Severe Autoimmune Hemolytic Anemia Research Articles

Severe, Refractory Primary Warm Autoimmune Hemolytic Anemia Requiring 90 Erythrocyte Transfusions.

A previously healthy 60-year-old man presented to the hospital with a hemoglobin of 3.5 g/dL. He was diagnosed with severe warm autoimmune hemolytic anemia (wAIHA) with reticulocytopenia on hospital day 1 that was not responsive to steroids, immune globulin, and rituximab. Over a 42-day hospital stay, the patient remained continuously transfusion-dependent with a ninety red cell unit requirement for his refractory disease. He was trialed on therapeutic plasma exchange before ultimately undergoing inpatient splenectomy that led to a response within hours. He remains in complete remission at six months of follow-up.

Aplastic Anaemia Associated with Bendamustine Therapy - A Rare Side Effect.

During treatment for malignant lymphoma, cytopenia can develop for several reasons. This can range from mild cytopenias leading to infection and bleeding to full-blown drug-induced aplastic anaemia. While aplastic anaemia affects individuals of all genders and ages, here, we describe aplastic anaemia after chemotherapy exposure to bendamustine in a 65-year-old female with non-Hodgkin's lymphoma. A 65-year-old woman with recurrent indolent marginal zone lymphoma and post-chemotherapy with bendamustine and rituximab, presented with a neutropenic fever and was admitted with a leading diagnosis of sepsis. In the previous two weeks, the patient required regular transfusions of packed red blood cells and platelets and maintained a daily ZARXIO® regimen. Laboratory results revealed pancytopenia, and broad-spectrum antibiotics (cefepime/vancomycin) were given. The patient was subsequently admitted to the hospital under the care of the haematology/oncology team and was ultimately diagnosed with aplastic anaemia, likely as a consequence of bendamustine chemoimmunotherapy. She elicited a positive response to the triple immunosuppressive therapy (IST) regimen (two immunotherapeutic agents plus one anti-thymocyte globulin (ATG), after which her cell counts returned to normal. This case underscores the importance of recognising haematologic complications linked to bendamustine and advocates for further research to increase the understanding among healthcare professionals of drug-induced aplastic anaemia. Bendamustine can cause severe autoimmune haemolytic anaemia and aplastic anaemia and may require multiple transfusions and a multidrug regimen for treatment. The use of ATG as a therapeutic intervention is appropriate because it has been effective in treating aplastic anaemia. Bendamustine can cause severe autoimmune haemolytic anaemia and aplastic anaemia, a side effect which has rarely been reported but is of significant clinical importance.Drug-induced aplastic anaemia is a complex, potentially devastating consequence of treating blood cancers and is a relatively unexplored area that requires further understanding.Anti-thymocyte globulin is effective in treating bendamustine-induced aplastic anaemia as it degrades lymphocytes that destroy the bone marrow.

Infectious Complications in Autoimmune Hemolytic Anemia: A Multi-Center Italian Experience

