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.

Autoimmune Hemolytic Anemias: Classifications, Pathophysiology, Diagnoses and Management.

Autoimmune hemolytic anemias (AIHAs) are conditions involving the production of antibodies against one's own red blood cells (RBCs). These can be primary with unknown cause or secondary (by association with diseases or infections). There are several different categories of AIHAs recognized according to their features in the direct antiglobulin test (DAT). (1) Warm-antibody AIHA (wAIHA) exhibits a pan-reactive IgG autoantibody recognizing a portion of band 3 (wherein the DAT may be positive with IgG, C3d or both). Treatment involves glucocorticoids and steroid-sparing agents and may consider IVIG or monoclonal antibodies to CD20, CD38 or C1q. (2) Cold-antibody AIHA due to IgMs range from cold agglutinin syndrome (CAS) to cold agglutin disease (CAD). These are typically specific to the Ii blood group system, with the former (CAS) being polyclonal and the latter (CAD) being a more severe and monoclonal entity. The DAT in either case is positive only with C3d. Foundationally, the patient is kept warm, though treatment for significant complement-related outcomes may, therefore, capitalize on monoclonal options against C1q or C5. (3) Mixed AIHA, also called combined cold and warm AIHA, has a DAT positive for both IgG and C3d, with treatment approaches inclusive of those appropriate for wAIHA and cold AIHA. (4) Paroxysmal cold hemoglobinuria (PCH), also termed Donath-Landsteiner test-positive AIHA, has a DAT positive only for C3d, driven upstream by a biphasic cold-reactive IgG antibody recruiting complement. Although usually self-remitting, management may consider monoclonal antibodies to C1q or C5. (5) Direct antiglobulin test-negative AIHA (DAT-neg AIHA), due to IgG antibody below detection thresholds in the DAT, or by non-detected IgM or IgA antibodies, is managed as wAIHA. (6) Drug-induced immune hemolytic anemia (DIIHA) appears as wAIHA with DAT IgG and/or C3d. Some cases may resolve after ceasing the instigating drug. (7) Passenger lymphocyte syndrome, found after transplantation, is caused by B-cells transferred from an antigen-negative donor whose antibodies react with a recipient who produces antigen-positive RBCs. This comprehensive review will discuss in detail each of these AIHAs and provide information on diagnosis, pathophysiology and treatment modalities.

A nanobody-based complement inhibitor targeting complement component 2 reduces hemolysis in a complement humanized mouse model of autoimmune hemolytic anemia.

C2 is an attractive therapeutic target for many complement-mediated diseases. We developed Nab1B10, a new anti-C2 nanobody that potently and selectively inhibits both the classical and lectin pathways of complement activation. Mechanistically, Nab1B10 binds to the C2a portion of C2 and inhibits the assembly of C3 convertase C4b2a. Nab1B10 cross-reacts with monkey but not rodent C2 and inhibits classical pathway-mediated hemolysis. Using a new complement humanized mouse model of autoimmune hemolytic anemia (AIHA), we demonstrated that Nab1B10 abolished classical pathway complement activation-mediated hemolysis in vivo. We also developed C2-neutralizing bi- and tetra-valent antibodies based on Nab1B10 and found these antibodies significantly more potent than the other anti-C2 monoclonal antibody that is already in clinical trials. These data suggest that these novel C2-neutralizing nanobodies could be further developed as new therapeutics for many complement-mediated diseases, in which pathogenesis is dependent on the classical and/or lectin pathway of complement activation.

Paediatric-onset Evans syndrome: Breaking away from refractory immune thrombocytopenia.

Since its first description by Evans in 1951, this syndrome has been linked to chronic immune thrombocytopenia with the concurrent or delayed onset of autoimmune haemolytic anaemia or neutropenia. For decades, the evolution of Evans syndrome (ES) has carried a poor prognosis and often resulted in chronic steroid exposure, multiple immune suppressing medications directed against T or B lymphocytes, and splenectomy. This paper presents a new view of ES based on recent advances in genomics which begin to classify patients based on their underlying molecular variants in previously described primary immune disorders. This has opened up new avenues of targeted therapy or bone marrow transplant at rather than broad long-term immune suppression or splenectomy. Importantly, recent studies of the full lifespan of ES suggest that at least 80% of those paediatric patients will progress to various clinical or biological immunopathological manifestations with age despite the resolution of their cytopenias. Those patients merit long-term follow-up and monitoring in dedicated transition programs to improve outcome at the adult age.

The potential of metabolomics as a predictive guide for clinical management in autoimmunity against red blood cells.

Autoimmune-responses leading to increased destruction of red blood cells occur in autoimmune haemolytic anaemia (AIHA). The pathophysiology of AIHA is multifactorial and not fully understood, and clinically it remains challenging to manage relapsed and treatment-refractory cases. Rabelo and colleagues conduct metabolomic profiling in plasma of 26 patients with primary warm AIHA, with consideration of haemolytic activity and relapse occurrence. They identify distinct metabolites to be increased in primary warm AIHA patients, thereby providing an encouraging basis for further validation and exploration of metabolomic profiling as a predictive tool for the management of AIHA. Commentary on: Rabelo et al. Metabolomic profile in patients with primary warm autoimmune haemolytic anaemia. Br J Haematol 2023;200:140-149.

Metabolomic profile in patients with primary warm autoimmune haemolytic anaemia.

