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

BACKGROUND: Autoimmune hemolytic anemia (AIHA) may be associated with transfusion reactions and risk of alloimmunization. OBJECTIVES: To evaluate the transfusion policy and rate of alloimmunization and its clinical significance in AIHA. METHODS: Data from 305 AIHA patients followed at a reference hematologic Center in Milan, Italy from 1997 to 2022 were retrospectively/prospectively collected (NCT05931718). RESULTS: 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. CONCLUSIONS: Severe symptomatic AIHA may be safely transfused provided appropriate matching of patients and donors.

Healthcare resource utilization of patients with warm autoimmune hemolytic anemia initiating first line therapy of oral corticosteroids with or without rituximab.

This retrospective cohort study described real-world treatment patterns and healthcare resource utilization (HCRU) of patients with warm autoimmune hemolytic anemia (wAIHA) initiating treatment with first-line (1L) oral corticosteroids (OCS) + rituximab (R) compared to 1L OCS. Patients with a wAIHA diagnosis code (D59.11) between 8/2020-3/2022 were identified using US pharmacy and medical claims databases. Patients initiating 1L OCS ± R were identified (date of initiation = 'index date') with a 1-year pre-index period and a variable (minimum 1-year) follow-up period. The final sample comprised 77 1L OCS + R patients and 400 1L OCS patients (~ 60% female, mean age > 64 years). Over the 1-year follow-up, HCRU was higher in the OCS + R cohort with higher mean number of physician office visits (22.9 and 14.4; p < 0.01), including hematology/oncology office visits, and higher utilization of rescue therapy (59.7% and 33.3%; p < 0.01), driven by higher use of injectable corticosteroids. Patients in OCS + R and OCS groups completed 1L therapy after a similar mean duration of 103.5 and 134.6 days, respectively (p = 0.24). In the majority of patients, second-line (2L) therapy was initiated at a similar timepoint: 66.2% OCS + R and 72.0% OCS cohorts (p = 0.31) initiated 2L in a mean of 218.3 and 203.2 days (p = 0.76) after the end of 1L treatment, respectively. The addition of rituximab in 1L did not extend the remission period, with most patients in both cohorts initiating 2L therapy within less than 1 year of completing 1L treatment. 1L OCS + R patients also had substantial HCRU burden. More effective novel therapies are needed to address the high unmet need in wAIHA.

Fatal co-infection by multiple pathogens in an indigenous woman with autoimmune hemolytic anemia and tuberculosis: a case report.

BACKGROUND: Tuberculosis (TB), one of the leading causes of death worldwide, has a higher incidence among indigenous people. Albeit uncommon, autoimmune hemolytic anemia (AIHA) has been deemed a risk condition to develop mycobacterial infection, as a result of the immunosuppressive treatments. TB, in turn, can be a predisposing factor for secondary infections. CASE PRESENTATION: Here we present a case of a 28-year-old indigenous woman from Colombia, previously diagnosed with AIHA and pulmonary TB. Despite various treatments, therapies and medical interventions, the patient died after severe medullary aplasia of multiple causes, including secondary myelotoxicity by immunosuppressive therapy and secondary disseminated infections, underlining infection by Staphylococcus aureus, Klebsiella pneumoniae and Candida glabrata, which were identified as drug-resistant microorganisms. Together, this led to significant clinical complications. Invasive aspergillosis was diagnosed at autopsy. CONCLUSIONS: This report presents a rarely finding of AIHA followed by TB, and highlights the great challenges of dealing with co-infections, particularly by drug resistant pathogens. It also aims to spur governments and public health authorities to focus attention in the prevention, screening and management of TB, especially among vulnerable communities, such as indigenous people.

A Multicentric Castleman Disease Associated with Mixed Warm and Cold Antibody-Mediated AHA Responsive to Siltuximab.