Introduction: Infections may play an important role in the development or relapse of autoimmune hemolytic anemia (AIHA) as well as possible complications of long-term immunosuppression secondary to its management. The prevalence and severity of infection in AIHA are still under-investigated. Methods: Hereby we studied retrospectively 324 patients older than 18 years old, diagnosed with AIHA and followed at 10 Italian centers between 1981 and 2022, focusing on infectious complications and their predictors. Results: At diagnosis, median age was 60 years (range 18-94), with 27% of patients older than 70 years and with a slight male predominance (65%) and classified as warm AIHA in 53% (Table 1). Median Hb was 7.3 g/dL (2-14), median WBC of 7,5x10 9/L (1,4-94) and median platelets of 260x10 9/L (4-695). Sixty-two (60%) out of 103 patients presented lymphopenia. Among 111 evaluable patients, reduced serum IgG/IgA/IgM levels were detected in 37%, 27%, and 23%, respectively. Twenty-nine (9%) patients had Evans Syndrome. During a median follow-up of 35 months (1-553 months), patients received a median of 1 line of therapy (1-7), including steroids, rituximab, chemotherapy, and immunosuppressive (IS) drugs in 90%, 45%, 10% and 12% of cases, respectively. Twenty (6%) patients underwent splenectomy and 43 (13%) received intravenous Ig supplementation. Sixty-five (20%) patients presented at least one infection episodes, with 17 experiencing recurrences. Pneumonia was the most frequent (44 cases), followed by 11 sepsis and 4 urinary tract infections, requiring hospitalization in 37 (71%) of cases. Pathogens were isolated in 23 patients (62% viral and 38% bacterial agents). Overall, 17 (16%) suffered from SARS-CoV-2 infection, of whom 8 requiring specific therapy. Eleven (18%) patients were receiving prophylaxis at the time of infection, including acyclovir (18%), cotrimoxazole (18%), both (55%) or anti-HBV prophylaxis (18%). Forty-seven (77%) patients were on active treatment for AIHA at the time of infection (32 steroids, 8 rituximab, 1 IS and 11 not specified), and 16 (25%) also experienced a thrombotic event. Patients receiving more than one therapy lines had 2-fold higher probability of developing infections (RR 2.03, 1.27-3.25, p=0,0017), particularly for those treated with IS (RR 1.77, 1.04-3.01, p=0,041) and with rituximab (RR 1.96, 1.20-3.20, p=0,0048). Among patients with infections, median time from the last dose of rituximab was 15 months (range 1-147 months). Moreover, patients with thrombotic events were more likely to experience infection episodes (RR 2.41, 1.52-3.83, p=0,001). During observation, 55 patients (23%) died, among them 10 for AIHA complications, including 6 infections. Conclusions: In conclusion, infections complicate about 20% of AIHA. Most episodes occurred during active AIHA-therapy and were more common in patients with prior exposure to rituximab or IS, suggesting an iatrogenic effect. The association with thrombotic events may indicate a relationship with more severe AIHA. Strategies to reduce the burden of IS in AIHA should be pursued.

Transfusions in autoimmune hemolytic anemias: Frequency and clinical significance of alloimmunization.

Autoimmune hemolytic anemia (AIHA) may be associated with transfusion reactions and risk of alloimmunization. To evaluate the transfusion policy and rate of alloimmunization and its clinical significance in AIHA. Data from 305 AIHA patients followed at a reference hematologic Center in Milan, Italy from 1997 to 2022 were retrospectively/prospectively collected (NCT05931718). Overall, 33% patients required transfusions with a response rate of 83% and eight transfusion reactions (7%), none hemolytic. Alloantibodies were detected in 19% of patients, being associated with higher transfusion burden (p=0.01), lower Hb increase post-transfusion (p=0.05), and transfusion reactions (p=0.04). Along decades, the rate of RBC transfusions decreased from 53% to 20% and that of alloimmunization dropped from 30% to 6% likely due to the adoption of prestorage leukoreduction, the use of more restrictive Hb thresholds, and the implementation of molecular typing. Severe symptomatic AIHA may be safely transfused provided appropriate matching of patients and donors.

COVID‑19 infection and severe autoimmune haemolytic anaemia: A case report and review of the literature

COVID‑19 infection and severe autoimmune haemolytic anaemia: A case report and review of the literature

Severe autoimmune hemolytic anemia; epidemiology, clinical management, outcomes and knowledge gaps.

