phagocytosis by macrophages, though complement activation may augment destruction. The pathophysiology involves complex dysregulation of B-cell tolerance, T-cell helper function, and complement system activity, with recent evidence implicating alterations in regulatory T-cell populations and cytokine signaling.
Cold antibody-mediated hemolysis operates through distinct mechanisms. Cold agglutinin disease involves IgM autoantibodies, typically targeting I/i antigens, which bind erythrocytes at lower temperatures and fix complement, leading to intravascular hemolysis upon rewarming. Paroxysmal cold hemoglobinuria, characterized by the Donath-Landsteiner antibody (a biphasic IgG against the GLOB/P antigen), causes complement-mediated intravascular hemolysis following cold exposure.
Microangiopathic hemolytic anemias result from mechanical fragmentation of erythrocytes within the microvasculature. In thrombotic microangiopathies, deficient activity of ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 repeats, member 13) in TTP or complement dysregulation in atypical HUS leads to microthrombus formation, shearing erythrocytes and producing the characteristic schistocytes. Pneumococcal HUS involves neuraminidase-mediated exposure of cryptic antigens on erythrocytes, platelets, and glomerular endothelium, inducing widespread microvascular thrombosis.
Oxidative hemolysis in G6PD deficiency occurs when insufficient reduced glutathione renders erythrocytes vulnerable to oxidant injury. Exposure to fava beans, certain medications (including antimalarials, sulfonamides, and nitrofurantoin), or infections triggers hemoglobin denaturation, Heinz body formation, and splenic sequestration or intravascular destruction.
Clinical Presentation
The clinical manifestations of acquired hemolytic anemia in children vary dramatically in severity and tempo. Acute presentations feature pallor, fatigue, tachycardia, and jaundice, with dark urine indicating intravascular hemolysis. A Brazilian cohort study found that pallor affected 95.8% of children at presentation, with fatigue or lethargy in 79.1%, jaundice in 37.5%, and fever in 33.3%. Splenomegaly was detected in approximately one-third of patients.
Severe anemia may precipitate high-output cardiac failure, particularly in infants and young children with limited cardiovascular reserve. Neurological symptoms, including irritability, headache, and altered consciousness, may accompany severe anemia or microvascular thrombosis in thrombotic microangiopathies. The classic pentad of TTP—thrombocytopenia, microangiopathic hemolytic anemia, neurological abnormalities, renal dysfunction, and fever—though historically emphasized, is frequently incomplete in pediatric presentations.
Cold antibody-mediated hemolysis presents with characteristic features including acrocyanosis, livedo reticularis, and hemoglobinuria following cold exposure. Paroxysmal cold hemoglobinuria, typically occurring in young children following viral infections, manifests as sudden, dramatic hemoglobinuria with pallor and jaundice upon cold exposure, often with associated abdominal pain and fever.
The clinical context provides essential diagnostic clues. Recent diarrheal illness preceding hemolytic anemia with thrombocytopenia and renal involvement suggests STEC-HUS. Upper respiratory infections, particularly Mycoplasma pneumoniae, precede cold agglutinin formation. Drug exposure history is critical for identifying drug-induced hemolysis, whether immune-mediated or oxidative in G6PD-deficient patients.
Diagnostic Evaluation
The diagnostic approach to acquired hemolytic anemia requires systematic laboratory evaluation to confirm hemolysis, characterize its mechanism, and identify underlying etiologies. Initial assessment includes complete blood count demonstrating anemia with reticulocytosis (though reticulocyte response may be inadequate in acute presentations or with concurrent bone marrow suppression), elevated lactate dehydrogenase, indirect hyperbilirubinemia, and decreased haptoglobin. Peripheral blood smear examination provides crucial morphological evidence: spherocytes suggest warm AIHA or hereditary spherocytosis, schistocytes indicate microangiopathic processes, and Heinz bodies (with crystal violet staining) point to oxidative damage.