Castleman disease is non-clonal lymphoproliferative disorders defined by hypertrophy of lymph nodes. The multicentric form (MCD), in which multiple lymph node stations are involved, is not associated with HHV8 infection, but considered idiopathic, although IL-6 appears to play a central role in its pathogenesis. Here, we report the case of a patient who presented with mixed autoimmune hemolytic anemia (AIHA) and adenopathy that was very challenging to diagnose due to very low values of hemoglobin and refractoriness of obtaining any improvement of AIHA with standard first and second lines of therapy (steroids, rituximab, immunoglobulin, erythropoietin, and cyclosporine). When we safely proceeded to lymph node biopsy, a diagnosis of MCD was established. This permitted the treatment with siltuximab, an anti-IL-6 monoclonal antibody. After only 1 week, hemoglobin raised and he was discharged. After 1 year, he was still in remission. This case underlines the challenges in diagnosis of MCD, and the first case of response to siltuximab after the failure of rituximab to relieve mixed AIHA.

A national survey of current immunohematologic testing practices for the diagnosis of autoimmune hemolytic anemia in India.

Autoimmune hemolytic anemia (AIHA) is a common term for several disorders that differ from one another in terms of etiology, pathogenesis, clinical features, and treatment. Management of patients with AIHA has become increasingly evidence-based in recent years. While this development has resulted in therapeutic improvements, it also carries increased requirements for optimal diagnosis using more advanced laboratory tests. Unfortunately, limited data are available from developing countries regarding the testing and transfusion management of patients with AIHA. The main objective of this survey was to explore the current immunohematologic testing practices for the diagnosis of AIHA in India. This online survey consisted of 30 questions, covering the place of work, the number of AIHA cases encountered in the 3 preceding years, testing method(s), transfusion management, and so forth. Individuals representing 89 laboratories completed the survey; only 78 of which responded that AIHA testing was performed in their facility's laboratory. The majority of respondents agreed that the most commonly affected age-group comprised individuals of older than 20 years, with a female preponderance. Regarding transfusion management, respondents indicated that transfusion with "best-match" red blood cell units remains the most common practice. Column-agglutination technology is used by 92 percent of respondents as the primary testing method. Although a monospecific direct antiglobulin test is available at 73 percent of the sites, most of them have limited access to other resources that could diagnose cold or mixed AIHA. Merely 49 percent of responding laboratories have the resources to perform adsorption studies for the detection of alloantibodies. Furthermore, three-cell antibody screening reagents are unavailable at 32 percent of laboratories. In 72 percent of centers, clinical hematologists would prefer to consult a transfusion medicine specialist before administering treatment to AIHA patients. There is unanimous agreement regarding the need for a national registry. The survey data indicate wide variability in testing practices for patients with AIHA in India. Future studies are needed to focus on the feasibility and cost-effectiveness of different testing strategies for developing countries.

Autoimmune Hemolytic Anemia in the Pediatric Age Group: The Egyptian Experience.

Autoimmune hemolytic anemia (AIHA) is a common disease entity among adults; however, it is rare among the pediatric age group. Evidence is scarce regarding pediatric AIHA in the literature. The objective of this study is to assess the frequency of AIHA and describe the clinical and laboratory characteristics and treatment outcomes of a cohort of children with AIHA in Egypt. A retrospective study was conducted on 50 children with AIHA who were registered and followed up at the New Children's Hospital in Cairo, Egypt, between January 2010 and January 2021. The study group comprised 60% females and 40% males. Their median age was 8.25 years. All patients showed low hemoglobin levels with a mean of 5.40 ± 1.34 g/dl and a median reticulocyte count of 10 (IQR: 8-15). Twelve (24%) patients were diagnosed with Evans syndrome, and a positive Coombs test was detected in 46 patients (92%). The frequency of primary AIHA was 40%, whereas it was 60% for secondary AIHA. The first line of therapy for acute attacks was high-dose IV steroids which responded well in 38 (76%) patients. Secondary AIHA was more common among our children (60%). AIHA is more prevalent in females (60%). The clinical and laboratory characteristics matched previous reports.

Analysis of hematologic adverse events reported to a national surveillance system following COVID-19 bivalent booster vaccination.