Autoimmune hemolytic anemia (AIHA) is an acquired hemolytic disorder, mediated by auto-antibodies, and has a variable clinical course ranging from fully compensated low grade hemolysis to severe life-threatening cases. The rarity, heterogeneity and incomplete understanding of severe AIHA complicate the recognition and management of severe cases. In this review, we describe how severe AIHA can be defined and what is currently known of the severity and outcome of AIHA. There are no validated predictors for severe clinical course, but certain risk factors for poor outcomes (hospitalisation, transfusion need and mortality) can aid in recognizing severe cases. Some serological subtypes of AIHA (warm AIHA with complement positive DAT, mixed, atypical) are associated with lower hemoglobin levels, higher transfusion need and mortality. Currently, there is no evidence-based therapeutic approach for severe AIHA. We provide a general approach for the management of severe AIHA patients, incorporating monitoring, supportive measures and therapeutic options based on expert opinion. In cases where steroids fail, there is a lack of rapidly effective therapeutic options. In this era, numerous novel therapies are emerging for AIHA, including novel complement inhibitors, such as sutimlimab. Their potential in severe AIHA is discussed. Future research efforts are needed to gain a clearer picture of severe AIHA and develop prediction models for severe disease course. It is crucial to incorporate not only clinical characteristics but also biomarkers that are associated with pathophysiological differences and severity, to enhance the accuracy of prediction models and facilitate the selection of the optimal therapeutic approach. Future clinical trials should prioritize the inclusion of severe AIHA patients, particularly in the quest for rapidly acting novel agents.

Outcomes of therapeutic plasma exchange in severe autoimmune hemolytic anemia hospitalizations: An analysis of the National Inpatient Sample.

Autoimmune hemolytic anemia (AIHA) is characterized by humoral and/or cellular immune-mediated hemolysis of red blood cells. The role of therapeutic plasma exchange (TPE) in AIHA is unclear. We queried the National Inpatient Sample (NIS) for 2002-2019 to identify hospitalizations with the primary diagnosis of AIHA. We included hospitalizations with the highest severity subclass identified by All Patient Refined Disease Related Group (APR-DRG). We used multivariate regression analysis to compare in-hospital mortality and other relevant in-hospital outcomes between hospitalizations that received TPE and those that did not. We identified 255 weighted hospitalizations in the TPE group and 4973 in the control group. Those in the control group were older (median age 67 vs. 48 years, p < .001) and had a higher prevalence of most comorbidities. The TPE group had higher odds of all-cause in-hospital mortality (odds ratio [OR], 1.59; 95% confidence interval [CI], 1.19-2.11). They also had higher rates of many secondary outcomes, including requiring mechanical ventilation, developing circulatory shock, acute stroke, urinary tract infections, intracranial hemorrhage, acute kidney injury, and requiring new hemodialysis. No significant differences were noted in the rates of acute myocardial infarctions, bacterial pneumonia, sepsis/septicemia, thromboembolic events, and other bleeding events. Furthermore, the TPE group had a higher median length of hospital stay (19 vs. 9 days, p < .001). Hospitalizations with severe AIHA that received TPE had higher rates of adverse in-hospital outcomes.

Severe autoimmune intravascular hemolytic anemia in patients receiving alemtuzumab for multiple sclerosis.

Severe autoimmune intravascular hemolytic anemia in patients receiving alemtuzumab for multiple sclerosis.

Diagnostic and Treatment Challenges in a Pediatric Patient with Progressive Refractory ALPS-like Disease

Introduction: Diagnostic criteria for Autoimmune Lymphoproliferative Syndrome (ALPS) is based on clinical, laboratory and genetic findings. The underlying pathomechanisms are largely related to defects in the lymphocyte apoptosis pathways (FAS, FAS ligand, or CASP10) but other combined immunodeficiencies may also present with ALPS-like features (e.g. CASP8, NFKB1, CTLA4, ALP1). Clinically, patients often present with progressive autoimmune cytopenias and treatment relies on T cell immune modulation. Hereby, we present diagnostic and treatment challenges in a pediatric patient with ALPS-like phenotype with rapid decline during an episode of severe autoimmune hemolytic anemia. MethodsRetrospective chart review for clinical and laboratory data. Deep immune phenotyping was obtained for T, B and NK cells subsets at several timepoints during the acute illness. Genetic evaluation for both germline and somatic mutations were pursued.Case presentation: Patient is an 11-year-old Syrian male of consanguineous parents who presented at age 6 with immune thrombocytopenic purpura (ITP) and met criteria for ALPS with required criteria (chronic lymphadenopathy and increased T Cell Receptor αβ CD4-CD8- double negative T cells (TCRαβDNT) (4.2%, normal <2%), primary accessory criteria (defective lymphocyte apoptosis twice) and secondary accessory criteria (elevated B12, IgG and FAS-L). Panel sequencing (207 genes of inborn errors of immunity) and later Whole Exome Sequencing were both unrevealing. At 11 years of age, he was admitted with a Coombs positive severe autoimmune hemolytic anemia (hemoglobin of 3.5) that was complicated by EBV and parvovirus viremia, and aplastic anemia. Treatment course was complex including steroid, high dose IvIg, rituximab, sirolimus, mycophenolate mofetil, eculizumab, and epoetin alpha. Biomarkers of immune dysregulation, such as TCRαβDNT, follicular helper T cells and CD19hiCD21lo B cells were monitored closely and improved on therapy. Total T cell, CD4, CD8, and Treg populations were all initially low but returned to baseline following combined treatment. Screening for somatic mutations and whole genome sequencing is ongoing. Discussion/ConclusionOur case highlights the diagnostic and treatment challenges in a pediatric patient with ALPS-like Disease. Cellular biomarkers may guide therapy if autoimmune cytopenia recurs. Somatic and germline testing is needed to understand the underpinning of this disorder and may further guide treatment strategies.

