Autoimmune Hemolytic Anemia Research Articles

Parsaclisib for the treatment of primary autoimmune hemolytic anemia: Results from a phase 2, open-label study.

Autoimmune hemolytic anemia (AIHA) is a group of acquired autoimmune disorders characterized by red blood cell hemolysis. In a phase 2, open-label, multicenter study, adults with warm AIHA, cold agglutinin disease, or mixed-type AIHA were administered once-daily 1.0 or 2.5 mg parsaclisib (selective phosphoinositide 3-kinase δ inhibitor) orally for 12 weeks, followed by an extension period. Dose increases (for AIHA worsening) or decreases (for tolerability) were permitted. Primary efficacy endpoint was the proportion of patients with complete (≥12 g/dL hemoglobin [Hgb]) or partial (10-12 g/dL Hgb or ≥2 g/dL increase from baseline) response at any visit during weeks 6-12 not attributable to transfusion. Among 25 enrolled patients (median age, 63 y), 16 (64%) achieved a partial or complete Hgb response during weeks 6-12. Responses were observed by week 1 in 52.0% of patients with incremental improvements during weeks 6-12 and sustained responses during the extension period. Responses were higher among patients with warm AIHA versus other types (75.0% vs. 44.4%). Clinically meaningful improvements in Functional Assessment of Chronic Illness Therapy-Fatigue scores were observed at weeks 6 and 12. All patients had treatment-emergent adverse events (TEAEs), most commonly diarrhea (32.0%) and pyrexia (28.0%). Grade ≥3 TEAEs occurred in 13 patients (52.0%). TEAEs considered possibly related to treatment occurred in 11 patients (44.0%). No dose reductions were required; six patients (24%) discontinued for a TEAE. In summary, parsaclisib was well tolerated and resulted in substantial improvements in Hgb response at week 1, with durable responses through the extension period. CLINICAL TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov (NCT03538041).

ANA-positive versus ANA-negative Antiphospholipid Antibody-positive Patients: Results from the APS ACTION Clinical Database and Repository.

This study focused on the prevalence and impact of antinuclear antibodies (ANA) in antiphospholipid antibody (aPL)-positive patients without concomitant systemic autoimmune rheumatic diseases (SARDs). Data from aPL-positive patients with or without Revised Sapporo APS classification criteria were retrieved from the APS ACTION Registry. Patients with concomitant SARDs were excluded. 430 aPL-positive patients were included in the analysis, 56% ANA-positive and 44% negative. ANA positivity was significantly associated with history of hematologic manifestations (persistent autoimmune hemolytic anaemia, thrombocytopenia, leukopenia and/or lymphopenia) (16% of ANA-positive vs 7% of ANA-negative, p= 0.006). Triple aPL-positivity was more frequent in the ANA-positive subgroup (p= 0.02), along with low baseline C3 and C4 levels (p= 0.05 and p= 0.009, respectively), and higher frequency for extractable nuclear antigens (ENA). Among aPL-positive patients with no APS classification, ANA-positive patients showed a higher rate of arthritis (p= 0.006). Among female patients who have experienced at least one pregnancy, 113 were ANA-positive and 96 were ANA-negative; ANA-negative patients had a higher number of pregnancies (p= 0.018), and number of live births (p= 0.014). A wider proportion of ANA-positive patients were treated with hydroxychloroquine (HCQ) (p< 0.001). When we analysed aPL-positive patients with no other SARDs, ANA status was not associated with thrombosis or pregnancy morbidity. Interestingly, ANA-positive patients showed higher rates of systemic autoimmune features, including hematologic manifestations, multiple aPL positivity, lower complement levels, ENA positivity, and joint involvement, and were more often treated with HCQ. Finally, aPL-positive subjects who were ANA-negative had a higher rate of pregnancies and live births.