Hematologic complications, including vaccine-induced immune thrombotic thrombocytopenia (VITT), immune thrombocytopenia (ITP), and autoimmune hemolytic anemia (AIHA), have been associated with the original severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. However, on August 31, 2022, new formulations of the Pfizer-BioNTech and Moderna vaccines were approved for use without clinical trial testing. Thus, any potential adverse hematologic effects with these new vaccines remain unknown. We queried the US Centers for Disease Control Vaccine Adverse Event Reporting System (VAERS), a national surveillance database, through February 3, 2023, all reported hematologic adverse events that occurred within 42 days of administration of either the Pfizer-BioNTech or Moderna Bivalent COVID-19 Booster vaccine. We included all patient ages and geographic locations and utilized 71 unique VAERS diagnostic codes pertaining to a hematologic condition as defined in the VAERS database. Fifty-five reports of hematologic events were identified (60.0% Pfizer-BioNTech, 27.3% Moderna, 7.3% Pfizer-BioNTech bivalent booster plus influenza, 5.5% Moderna bivalent booster plus influenza). The median age of patients was 66 years, and 90.9% (50/55) of reports involved a description of cytopenias or thrombosis. Notably, 3 potential cases of ITP and 1 case of VITT were identified. In one of the first safety analyses of the new SARS-CoV-2 booster vaccines, we identified few adverse hematologic events (1.05 per 1,000,000 doses), most of which could not be definitively attributed to vaccination. However, three reports of possible ITP and one report of possible VITT highlight the need for continued safety monitoring of these vaccines as their use expands and new formulations are authorized.

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

OBJECTIVE: To determine the predictors of the occurrence of severe autoimmune hemolytic anemia (AIHA) and its impact on damage accrual and mortality in SLE patients. METHODS: Factors associated with time to severe AIHA (hemoglobin level ≤7 g/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. RESULTS: 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 111 days (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. CONCLUSIONS: 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.

Molecular pharmacology in complement-mediated hemolytic disorders.

In the last decade, a deeper understanding of the pathogenesis of complement mediated hemolytic disorders, such as paroxysmal nocturnal hemoglobinuria (PNH), cold agglutinin disease (CAD), warm type autoimmune hemolytic anemia (AIHA) with complement activation (wAIHA), and atypical hemolytic uremic syndrome (aHUS), paved the way to the therapeutic shift from purely supportive approaches to complement-targeted therapies. This resulted in a significant improvement in disease management, survival, and quality of life. In this review, we will provide a snapshot of novel therapies for complement-mediated hemolytic anemias with a focus on those ready to use in clinical practice. C5 inhibitors eculizumab and the long-acting ravulizumab, are the established gold standard for untreated PNH patients, whilst the C3 inhibitor pegcetacoplan should be considered for suboptimal responders to anti-C5 drugs. Several additional compounds targeting the complement cascade at different levels (other C5 inhibitors, factor B and D inhibitors) are under active investigation with promising results. In CAD, immunosuppression with rituximab remains the first-line. However, recently FDA and EMA approved the anti-C1s monoclonal antibody, sutimlimab, that showed dramatic responses and whose regulatory approval is soon awaited in many countries. Other drugs under investigation in AIHA include the C3 inhibitor pegcetacoplan, and the anti-C1q ANX005 for warm AIHA with complement activation. Finally, aHUS is an indication for complement inhibitors. Eculizumab and ravulizumab have been approved, whilst other C5 inhibitors, and novel lectin pathway inhibitors are under active investigation in this disease.

Lupus low disease activity state as a treatment target for pediatric patients with lupus nephritis.

BACKGROUND: Lupus low disease activity state (LLDAS) is a treatment target for patients with SLE and is associated with decreased risk for severe flare and new damage. We investigated the utility of the achievement of LLDAS in children with lupus nephritis and whether attainment of LLDAS is associated with more favorable outcomes. METHODS: Data of children, diagnosed with biopsy-proven lupus nephritis between January 2012 and December 2020, were retrospectively analyzed. RESULTS: For patients who did not achieve LLDAS after initial treatment (first 6 months), presence of autoimmune hemolytic anemia (62% vs. 18%, p = 0.047), anti-Sm (85% vs. 18%, p = 0.003) and anti-dsDNA (77% vs. 27%, p = 0.038) antibodies, proliferative lupus nephritis (77% vs. 27%, p = 0.038), and hypertension (69% vs. 9%, p = 0.005) at onset were more frequently encountered. Also, a lower rate of complete kidney response (43% vs. 100%, p = 0.005) and a higher rate of hypertension (86% vs. 13%, p = 0.002) were observed in patients who did not achieve LLDAS-50, defined as being in LLDAS at least 50% of the observation time. Attainment of both LLDAS after initial treatment and LLDAS-50 were associated with lower rates of kidney flare (p = 0.001 and p = 0.002, respectively) and damage accrual (p = 0.007 and p = 0.02, respectively) through the observation period. CONCLUSIONS: LLDAS is an attainable treatment target for children with lupus nephritis and associated with lower rates of kidney flare and damage. Presence of hematologic involvement, hypertension, and proliferative lupus nephritis at onset adversely influenced the early achievement of LLDAS. A higher resolution version of the Graphical abstract is available as Supplementary information.