Paediatric autoimmune diseases with ELANE mutations associated with neutropenia

ObjectiveTo explore the clinical characteristics of autoimmune diseases in children with ELANE mutations.MethodsThree cases of children with ELANE mutations manifesting as autoimmune diseases, who were under treatment from April 2020 to May 2021, were retrospectively analysed.ResultsAmong the three children, two were boys aged 15 years and 22 months (cases 1 and 3) respectively, and the other one was a 22-month-old girl (case 2). All the cases had recurrent infections. Case 1 presented with cyclic neutropenia and systemic lupus erythematosus (SLE). Case 2 presented with severe neutropenia and autoimmune haemolytic anaemia (AHIA). Case 3 presented with severe neutropenia and anti-neutrophil cytoplasm antibodies (ANCA)-associated small vasculitis. Genetic tests showed that they all had heterozygous mutations in the ELANE gene. Case 1 was treated with methylprednisolone and hydroxychloroquine sulphate for 2 years, making neutrophil level return to normal. Case 2 received allogeneic hematopoietic stem cell transplantation and has stopped taking antibiotics, steroids and all the immunosuppressors. Case 3 received subcutaneous injections of granulocyte colony-stimulating factor, oral prednisone and cyclophosphamide. The boy in case 3 has been followed up for one year, and his absolute neutrophil count has increased to 1.56 × 109/L.ConclusionPatients with ELANE mutations, combined with autoimmune diseases, may have recurrent infections. Disease-modifying antirheumatic drugs (DMARDs) are effective for autoimmune diseases. Autoimmune diseases with ELANE mutations associated with neutropenia can be cured through allogeneic hematopoietic stem cell transplantation.

The choice of new treatments in autoimmune hemolytic anemia: how to pick from the basket?

Autoimmune hemolytic anemia (AIHA) is defined by increased erythrocyte turnover mediated by autoimmune mechanisms. While corticosteroids remain first-line therapy in most cases of warm-antibody AIHA, cold agglutinin disease is treated by targeting the underlying clonal B-cell proliferation or the classical complement activation pathway. Several new established or investigational drugs and treatment regimens have appeared during the last 1-2 decades, resulting in an improvement of therapy options but also raising challenges on how to select the best treatment in individual patients. In severe warm-antibody AIHA, there is evidence for the upfront addition of rituximab to prednisolone in the first line. Novel agents targeting B-cells, extravascular hemolysis, or removing IgG will offer further options in the acute and relapsed/refractory settings. In cold agglutinin disease, the development of complement inhibitors and B-cell targeting agents makes it possible to individualize therapy, based on the disease profile and patient characteristics. For most AIHAs, the optimal treatment remains to be found, and there is still a need for more evidence-based therapies. Therefore, prospective clinical trials should be encouraged.