Correlation Crossmatching Test with Effectiveness of Transfusion in Hemolytic Anemia Patients

Hemolytic anemia is anemia caused by the premature destruction of red blood cells. Transfusion with hemolytic anemia is a dilemmatic indication and is still based on clinical decisions. Several studies assessed the effectiveness of transfusions in hemolytic anemia patients with incompatible crossmatching showed effectiveness. This study aimed to analyze crossmatching with transfusion effectiveness in hemolytic anemia patients. Retrospective cohort observational study with medical record data from January 2019 to May 2022 of hemolytic anemia patients who got transfusion therapy. The variables included age, gender, hemoglobin levels before and after transfusion, crossmatching test, and transfusion effectiveness based on increased hemoglobin after transfusion 1 g/dL of 1 Pack Red Cell (PRC) unit. One hundred three (103) patients with hemolytic anemia 45 received PRC, 12 males (26.7%) and 33 females (73.3%). Ages 19 - &lt; 45 years subjects had the most transfusions. Hemoglobin levels before and after transfusion showed significant differences (p-value =0.000) in the patients with a diagnosis of hereditary, unspecified, and autoimmune hemolytic anemias. The correlation between the effectiveness of transfusions with gender and age was not found (p=0.521, p=0.240). The correlation between crossmatching with the effectiveness of transfusion was not found (p=0.089). Hemolytic anemia patients with transfusion showed an increase in hemoglobin levels between before and after transfusion even with incompatible crossmatching. The correlation between the results of crossmatching with transfusion effectiveness in patients with hemolytic anemia was not found. Good premedication treatment can provide effective transfusion.

Molecular testing in a patient with multiple alloantibodies and warm autoimmune hemolytic anemia: A case study

Abstract Introduction/Objective We present a case of RBC alloimmunization and warm autoimmune hemolytic anemia (WAIHA) in a patient with a recent RBC transfusion. Serological testing followed by molecular testing revealed a rare D+ C- E- partial c+ partial e+ VS+ V+ hrS+ hrB+vw/- predicted phenotype. Methods/Case Report A 75-year-old black male with secondary myelofibrosis presented with a sudden onset of chest pain, dyspnea and weakness during an RBC transfusion. The patient was subsequently admitted for further workup. Labs showed low hemoglobin, low haptoglobin, elevated LDH and a positive direct antiglobulin (DAT) test. The patient was started on intravenous immunoglobulin and steroids for suspected WAIHA. On immunohematology serologic testing, blood typed as B-positive and polyspecific DAT positive with anti-IgG positive and anti-C3 negative. Serum plasma studies showed probable warm autoimmune hemolytic anemia and allo anti-S, -E, and -C by previous history. Eluate studies showed panagglutinin and antibody with D-like specificity. Immucor PreciseTypeTM Human Erythrocyte Antigen (HEA) Molecular BeadChip test predicted a partial e antigen and potential hrB-. Genotyping for RHD variants was performed and revealed RHD*01 (homozygous or hemizygous). Targeted genomic testing did not detect variants associated with common partial or weak RhD antigens. Based on this testing, the patient was not predicted to be at risk of allo-anti-D. An RHCE genotype for C, c, E and e variants including hrB and hrS showed RHCE*ce48C,733G/RHCE*ce733G with predicated phenotype of D+ C- E- partial c+ partial e+ VS+ V+ hrS+ hrB+vw/-. Based on the RHCE testing, the patient was predicted to be at risk for allo-anti-c, -e, -f (ce) and possibly anti-hrB. Results (if a Case Study enter NA) NA Conclusion In this case, serologic testing alone did not reveal a precise diagnosis. Molecular testing aided in the diagnosis of WAIHA and will help guide future transfusions. Pathologists must consider molecular testing when faced with a challenging serologic diagnosis.

Case Report: Acute hepatitis A virus infection presenting with direct antiglobulin test-negative autoimmune hemolytic anemia and α-thalassemia trait

Reports from the literature have discussed patients presenting Hepatitis A virus infection with hemolytic anemia, specifically with glucose-6-phosphate dehydrogenase deficiency. However, autoimmune hemolytic anemia (AIHA) has been rarely reported. We present a challenging case of Coombs-negative hemolytic anemia as initial manifestation of hepatitis A virus infection in a silent carrier of α-thalassemia.

Overall Survival and Treatment Patterns Among Patients With Warm Autoimmune Hemolytic Anemia in Sweden: A Nationwide Population-based Study.