Aspects of laboratory characteristics, analysis of alloimmunization, and searching for predictors related to survival in patients with Autoimmune Hemolytic Anemia.

Autoimmune hemolytic anemia (AIHA) is characterized by hemolysis caused by autoantibodies. However, many patients do not respond to therapies and may have an unfavorable outcome. It has been hypothesized that patients with AIHA and alloantibodies have a lower survival compared to patients with this disease and without alloimmunization. To this end, the clinical and laboratory profile was described and sought to identify features associated with survival in patients with AIHA. This is a single-site retrospective observational study that included patients (children, adolescents, adults and elderly) diagnosed with AIHA from January 2000 to June 2019. Epidemiological data, laboratory tests, treatment response, alloantibody and autoantibody profile, red cell transfusion and clinical course were analyzed. Survival analysis was performed using Kaplan-Meier curves and Cox proportional hazards regression. The study included 138 patients, mostly caucasians and female. The median age at diagnosis was 48.5 years (0.16-88) and 82 (59.4 %) patients had secondary AIHA. In addition, 33 % (25/75) of subjects had alloantibodies at the time of AIHA diagnosis and 40 % (16/40) detected alloantibody emergence later. The overall 10-year survival rate was 51 % (median follow-up was 39 months). Monocytosis, IgM class autoantibody and Direct Antiglobulin Test (DAT) intensity had a significant impact on predicting mortality in this population. On the other hand, alloimmunization at diagnosis and after did not affect survival in this population.

The enhanced direct antiglobulin test in current practice has a limited impact on management of adult patients.

INTRODUCTION: The direct antiglobulin test (DAT) identifies immunoglobulin IgG and/or complement onthe red blood cell surface, allowing discrimination between immune and non-immunehemolysis. When the DAT is negative but there is clinical suspicion for immunehemolysis, an enhanced DAT can be sent to an immunohematology referencelaboratory (IRL). METHODOLOGY: This retrospective study assessed the volume of enhanced DATs at a large tertiarycare center and evaluated their impact on patient care. Enhanced DATs were sent on21 adult patients (January 2019 - January 2021) at the University of Pittsburgh MedicalCenter and Allegheny Health Network. Laboratory and clinical data were collected andanalyzed. RESULTS: Four out of 21 patients had positive tests (DAT and other serologic tests) at the localIRL. Enhanced DAT testing yielded positive results in an additional 5 patients butnegative or invalid results for 2 patients. High-dose steroid therapy was started in 12patients prior to receipt of enhanced DAT results. Enhanced DAT testing was sent amedian of 5 days after initiation of steroid therapy. For the patients trialed on steroids,the enhanced DAT results impacted medical decision-making in only 3 patients, and inonly one of those patients was the enhanced DAT positive despite a negative DAT at alocal IRL. In the non-steroid treated patients, enhanced DAT results did not contributeto clinical decision-making. CONCLUSION: Enhanced DATs generally did not impact medical decision-making in adults withhemolytic anemia.

Paroxysmal cold hemoglobinuria: A diagnostic dilemma in a paediatric patient.