The direct antiglobulin test (DAT, or Coombs test) remains central to diagnosing immune-mediated hemolysis. Current guidelines recommend monospecific anti-IgG and anti-C3d reagents to characterize antibody class and complement fixation. DAT-positive hemolysis with IgG alone typically indicates warm AIHA, while isolated C3d positivity suggests cold antibody-mediated disease or paroxysmal cold hemoglobinuria. However, DAT-negative AIHA occurs in 3-11% of cases, necessitating repeat testing with column agglutination methods including anti-IgA and anti-C3d, or red cell eluate preparation when clinical suspicion remains high.
Further serological evaluation includes indirect antiglobulin testing to identify alloantibodies in recently transfused patients, and cold agglutinin titers with thermal amplitude testing for cold antibody disease. The Donath-Landsteiner test, utilizing biphasic incubation at 0°C and 37°C with complement, confirms paroxysmal cold hemoglobinuria.
For microangiopathic hemolytic anemias, urgent ADAMTS13 activity measurement distinguishes TTP (severe deficiency, typically <10%) from complement-mediated TMA and STEC-HUS. Shiga toxin testing in stool and complement genetic studies for atypical HUS guide specific therapies. G6PD enzyme assay requires careful timing—testing during acute hemolysis may yield falsely normal results due to reticulocyte enrichment, necessitating repeat testing after recovery.
Bone marrow examination is generally reserved for cases with atypical features, concurrent cytopenias suggesting marrow infiltration or failure, or before initiating immunosuppressive therapy. Evaluation for underlying conditions includes antinuclear antibodies and anti-double-stranded DNA for systemic lupus erythematosus, immunoglobulin levels and lymphocyte subsets for primary immunodeficiencies, and viral serologies for Epstein-Barr virus, cytomegalovirus, and parvovirus B19.
Treatment Approaches
Autoimmune Hemolytic Anemia
Corticosteroids remain the cornerstone of first-line therapy for warm AIHA in children. Current guidelines recommend prednisolone at 1-2 mg/kg/day, with some pediatric protocols favoring the higher end of this range (2 mg/kg/day) given children's generally favorable risk-benefit profile for short-term corticosteroid use. Intravenous methylprednisolone (7-8 mg/kg/day or 30 mg/kg/day for 3 days in severe cases) is preferred for patients with severe anemia, high fever, or inability to tolerate oral intake. Response typically occurs within two weeks, with hemoglobin normalization expected by two to four weeks in responsive cases. The Korean cohort study demonstrated complete response in all eight treated patients, with median time to normal hemoglobin of 16.5 days and median steroid duration of only 37.5 days—substantially shorter than typical adult treatment courses.
Tapering should be gradual, extending over at least 2-6 months to prevent relapse, though pediatric patients often tolerate more rapid discontinuation than adults. All patients require folic acid supplementation to support increased erythropoiesis, and calcium/vitamin D supplementation during corticosteroid therapy.
Intravenous immunoglobulin (IVIg) serves as adjunctive therapy in severe cases, particularly with hemoglobin below 6-7 g/dL, though its efficacy remains debated. The mechanism involves Fc receptor blockade and modulation of autoantibody production. Plasma exchange provides temporary control in life-threatening hemolysis by removing autoantibodies and complement components.
Second-line therapy is indicated for steroid non-response after three weeks, relapse during taper, or steroid intolerance. Rituximab, a chimeric anti-CD20 monoclonal antibody depleting B lymphocytes, has emerged as the preferred second-line agent. The standard pediatric dosing (375 mg/m² weekly for four weeks) achieves response rates of approximately 80% with median recovery times of 6-7 weeks. Concerns regarding long-term B-cell depletion, hypogammaglobulinemia, and rare complications including progressive multifocal leukoencephalopathy must be weighed against benefits, particularly in young children.