Warm autoimmune hemolytic anemia (wAIHA) is a rare autoantibody-mediated disorder, and first-line treatment primarily relies on corticosteroids. This study assessed overall survival (OS) and treatment patterns of wAIHA in Sweden. Adults with ≥ 1 primary diagnosis code for wAIHA (or AIHA plus oral corticosteroids (OCS)/immunosuppressants as sensitivity analyses) between 2011 and 2022 were identified from five Swedish national registers and linked through each patient's unique identity number. Kaplan-Meier curves with log-rank tests and Cox regressions were performed to assess OS for patients with primary versus secondary wAIHA and patients with wAIHA and long-term versus short-term (≥ 3 vs. < 3 months) OCS users. The main analysis included 292 patients; 1791 patients were included in the sensitivity analysis. At a median 3.7-year follow-up, a median OS in primary wAIHA was not reached versus 6.0 years for secondary wAIHA (log-rank test: p = 0.003). Subgroup analyses showed no significant difference in risk of death between long-term and short-term OCS users; however, in the sensitivity analysis, long-term OCS users showed significantly higher risk of death (adjusted hazard ratio: 1.45; 95% confidence interval: 1.180, 1.781; p < 0.001) versus short-term OCS users. Secondary wAIHA or long-term OCS use was associated with lower OS, underscoring the disease burden and unmet need for efficacious wAIHA treatments.

Managing macrophage activation syndrome SLE: Clinical and therapeutic insights

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with frequent hematologic complications, including leukopenia, thrombocytopenia, autoimmune hemolytic anemia, and, in rare cases, macrophage activation syndrome (MAS). MAS, a severe hyperinflammatory condition, presents diagnostic challenges due to its overlap with SLE flares, infections, and drug-related adverse effects. This case report presents a 22-year-old female with SLE who experienced clinical deterioration following methotrexate initiation, manifesting as fever, pancytopenia, and transaminitis. Differential diagnoses were considered, including MAS, infection, and methotrexate toxicity. Prompt recognition and management with corticosteroids and immunoglobulins led to clinical improvement, underscoring the complexity of diagnosing and treating MAS in SLE patients.

Cold autoantibody interference in pretransfusion testing and its resolution: a case report

We report a case of cold autoantibody detected in a 69-year-old gentleman diagnosed with chronic lymphocytic leukemia and cold autoimmune hemolytic anaemia. Pretransfusion testing showed panagglutination in ABO grouping, antibody screening and identification, with positive direct antiglobulin test (DAT) and positive control cells. A cold autoantibody was suspected, however, the test using a prewarm method and washed RBC with warm saline failed to resolve it. Further tests using DTT-treated cells resolved the grouping as AB RhD positive and DAT as positive with anti-C3d only (control negative). Cold autoadsorption was done and repeated antibody screening using cold-autoadsorped plasma was negative, excluding the presence of alloantibody. The cold-agglutinin titer was &gt;1028 having a wide thermal range. Crossmatching using cold autoadsorped plasma with the AB-positive donor blood was compatible and the patient was transfused safely. For such cold autoantibody cases, an extensive immunohematological workup is required to exclude underlying alloantibody for transfusion safety and efficacy. Bangladesh Journal of Medical Science Vol. 23 No. 04 October’24 Page : 1238-1242

Acute autoimmune hemolytic anemia in a patient with systemic lupus erythematosus

Introduction Autoimmune hemolytic anemia occurs due to the accelerated destruction of erythrocytes as a result of the dysfunction of immune system cells, which produce antibodies against the normal antigens of the membrane of hematopoietic cells. One of its causes is systemic lupus erythematosus. Materials and methods We present a case of a 20-year-old patient who was hospitalized with acute autoimmune hemolytic anemia, having been diagnosed with SLE at the age of 18 years. At the onset of the disease, hemolytic anemia was a differential diagnostic challenge. Results The differential diagnosis between primary and secondary autoimmune hemolytic anemia (AIHA) was an important step. The presence of antinuclear antibodies (ANA Hep2, Anti-dsDNA, Anti-cardiolipin, Anti-phospholipids, anti-Ro, Anti-Sm B) were important arguments in making the diagnosis. The relapse of AIHA was caused by inadequate treatment, due to a lack of compliance. Pulse therapy combined with methylprednisolone and cyclophosphamide successfully resolved the AIHA. Conclusions Hematological abnormalities are commonly seen in SLE patients, but hemolytic autoimmune anemia is a rare condition. A timely diagnosis of the cause of hemolytic anemia and proper treatment of lupus by correcting autoimmune disorders are crucial in disease management. Pulse therapy combined with corticosteroids and immunosuppressants is effective in acute relapses of hemolytic anemia.