BACKGROUND: Autoimmune hemolytic anaemia is rare in the paediatric population. Differentiation of the underlying aetiology is complicated by heterogeneity in diagnostic criteria and testing strategies. Paroxysmal cold hemoglobinuria (PCH) is an uncommon form of paediatric autoimmune hemolytic anaemia. Identification of the causative biphasic hemolysin requires clinical recognition and access to the Donath-Landsteiner (DL) test. CASE PRESENTATION: We report a young paediatric patient with no significant past medical history who presented with severe anaemia, jaundice, and dark urine following a respiratory illness. Initial laboratory evaluation showed a haemoglobin of 3.6 g/dL with plasma free haemoglobin 170 mg/dL (reference range <5 mg/dL), 3+ hemoglobinuria (reference range = 0), and direct antiglobulin testing (DAT) positive for complement component 3 (C3) only. Haemoglobin continued to decline following RBC transfusions using a blood warmer for presumed cold agglutinin syndrome. Subsequent testing at the reference laboratory revealed a DAT positive for C3 and immunoglobulin isotype G (IgG) and an eluate pan-agglutinin most consistent with a warm autoantibody, but the patient's anaemia was non-responsive to glucocorticoids and blood warmer cessation. However, a maximum cold agglutinin titre of 4 and absent thermal amplitude substantially weakened the evidence for the clinical significance of the cold autoantibodies. Consultation with the institutional transfusion medicine specialist prompted collection for the DL test, which demonstrated a definitive biphasic hemolysin consistent with PCH. DISCUSSION: Conflicting clinical and immunohematologic evidence can obscure the aetiology of autoimmune hemolysis, including concurrent warm and/or cold autoantibodies. Clinical correlation, consultation with the institutional transfusion service, and access to specialised testing are essential to establish the correct diagnosis.

Exacerbation of autoimmune hemolytic anemia associated with pure red cell aplasia after COVID-19: A case report.

Autoimmune hemolytic anemia (AIHA) and pure red cell aplasia (PRCA) are rare complications of coronavirus disease 2019 (COVID-19). Herein, we report the case of a 28-year-old Japanese man who showed severe AIHA exacerbation associated with PRCA after COVID-19. AIHA was diagnosed and maintained for 5 years. Approximately 4 weeks after COVID-19, the patient developed severe anemia (hemoglobin level, 3.4 g/dL). Laboratory test results confirmed hemolytic exacerbation of IgG-mediated warm-type AIHA. Despite the hemolysis phase, the bone marrow revealed extreme hypoplasia of erythroblasts with a decreased reticulocyte count, similar to that observed in patients with PRCA. During oral prednisolone treatment, the patient recovered from anemia and showed increased reticulocyte count and reduced hypoplasia of marrow erythroblasts. Exacerbation of AIHA and PRCA was triggered by COVID-19 because other causes were ruled out. Although this case report highlights that COVID-19 could lead to hematological complications such as AIHA and PRCA, the exact mechanisms remain unclear.

A 71-year-old male with a life-threatening recurrence of hemolytic anemia, thrombocytopenia, and acute kidney injury after pembrolizumab therapy: a case report.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. However, their use has been restricted in patients with preexisting autoimmune diseases due to concerns about increased risk of immune-related adverse events (irAEs). CASE PRESENTATION: We present a case of a patient with stage IV lung adenocarcinoma and a history of complement-mediated autoimmune hemolytic anemia in remission. After receiving a single dose of pembrolizumab, the patient experienced life-threatening recurrent hemolytic anemia, de novo thrombocytopenia, diarrhea, myocarditis, and acute kidney injury. Laboratory tests confirmed the diagnosis of Evan's syndrome, with positive PAIgG and direct antiglobulin test. Treatment with intravenous methylprednisolone at a dose of 2 mg/kg resulted in a favorable response, with resolution of symptoms and rapid recovery of kidney function. The probable cause of pre-renal hypoperfusion (evidenced by a BUN-to-creatinine ratio of 48.1) leading to acute tubular injury was attributed to pembrolizumab-induced diarrhea. CONCLUSIONS: This case illustrates a life-threatening recurrence of complement-mediated autoimmune hemolytic anemia induced by ICIs. Clinicians should carefully consider the expected efficacy and potential toxicity before initiating ICIs therapy in patients with preexisting autoimmune diseases. Additionally, the occurrence of acute kidney injury during ICIs therapy adds complexity and requires careful differential diagnosis.

Ultrastructural analysis of nucleated erythrocyte in patients with autoimmune hemolytic anemia (AIHA).