Case Report] Challenging Detection of Latent Tuberculosis in a Patient Undergoing High-Dose Corticosteroid Therapy for Acute Hemolytic Anemia and Rhupus Arthropathy

Acute autoimmune hemolytic anemia requires rapid stabilization, typically through the administration of high-dose corticosteroids. However, it is important to consider reactivation of latent infection and how immune suppression can interfere with molecular screening tools. In this case report, we present a patient with Rheumatoid Arthritis/Systemic Lupus Erythematosus experiencing severe autoimmune hemolytic anemia complicated by an unknown latent tuberculosis infection.

Predictors of severe hemolytic anemia and its impact on major outcomes in systemic lupus erythematosus: Data from a multiethnic Latin American cohort.

To determine the predictors of the occurrence of severe autoimmune hemolytic anemia (AIHA) and its impact on damage accrual and mortality in SLE patients. Factors associated with time to severe AIHA (hemoglobin level ≤7g/dL) occurring from the onset of SLE symptoms were examined by Cox proportional hazards regressions. The association of severe AIHA with mortality was examined by logistic regression analyses while its impact on damage was by negative binomial regression. Of 1,349 patients, 49 (3.6%) developed severe AIHA over a mean (SD) follow-up time of 5.4 (3.8) years. The median time from the first clinical manifestation to severe AIHA was 111days (IQR 43-450). By multivariable analysis, male sex (HR 2.26, 95% CI 1.02-4.75, p = 0.044), and higher disease activity at diagnosis (HR 1.04, 95% CI 1.01-1.08, p = 0.025) were associated with a shorter time to severe AIHA occurrence. Of the SLEDAI descriptors, only hematologic (leukopenia and/or thrombocytopenia) showed a certain trend toward significance in the multivariable analysis (HR 2.36, 95% CI 0.91-6.13, p = 0.0772). Severe AIHA contributed neither to damage nor to mortality. Severe AIHA occurs during the early course of SLE. Male sex and higher disease activity at diagnosis emerged as independent predictors of a shorter time to severe AIHA occurrence. Although not statistically significant, hematological abnormalities at SLE diagnosis could predict the occurrence of severe AIHA in a shorter time. Damage and mortality did not seem to be impacted by the occurrence of severe AIHA.

Case Report] Challenging Detection of Latent Tuberculosis in a Patient Undergoing High-Dose Corticosteroid Therapy for Acute Hemolytic Anemia and Rhupus Arthropathy

Acute autoimmune hemolytic anemia requires rapid stabilization, typically through the administration of high-dose corticosteroids. However, it is important to consider reactivation of latent infection and how immune suppression can interfere with molecular screening tools. In this case report, we present a patient with Rheumatoid Arthritis/Systemic Lupus Erythematosus experiencing severe autoimmune hemolytic anemia complicated by an unknown latent tuberculosis infection.

Plasmodium vivax Malaria Associated with Severe Autoimmune Hemolytic Anemia

Background: Severe and/or persistent anemia due to autoimmune hemolytic anemia (AIHA) secondary to vivax malaria is a rare association. Very few cases are reported worldwide, and even less from India. AIHA occurs when immunoglobulins and/or complements target red blood cell surface antigens resulting in hemolysis. Awareness of this complication helps in early recognition, investigation, and prompt initiation of treatment. Clinical Description: A 15-year-old boy presented with a history of high fever associated with chills for 2 days. Examination revealed the presence of severe pallor and icterus. Systemic examination was unremarkable. Investigations showed anemia (Hb: 3.6 g/dl) with reticulocytosis (6.6%), malaria (trophozoites of Plasmodium vivax and antigen test positive), and indirect evidence of hemolysis (indirect hyperbilirubinemia and elevated lactate dehydrogenase of 668 U/l). Management and Outcome: Treatment was started with intravenous artesunate and packed cells transfusion was planned. Cross-matching showed autoantibodies which raised suspicion of AIHA. Coomb's test was positive. Least incompatible packed red blood cells were transfused. A repeat peripheral smear was negative for malaria. Posttransfusion, the Hb levels rose to 8.3 g/dl before falling to 5.3 g/dl over the next 2 days. The direct antiglobulin test was positive. High doses of oral prednisolone resulted in progressive improvement in Hb levels to 8 g/dl within a week. He was discharged on oral prednisolone with daily oral folic acid supplements. The steroids were tapered when Hb reached 10.6 g/dl and continued for 3 months. Conclusion: If a patient with malaria (falciparum or vivax) exhibits persistent severe anemia, indirect evidence of hemolysis is found on investigations and/or autoantibodies identified on cross-matching, AIHA should be suspected and investigated accordingly.