Factors predictive of severe thrombocytopenia and its impact on poor outcomes in Latin American patients with systemic lupus erythematosus: Data from a multiethnic Latin American cohort

ObjectiveTo examine the predictors of the occurrence of severe thrombocytopenia and its impact on damage accrual and mortality in SLE patients. MethodsFactors associated with time to severe thrombocytopenia (platelet count ≤20,000/mm3) occurring from the onset of SLE symptoms were assessed by Cox proportional hazards regressions. The association of severe thrombocytopenia with mortality was evaluated by logistic regression analyses while its impact on damage was by negative binomial regression. ResultsOf 1,217 patients, 33 (2.7%) developed severe thrombocytopenia over a mean (SD) follow-up time of 5.9 (3.6) years. The median time from the onset of SLE symptoms to severe thrombocytopenia occurrence was 22 months (IQR 8.7–62.0). Mestizo (60.6%) was the predominant ethnic group, followed by Caucasian (27.3%), while African Latin American exhibited the lowest frequency (12.1%). By multivariable analysis, Mestizo ethnicity (HR 2.67, 95% CI 1.12–6.37, p = 0.027), and autoimmune hemolytic anemia (AIHA) at baseline (HR 3.99; 95% CI 1.05–15.19, p = 0.042) were associated with a shorter time to the occurrence of severe thrombocytopenia while middle/high socioeconomic status (HR 0.23; 95% CI 0.08–0.69, p = 0.008) was associated with a longer time. Severe thrombocytopenia contributed neither to damage nor to mortality. ConclusionsSevere thrombocytopenia occurs during the early course of SLE. Mestizo ethnicity and AIHA at baseline emerged as independent predictors of a shorter time to severe thrombocytopenia occurrence while a middle/high socioeconomic status seems to be protective against its occurrence. Damage and mortality did not seem to be impacted by the occurrence of severe thrombocytopenia.

Potent efficacy of an IgG-specific endoglycosidase against IgG-mediated pathologies.

Endo-β-N-acetylglucosaminidases (ENGases) that specifically hydrolyze the Asn297-linked glycan on immunoglobulin G (IgG) antibodies, the major molecular determinant of fragment crystallizable (Fc) γ receptor (FcγR) binding, are exceedingly rare. All previously characterized IgG-specific ENGases are multi-domain proteins secreted as an immune evasion strategy by Streptococcus pyogenes strains. Here, using in silico analysis and mass spectrometry techniques, we identified a family of single-domain ENGases secreted by pathogenic corynebacterial species that exhibit strict specificity for IgG antibodies. By X-ray crystallographic and surface plasmon resonance analyses, we found that the most catalytically efficient IgG-specific ENGase family member recognizes both protein and glycan components of IgG. Employing invivo models, we demonstrated the remarkable efficacy of this IgG-specific ENGase in mitigating numerous pathologies that rely on FcγR-mediated effector functions, including T and B lymphocyte depletion, autoimmune hemolytic anemia, and antibody-dependent enhancement of dengue disease, revealing its potential for treating and/or preventing a wide range of IgG-mediated diseases in humans.

Association of paediatric autoimmune cytopenia and inflammatory bowel disease suggests a common genetic origin.