For steroid-dependent patients requiring maintenance therapy, mycophenolate mofetil has become the preferred steroid-sparing agent, demonstrating favorable safety profiles in pediatric populations. Other immunosuppressants including azathioprine, cyclosporine, and sirolimus serve as third-line options, with sirolimus showing particular promise in refractory warm AIHA and Evans syndrome.
Splenectomy, historically a mainstay of second-line therapy, is now generally deferred in children due to the lifelong risk of overwhelming post-splenectomy sepsis, particularly in those under 5 years. It remains considered for older children with refractory disease following rituximab failure, after appropriate vaccinations and antibiotic prophylaxis.
Cold antibody-mediated AIHA requires distinct approaches. Thermal protection—avoiding cold exposure and warming transfused blood—is fundamental. Rituximab is first-line for cold agglutinin disease, while corticosteroids are generally ineffective. Complement inhibitors including eculizumab and sutimlimab show increasing promise, particularly for CAD and mixed AIHA, by blocking C5-mediated intravascular hemolysis. Paroxysmal cold hemoglobinuria in children is typically self-limited, requiring only supportive care and transfusion when necessary, though severe cases have responded to plasma exchange, rituximab, and complement inhibition.
Thrombotic Microangiopathies
The management of pediatric thrombotic microangiopathy has been transformed by etiology-specific approaches. STEC-HUS remains primarily supportive, with careful fluid management, blood pressure control, and renal replacement therapy when indicated. Critically, antibiotics are contraindicated in suspected STEC infection as they may increase Shiga toxin release and HUS risk.
Complement-mediated TMA (atypical HUS) requires urgent eculizumab, a monoclonal antibody against C5 that prevents formation of the membrane attack complex. This therapy has dramatically improved outcomes, converting a previously fatal or end-stage renal disease-causing condition to a manageable chronic disease. Lifelong treatment is typically required, with meningococcal vaccination essential before initiation.
TTP, whether congenital (ADAMTS13 mutations) or immune-mediated (autoantibodies), requires plasma-based therapy. Plasma exchange removes autoantibodies and provides functional ADAMTS13 in acquired TTP, while plasma infusion alone suffices for congenital TTP due to the need for continuous enzyme replacement. Corticosteroids and rituximab treat the underlying autoimmunity in acquired TTP.
Oxidative and Drug-Induced Hemolysis
G6PD deficiency management centers on trigger avoidance and supportive care during acute episodes. Transfusion is reserved for severe anemia (hemoglobin <5 g/dL or <7 g/dL with cardiac decompensation), using 3-5 mL/kg of packed red cells over 4 hours. The deficient enzyme cannot be corrected, making prevention through patient education regarding oxidant drugs (including certain antimalarials, sulfonamides, nitrofurantoin, and rasburicase) and fava beans paramount. Neonatal screening programs are increasingly implemented in high-prevalence regions.
Drug-induced immune hemolytic anemia requires immediate discontinuation of the offending agent, with transfusion support for severe cases. The mechanism may involve drug-dependent antibodies (requiring the drug for antibody binding) or drug-independent autoantibodies that persist after drug discontinuation.
Prognosis and Long-term Outcomes
The prognosis of acquired hemolytic anemia in children varies substantially by etiology and treatment response. Post-infectious AIHA generally carries excellent prognosis, with most children achieving complete recovery within weeks to months. The Brazilian cohort demonstrated that over half of patients were discharged as cured, with no deaths during median follow-up of 4.4 years.
However, certain subgroups face more guarded outcomes. Secondary AIHA associated with primary immunodeficiencies, autoimmune lymphoproliferative syndrome, or malignancies often follows a chronic, relapsing course requiring prolonged immunosuppression. Evans syndrome (AIHA with immune thrombocytopenia) frequently indicates underlying immune dysregulation and may precede diagnosis of conditions such as common variable immunodeficiency or autoimmune lymphoproliferative syndrome.
Long-term complications of therapy require consideration. Chronic corticosteroid exposure affects growth, bone density, and metabolic parameters in children. Rituximab-induced hypogammaglobulinemia may persist for years, necessitating immunoglobulin replacement in some patients. Splenectomy, when performed, mandates lifelong infection prophylaxis protocols.