Autoimmune Hemolytic Anemia After Inactivated Virus COVID-19 Vaccination: A Report of 2 Cases

Very few cases of autoimmune hemolytic anemia (AIHA) have been reported after mRNA COVID-19 vaccinations. But herein we found 2 cases of AIHA after inactivated virus COVID-19 vaccination. Case 1: a 47-year-old Thai woman suffered from malaise, fatigue, and feverish feeling since the evening of the day of the first dose of inactivated virus COVID-19 vaccination (Sinopharm). She did not have any serious health problem prior this illness. Physical examination revealed marked pallor and body temperature was 38.1°C. Blood tests showed hemoglobin (Hb) 55 g/L, white blood cell (WBC) 12.2 × 109/L, platelet 310 × 109/L, nucleated red blood cell (RBC) 8/100 WBC, reticulocyte count 25.0%, direct antiglobulin test-4+ positive, indirect antiglobulin test-2+ positive. She was diagnosed with severe AIHA and well responsive to steroid therapy. Case 2: a 78-year-old Thai woman felt fatigue without fever 3 days after the second dose of inactivated virus COVID-19 vaccine (Sinopharm). Her underlying disease was anemia of the elderly with alpha thalassemia-1 heterozygosity. Her averaged Hb concentration before transfusion was 85 ± 3 g/L and she always needed transfusion every 2 months. Physical examination revealed only pallor. Blood test showed Hb 79 g/L, WBC 3.7 ×109/L, platelet 104 × 109/L, direct antiglobulin test-4+ positive, indirect antiglobulin test-4+ positive. She was diagnosed with AIHA and treated with cyclophosphamide and blood transfusion. Although the association between the inactivated virus COVID-19 vaccination and AIHA could not be simply concluded and the mix-and-match combination of different COVID-19 vaccines is promoted by Thai government, both of our patients chose to postpone the next dose of any kind of COVID-19 vaccine.

P1530: PERITRANFUSIONAL C1-INHIBITOR IN PATIENTS WITH SEVERE COMPLEMENT-MEDIATED AUTOIMMUNE HEMOLYTIC ANEMIA: AN OPEN LABEL PHASE 2 TRIAL.