The association of autoimmune cytopenia (AIC) and inflammatory bowel disease (IBD) has been reported in small series, but the incidence of and risk factors for IBD in children with AIC are not known. One thousand six hundred nine children with chronic immune thrombocytopenic purpura, autoimmune haemolytic anaemia or Evans syndrome from the prospective OBS'CEREVANCE cohort are included in this study. Overall, 15 children were diagnosed with IBD, including 14 who developed IBD after AIC diagnosis (median delay: 21 months). The only risk factor for IBD development is age at AIC over 10 years. Out of 10 children genetically tested, germline variants associated with autoimmune disorders were identified in three (CTLA4: two, DOCK11: one). In children and adolescents monitored for AIC or past history of AIC, especially children over 10 years, gastro-intestinal (GI) symptoms (recurrent abdominal pains, GI bleeding, chronic diarrhoea, weight loss) should suggest IBD and deserve specific work-up and genetic studies. Identification of a causal germline variant will allow targeted therapy.

S3840 Autoimmune Hemolytic Anemia as an Extraintestinal Manifestation of Inflammatory Bowel Disease

S3840 Autoimmune Hemolytic Anemia as an Extraintestinal Manifestation of Inflammatory Bowel Disease

Anemia hemolítica en la infancia secundaria a neumonía por Mycoplasma pneumoniae

Autoimmune hemolytic anemia is rare in childhood with an incidence of approximately 0.8-1.25 cases per 100,000 children and is the most frequent cause of extracorpuscular hemolytic anemia, having a higher incidence between 3 and 4 years of age. Most of them are idiopathic, although they can also be secondary to autoimmune diseases, lymphoproliferative syndromes, tumors or infections (notably Mycoplasma and Epstein-Barr). They usually present as a self-limiting condition associated with a viral infection. Children under 2 years of age and adolescents frequently present chronic forms, associated or not, with systemic diseases, especially immunodeficiencies or autoimmune disorders. We present the case of an 11-year-old male patient, diagnosed with pneumonia with positive serologies for Mycoplasma and Cytomegalovirus, who developed autoimmune hemolytic anemia and required blood transfusion.

Current state and potential applications of neonatal Fc receptor (FcRn) inhibitors in hematologic conditions.

The neonatal fragment crystallizable (Fc) receptor (FcRn) transports IgG across mucosal surfaces and the placenta and protects IgG from degradation. Numerous clinical trials are investigating therapeutic FcRn inhibition for various immune-mediated neuromuscular and rheumatologic conditions; however, FcRn inhibition also represents a potential therapy for IgG-mediated hematologic conditions (e.g., immune thrombocytopenia, autoimmune hemolytic anemia, immune thrombotic thrombocytopenic purpura, acquired hemophilia, red blood cell/platelet alloimmunization). Current evidence derived from both in vitro and in vivo studies suggests that FcRn inhibitors effectively reduce total IgG levels without impacting its production or altering the levels of other immunoglobulin isotypes. Moreover, the risk of serious adverse events, including serious infections, appears to be lower than that seen with other commonly used immunomodulatory/immunosuppressive therapies, albeit in the setting of limited clinical trial data. Ultimately, additional clinical trials that include varied patient populations are required prior to incorporating these agents into standard treatment algorithms for most hematologic conditions. However, based on the pathophysiology of IgG-mediated hematologic disorders and the mechanism of action of FcRn inhibitors, these agents may represent a future novel therapeutic strategy for patients with hematologic conditions caused by IgG antibodies.

Paroxysmal Cold Hemoglobinuria: Mild to Catastrophic-Spectrum of a Rare Hemolytic Anemia of Childhood.

Paroxysmal cold hemoglobinuria (PCH) is among the rarest forms of autoimmune hemolytic anemia, most often seen in young children. PCH is caused by a biphasic immunoglobulin G antibody that binds to red cells at low temperatures and causes complement-mediated lysis as the temperature is raised. Diagnosis is based on high clinical suspicion followed by confirmation of the presence of Donath-Landsteiner antibodies. We have described 3 cases diagnosed with PCH over a span of 1 year, 2 cases presented with acute kidney injury with variable severity and needed hemodialysis. Another case showed prompt recovery with supportive treatment, suggesting variable severity of PCH. This report intends to generate awareness of this rare condition which is often misdiagnosed as nonspecific autoimmune hemolytic anemia and leads to unnecessary prolonged immunosuppressive therapy. It also emphasizes the rare possibility of the need for prompt renal replacement therapy in an otherwise benign self-limiting disorder.