Autoimmune hemolytic anemia (AIHA) is a group of diseases characterized by immune-mediated lysis of mature red blood cells (RBCs). It is mainly classified into primary and secondary types based on etiology and mechanisms underlying autoantibody production. AIHA is diagnosed using morphological observation of bone marrow smears under a light microscope and monospecific direct antiglobulin test to detect hemolysis. Here, we retrospectively studied ultrastructural abnormalities of nucleated erythroid cells in bone marrows from 10 patients with AIHA using transmission electron microscopy. Our results revealed severe damage and injury to nucleated erythroid cells, including morphological irregularity, pyknosis, karyolysis, expansion of perinuclear cisternae and cytoplasmic lysis. These results indicate that aberrant immunity attacks not only mature RBCs but also nucleated erythroid cells, and ineffective hematopoiesis is partly involved in the pathogenesis of AIHA.

A rare case of complicated malaria presenting as warm autoimmune hemolytic anemia.

Autoimmune hemolytic anemia (AIHA) has been rarely reported worldwide or from India as the underlying cause of anemia in malaria. We hereby present a case of complicated Plasmodium falciparum malaria with concomitant warm AIHA in a 31-year-old male. Direct Antiglobulin Test (DAT) was positive and elution studies showed pan-agglutination reaction. Clinico-hematological and serological follow-up of the patient was done post artesunate treatment until day 9. We suggest that it is important to establish the immune basis of anemia in malaria patients for guiding the treatment plan for the clinicians and providing packed red blood cell transfusion if required.

[Warm autoimmune hemolytic anemia complicated with pulmonary hypertension exhibiting pulmonary mosaic attenuation pattern].

A 55-year-old man was admitted to our hospital with suspected hemolytic anemia. He was subsequently diagnosed with warm autoimmune hemolytic anemia complicated with pulmonary hypertension exhibiting a mosaic pattern on chest computed tomography. Treatment of hemolytic anemia rapidly improved pulmonary hypertension and the mosaic pattern. Pulmonary hypertension can also occur in patients with autoimmune hemolytic anemia.

[Novel anti-complement therapeutics for hemolytic anemia].

The anti-C5 antibody eculizumab was approved in 2007 as the first anti-complement agent for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). While eculizumab's indication has been expanded to include other diseases, the development of new anti-complement agents has been aggressively pursued for various diseases. In PNH, the anti-C5 recycling antibody ravulizumab, which is an improved version of eculizumab, has been developed, with an extended dosing interval of 2 to 8 weeks, vastly improving convenience. The treatment of PNH with terminal complement inhibitors such as eculizumab and ravulizumab presents a new challenge-extravascular hemolysis. To address this issue, the proximal complement inhibitor, a C3 inhibitor called pegcetacoplan, was approved in the United States of America. Furthermore, the amplification loop inhibitors-a factor B inhibitor iptacopan, and a factor D inhibitor danicopan-are being developed. Recently, the anti-C1s antibody sutimlimab was approved for the treatment of cold agglutinin disease, a type of autoimmune hemolytic anemia. This article discusses novel anti-complement therapies for hemolytic anemia.

[Autoimmune hemolytic anemia complicated with acute kidney injury and tubulopathy due to hemoglobin casts].

A 62-year-old male patient was admitted for close monitoring of anemia (hemoglobin level, 8.2 g/dl). Hemolytic anemia was observed; however, the direct antiglobulin test (DAT) result (standard tube method) was negative. Nevertheless, autoimmune hemolytic anemia (AIHA) was still suspected; therefore, a DAT (Colum method) and quantifying levels of red-blood-cell bound immunoglobulin G were performed, resulting in a definite diagnosis of warm AIHA. The patient also had an acute kidney injury (AKI) from the time of admission, which was poorly improved by supplemental fluids therapy alone. Therefore, renal biopsy was performed. Renal biopsy revealed acute tubular injury due to hemoglobin columns, and a diagnosed AKI caused by hemolysis due to AIHA. Following the definitive diagnosis of AIHA, the patient was treated with prednisolone, and after approximately 2 weeks, the anemia and nephropathy completely improved, which is maintained to this day. We report this case as a rare case of AKI induced by hemolysis of AIHA and a successful case of renal salvage by early administration of steroid.