Discussion
The management of acquired hemolytic anemia in children has evolved substantially, shifting from empiric corticosteroid-based approaches toward mechanism-informed, targeted therapies. This evolution reflects broader advances in understanding immune dysregulation, complement biology, and the genetic underpinnings of apparently acquired conditions.
The pediatric AIHA landscape illustrates both progress and persistent challenges. While children generally demonstrate superior responses to corticosteroids compared to adults—often achieving complete remission with shorter treatment courses—the absence of randomized controlled trials leaves significant uncertainty regarding optimal dosing, tapering schedules, and second-line sequencing. The 2024 scoping review by Zhang et al. highlighted this evidence gap, identifying no randomized trials in pediatric AIHA and substantial variability in diagnostic criteria and treatment approaches across studies. This variability reflects the rarity of the condition and the ethical complexities of clinical trials in serious pediatric illnesses, but underscores the need for international collaborative registries to generate robust evidence.
The emergence of complement inhibition represents a paradigm shift for cold antibody-mediated hemolysis and thrombotic microangiopathies. Eculizumab's success in atypical HUS has been particularly dramatic, transforming outcomes for a previously devastating condition. Sutimlimab, targeting C1s in the classical complement pathway, offers more specific inhibition for cold agglutinin disease without conferring the meningococcal risk associated with C5 inhibition. These agents raise important questions regarding long-term use in growing children, including vaccination strategies, breakthrough hemolysis, and pharmacoeconomic considerations.
The recognition of genetic predispositions underlying many "acquired" hemolytic anemias blurs traditional classification boundaries. Atypical HUS frequently reveals complement gene mutations or autoantibodies against factor H, suggesting these represent manifestations of underlying complement dysregulation triggered by environmental factors. Similarly, AIHA occurring in the context of primary immunodeficiencies or immune dysregulation syndromes reflects genetically determined failure of immune tolerance. This molecular understanding enables more precise prognostication and, potentially, curative approaches such as hematopoietic stem cell transplantation for severe refractory cases associated with primary immunodeficiency.
The role of splenectomy has diminished considerably in pediatric practice, reflecting increased availability of effective medical alternatives and heightened awareness of long-term infectious risks. However, it retains utility in carefully selected older children with refractory warm AIHA, particularly those with IgG-mediated disease without underlying immunodeficiency. The timing of splenectomy relative to rituximab exposure requires careful consideration, as splenectomy after rituximab may carry heightened infectious risk due to combined B-cell depletion and asplenia.
Supportive care elements remain crucial across all acquired hemolytic anemias. Transfusion strategies require careful attention to compatibility testing, as autoantibodies may complicate crossmatching. The concept of "least incompatible" blood—selecting units with the fewest serological incompatibilities when complete matching is impossible—has replaced historical reluctance to transfuse AIHA patients. For cold antibody disease, blood warming prevents exacerbation of hemolysis during transfusion. Folic acid supplementation supports the increased erythropoietic demand in chronic hemolysis, while monitoring for iron overload in chronically transfused patients prevents secondary complications.
Future directions in pediatric acquired hemolytic anemia include the development of more targeted B-cell therapies preserving protective immunity, such as selective depletion of autoreactive B-cell subsets or modulation of B-cell activating factor signaling. Fcγ receptor blockade using agents like nipocalimab offers promise for IgG-mediated hemolysis without generalized immunosuppression. Proteasome inhibitors and Bruton tyrosine kinase inhibitors, currently under investigation in adult refractory AIHA, may extend to pediatric applications. Most fundamentally, improved understanding of the triggers converting transient immune dysregulation into sustained autoimmunity may enable preventive interventions for post-infectious AIHA.