The treatment of COVID-19-related autoimmune haemolytic anaemia

The treatment of COVID-19-related autoimmune haemolytic anaemia

Hypogammaglobulinemia in a child with atypical hemolytic-uremic syndrome

We present a unique clinical case of an atypical hemolytic-uremic syndrome in a child. The mutation in exon 6 of the CD46 gene (chr1:207940532G&gt;C) leads to a homozygous or hemizygous missense substitution. An 8-year-old girl was urgently hospitalized with symptoms of hemorrhagic syndrome and acute kidney injury. The child from the second pregnancy with an aggravated obstetric anamnesis, the first operative labor at the 38th week, who has an aggravated genealogical anamnesis. Initially, the disease developed in the guise of gastroenterological pathology: the girl had dyspeptic disorders, most likely associated with pathology of carbohydrate metabolism, also frequent infectious diseases and a lag in physical development. From the age of 4 years, the girl suffered from persistent hypoalbuminemia, hypoproteinemia and hypogammaglobulinemia, requiring replacement therapy with intravenous immunoglobulins. She was repeatedly examined in gastroenterological departments in Yekaterinburg and Moscow in 2021-2023, but no data concerning protein-losing enteropathies or primary immunodeficiency was obtained. Also, the whole-exome sequencing with result validation hasn’t confirmed an inherited etiology of the presumed congenital immune error. However, a CD46 gene mutation, associated with the development of hemolytic-uremic syndrome in some publications, was identified in the study. The signs of thrombotic microangiopathy were preceded by fever of unspecified etiology: microangiopathic hemolysis, thrombocytopenia, hyperazotemia, C3 consumption, proteinuria, and macrohematuria; hypercholesterolemia, protein metabolism disorder, increased transaminases, ferritin were also noted. According to the ultrasound of the kidneys there were diffuse changes in the parenchyma, decreased velocity indices of blood flow in both renal arteries at all levels. Differential diagnosis was carried out with thrombotic thrombocytopenic purpura, autoimmune hemolytic anemia, antinuclear form of atypical hemolytic-uremic syndrome, viral and bacterial infections, systemic pathology, antiphospholipid syndrome, and hemoblastosis. The girl didn’t need a renal replacement therapy. When complement-blocking therapy with eculizumab was initiated on vital indications, the signs of the disease were gradually eliminated. The prolonged absence of nephropathy in the child may indicate the diversity of the CD46 gene’s functions and different phenotypic manifestation of its mutations. Analysis of literature sources and detection of CD46 “environment” genes (CYBA, LYST, ARPCIB) by full-exome sequencing suggest ambiguity and polymorphism of phenotypic manifestations of complement-mediated mutation.

ABO-Mismatch Hematopoietic Stem Cell Transplantation with Pre-existing Red Cell Alloantibody Resembling a Case of Post-transplant Autoimmune Hemolytic Anemia

ABO-Mismatch Hematopoietic Stem Cell Transplantation with Pre-existing Red Cell Alloantibody Resembling a Case of Post-transplant Autoimmune Hemolytic Anemia

Chinese expert consensus on the diagnosis and treatment of Evans syndrome (2024)

Evans syndrome (ES) is a rare autoimmune disorder characterized by the presence of at least two autoimmune cytopenias (AIC), including immune thrombocytopenia (ITP), autoimmune hemolytic anemia (AIHA), and autoimmune neutropenia (AIN). Secondary ES accounts for 21%-50% of cases. ES is characterized by recurrent relapses, serious complications such as thrombosis and infection, and high mortality. The management of ES is highly heterogeneous, necessitating treatment for AIC, the primary disease, as well as associated complications. However, there remains a lack of prospective evidence, randomized clinical trials for ES. To standardize the diagnosis and management of ES in China effectively, this consensus was developed by the Red Blood Cell Diseases (Anemia) Group under the Chinese Society of Hematology within the Chinese Medical Association. It aims to provide valuable guidance for diagnosing and managing ES in clinical practice based on international consensus and comprehensive review of both domestic and international literature.