Background: Complement-mediated autoimmune hemolytic anemia (AIHA) is characterized by destruction of red blood cells (RBCs) due to autoantibodies that initiate complement activation via the classical pathway. This may result in fulminant intra- and extravascular hemolysis with need for RBC transfusions, of which the efficacy can be compromised by the antibodies reacting with donor RBCs. Hemolysis induces a pro-inflammatory response that can contribute to hypercoagulability, as seen in patients with other complement-mediated hemolytic disorders such as paroxysmal nocturnal hemoglobinuria. C1-inhibitor (C1-INH; Cinryze) is an endogenous plasma regulator of the classical and lectin complement pathway approved for patients with hereditary angioedema. In a single case report and in vitro, we observed that C1-INH administration attenuated complement deposition on RBCs and subsequent hemolysis. Therefore, we hypothesized that peritransfusional administration of C1-INH in complement AIHA would reduce complement activation and hemolysis and thus improve transfusion outcome. Aims: To assess the efficacy and safety of intravenous C1-INH in patients with transfusion-dependent complement-mediated AIHA on parameters for hemolytic activity, complement activation and inflammation. Methods: We conducted a prospective, single center, phase 2 open label trial. Patients with AIHA and confirmed C3c/d-positive direct antiglobulin test, baseline hemoglobin (Hb) of ≤8 g/dL and an indication for ≥ two RBC transfusion units were included after informed consent. Treatment consisted of four peritransfusional doses of C1-INH intravenously (6000, 3000, 2000 and 1000 U) with 12 hour (hr) intervals. Blood samples at 0, 12, 24, 36, 48, 72 hrs, 7 and 14 days were analyzed for hemolytic parameters, RBC opsonization and markers of complement activation and systemic inflammation (nucleosomes and human neutrophil elastase-α1-antitrypsin complexes (HNE-α1-ATc)). Safety was monitored and scored (CTCAE version 4.0). Results: Ten patients were included in the study. At baseline, we found increased complement C3d, IgG and IgM deposition on RBCs compared to healthy controls (p=0.002, 0.005 and 0.002). Circulating C3b/c levels, nucleosomes and HNE-α1-ATc were increased compared to healthy controls (p<0.001, p=0.046 and p=0.001). C1-INH administration resulted in an increase of C1-INH antigen and -activity, peaking at 48 hrs (Fig. A). At 48 hrs after first administration, treatment significantly reduced C3d deposition on RBCs (-21%, p=0.016), but not systemic complement activation as shown by C3b/c levels (-14.96 nM, p=0.874; Fig. B). With declining C1-INH levels, C3 deposition increased again. Shortly after transfusion, Hb increased (1.59 g/dL at 12 h; p=0.008), but at 48 hrs, hemolytic and inflammation parameters did not improve (LDH -169.5 U/L, p=0.572; bilirubin total -4.306 µmol/L, p=0.987; Hb -1.217 g/dL; p=0.056; nucleosomes -17%, p=0.938; HNE-α1-ATc +21%;, p=0.297; Fig. C, D). No serious adverse events were reported. Image:Summary/Conclusion: Peritransfusional C1-INH in AIHA temporarily reduced local complement activation as evidenced by C3d deposition on RBCs, but did not affect hemolysis or systemic complement activation. Increased Hb levels at later timepoints were observed, but this effect might be confounded by additional treatments and transfusions. In conclusion, we found no (clinically) significant effect of C1-INH on hemolysis and systemic complement activation. This may be explained by the dosing of C1-INH, which possibly was too low to counter the severe complement-mediated AIHA and additional transfusion effects.

TLR8/TLR7 dysregulation due to a novel TLR8 mutation causes severe autoimmune hemolytic anemia and autoinflammation in identical twins.

Our study presents a novel germline c.1715G>T (p.G572V) mutation in the gene encoding Toll-like receptor 8 (TLR8) causing an autoimmune and autoinflammatory disorder in a family with monozygotic male twins, who suffer from severe autoimmune hemolytic anemia worsening with infections, and autoinflammation presenting as fevers, enteritis, arthritis, and CNS vasculitis. The pathogenicity of the mutation was confirmed by in vitro assays on transfected cell lines and primary cells. The p.G572V mutation causes impaired stability of the TLR8 protein, cross-reactivity to TLR7 ligands and reduced ability of TLR8 to attenuate TLR7 signaling. This imbalance toward TLR7-dependent signaling leads to increased pro-inflammatory responses, such as nuclear factor-κB (NF-κB) activation and production of pro-inflammatory cytokines IL-1β, IL-6, and TNFα. This unique TLR8 mutation with partial TLR8 protein loss and hyperinflammatory phenotype mediated by TLR7 ligands represents a novel inborn error of immunity with childhood-onset and a good response to TLR7 inhibition.

Characteristics and Outcome of Adults with Severe Autoimmune Hemolytic Anemia Admitted in Intensive Care Unit: Results from a Large French Observational Study

Characteristics and Outcome of Adults with Severe Autoimmune Hemolytic Anemia Admitted in Intensive Care Unit: Results from a Large French Observational Study

A Case of COVID-19 Infection Associated with Severe Cold Agglutinin Autoimmune Haemolytic Anaemia

COVID-19 is known to cause systemic disease with multiple organ dysfunctions. COVID-19 associated immune-mediated phenomena such as autoimmune haemolytic anaemia has been identified previously with rare incidence. However, the association between COVID-19 infection and autoimmune haemolytic anaemia is not fully evaluated.