Conclusion
Acquired hemolytic anemias in children encompass a diverse spectrum of disorders unified by extrinsic erythrocyte destruction. While sharing common hematological features of hemolysis, these conditions require distinct diagnostic approaches and etiology-specific management. Warm AIHA remains the predominant immune-mediated form, generally responding favorably to corticosteroids, though rituximab and other targeted agents have expanded options for refractory cases. Non-immune forms, particularly thrombotic microangiopathies and oxidative hemolysis, demand urgent recognition and specific interventions—eculizumab for complement-mediated TMA and trigger avoidance for G6PD deficiency.
The prognosis for children with acquired hemolytic anemia has improved considerably with advances in supportive care and targeted therapy, though challenges persist in secondary forms associated with immune dysregulation or malignancy. Multidisciplinary collaboration between pediatric hematologists, nephrologists, immunologists, and transfusion medicine specialists optimizes outcomes for these complex patients. Future research priorities include prospective trials to establish evidence-based treatment algorithms, elucidation of genetic and environmental interactions triggering autoimmunity, and development of curative approaches for refractory disease. Through continued advances in mechanistic understanding and therapeutic innovation, the outlook for children with these challenging disorders continues to brighten.
References
Hill QA, Stamps R, Massey E, Grainger JD, Provan D, Hill A, British Society for Haematology. The diagnosis and management of primary autoimmune haemolytic anaemia. Br J Haematol. 2017;176(3):395-411.
Ladogana S, Maruzzi M, Samperi P, Perrotta S, Del Vecchio GC, Notarangelo LD, et al. Diagnosis and management of newly diagnosed childhood autoimmune haemolytic anaemia. Recommendations from the Red Cell Study Group of the Paediatric Haemato-Oncology Italian Association. Blood Transfus. 2017;15(3):259-267.
Zhang C, et al. Childhood autoimmune hemolytic anemia: A scoping review. Eur J Haematol. 2024;112(5):421-435.
Chandra D, et al. Autoimmune hemolytic anemia in children. Pediatr Hematol Oncol J. 2024;9(2):45-53.
Loriamini M, Cserti-Gazdewich C, Branch DR. Autoimmune Hemolytic Anemias: Classifications, Pathophysiology, Diagnoses, and Management. Int J Mol Sci. 2024;25(8):4296.
Kim Y, et al. Treatment and clinical outcomes of pediatric autoimmune hemolytic anemia: real-world single-center data from Korea. Clin Exp Pediatr. 2025;68(4):185-193.
de Albuquerque Rocha N, et al. Pediatric autoimmune hemolytic anemia: A single-center retrospective study. Hematol Transfus Cell Ther. 2024;46(4):345-352.
Egyptian Ministry of Health. Diagnosis, Management and Prevention of Acute Hemolytic Anemia in Infants, Children and Adolescents: Adapted Clinical Practice Guidelines. Egypt J Pediatr. 2023;45(Suppl 1):1-45.
Frank JE. Diagnosis and management of G6PD deficiency. Am Fam Physician. 2005;72(7):1277-1282.
British Society for Haematology. Laboratory diagnosis of glucose-6-phosphate dehydrogenase deficiency. Br J Haematol. 2020;189(1):24-38.
Azoulay E, et al. HUS and TTP: traversing the disease and the age spectrum. Blood. 2023;142(12):1023-1034.
Palomo M, et al. Thrombotic microangiopathy in children. Pediatr Hematol Oncol J. 2024;9(1):12-20.
Michel M, et al. Intravenous immunoglobulin as a rescue therapy for severe adult autoimmune hemolytic anemia: results from a French multicenter observational study. Am J Hematol. 2024;99(12):1616-1619.
Barcellini W, Zaninoni A, Giannotta JA, Fattizzo B. New insights in autoimmune hemolytic anemia: from pathogenesis to therapy. J Clin Med. 2020;9(12):3859.
Berrueco R, Gonzalez-Forster E, Deya-Martinez A. Mycophenolate mofetil for autoimmune cytopenias in children: High rates of response in inborn errors of immunity. Front Pediatr. 2023;11:1174671.