Autoimmune haemolytic anaemia (AIHA) is a rare clinical condition with immunoglobulin fixation on the surface of erythrocytes, with or without complement activation. The pathophysiology of AIHA is complex and multifactorial, presenting functional abnormalities of T and B lymphocytes that generate an imbalance between lymphocyte activation, immunotolerance and cytokine production that culminates in autoimmune haemolysis. In AIHA, further laboratory data are needed to predict relapse and refractoriness of therapy, and thus, prevent adverse side-effects and treatment-induced toxicity. The metabolomic profile of AIHA has not yet been described. Our group developed a cross-sectional study with follow-up to assess the metabolomic profile in these patients, as well as to compare the metabolites found depending on the activity and intensity of haemolysis. We analysed the plasma of 26 patients with primary warm AIHA compared to 150 healthy individuals by mass spectrometry. Of the 95 metabolites found in the patients with AIHA, four acylcarnitines, two phosphatidylcholines (PC), asymmetric dimethylarginine (ADMA) and three sphingomyelins were significantly increased. There was an increase in PC, spermine and spermidine in the AIHA group with haemolytic activity. The PC ae 34:3/PC ae 40:2 ratio, seen only in the 12-month relapse group, was a predictor of relapse with 81% specificity and 100% sensitivity. Increased sphingomyelin, ADMA, PC and polyamines in patients with warm AIHA can interfere in autoantigen and autoimmune recognition mechanisms in a number of ways (deficient action of regulatory T lymphocytes on erythrocyte recognition as self, negative regulation of macrophage nuclear factor kappa beta activity, perpetuation of effector T lymphocyte and antibody production against erythrocyte antigens). The presence of PC ae 34:3/PC ae 40:2 ratio as a relapse predictor can help in identifying cases that require more frequent follow-up or early second-line therapies.

Maintenence rituximab following induction in autoimmune cytopenias.

About 50% of immune thrombocytopenia (ITP) patients respond to rituximab induction, but most relapse. The effectiveness of rituximab maintenance remains untested. This study included autoimmune cytopenia patients who had previously responded to rituximab induction but subsequently relapsed. After re-induction, patients received rituximab maintenance regimen consisting of a single 375 mg/m2 dose administered at 4 month intervals, with a maximum of 6 doses. Primary endpoints were duration of response and safety. Sixteen patients: ITP (9), autoimmune haemolytic anaemia (2), and Evans syndrome (5) received rituximab maintenance. 15/16 achieved complete response (CR); 8/15 CR + 1 partial reponse remain in remission. Median response: 43 months; estimated 5-year relapse-free >50%. Three developed hypogammaglobulinemia. Rituximab maintenance led to prolonged remissions in patients with autoimmune cytopenias who had previously responded to rituximab induction.

Warm autoimmune hemolytic anemia with anti-Jka specificity following babesiosis masquerading as a delayed hemolytic transfusion reaction.

BACKGROUND: Warm autoimmune hemolytic anemia (WAIHA) is characterized by the development of autoantibodies that react with red blood cells (RBCs) optimally at physiologic temperature, classically resulting in a positive direct antiglobulin test (DAT) for IgG and a panreactive eluate. Babesiosis has been described as a potentiator of WAIHA, and all cases have shown classic blood bank findings. Only rare reports have described autoantibodies, both secondary to babesiosis and overall, with specificity for Kidd antigens. METHODS: Antibody detection and identification were performed using IgG-specific column agglutination technology. Jka antigen phenotyping was assessed using monoclonal reagents and genotypic analysis was performed at an immunohematology reference laboratory. DATs were performed via standard tube methods. The elution was performed using the ELUclear glycine acid red cell elution kit. RESULTS: We report a case of WAIHA induced by Babesia microti infection with an autoantibody with Jka specificity, originally believed to be a delayed hemolytic transfusion reaction, given the detection of an RBC antibody in close proximity to numerous RBC transfusions. Determination of autoantibody status with anti-Jka -like reactivity was only confirmed after Kidd antigen genotyping predicted expression of the Jka antigen. DISCUSSION: Healthcare providers should be cognizant of the potential for babesiosis-induced WAIHA, particularly in individuals who continue to hemolyze despite undetectable parasitemia. Furthermore, this case highlights the possibility for warm autoantibodies to demonstrate Kidd antigen specificity. Though Kidd antigen variants are rare, antigen genotyping may be beneficial, particularly in the context of recent RBC transfusions, which typically preclude accurate serological phenotypic assessment.

The experience of flow cytometry for specific antibody against cisplatin-treated red blood cells: A case report.

BACKGROUND: Cisplatin-associated hemolysis is a rare but important adverse effect. Nonimmunological protein adsorption (NIPA) due to erythrocyte membrane modification has been reported as the leading cause of cisplatin-associated hemolysis. However, limited data exist on cisplatin-associated immunological hemolysis because of a lack of an established diagnostic method. Here, we used flow cytometry (FCM) to diagnose a patient with cisplatin-associated immunological hemolysis. STUDY DESIGN AND METHODS: A 55-year-old woman with uterocervical cancer was treated with weekly cisplatin monotherapy (40 mg/m2 ). She had no previous transfusion and medication history, nor any significant family history. On the 26th day after cisplatin administration, severe hemolysis was noted. Her red blood cells (RBCs) and sera were evaluated by direct antiglobulin test (DAT) and indirect antiglobulin test (IAT), respectively. To explore immunological reactions for cisplatin-treated RBCs, we attempted FCM using cisplatin-treated and -untreated RBCs. After incubating conditioned RBCs with the patient's serum or healthy donor serum, we evaluated their fluorescent intensity by fluorescein isothiocyanate (FITC)-conjugated anti-human immunoglobulin (Ig) G antibodies. RESULTS: The patient's DAT was positive, and an IAT using her plasma was positive for cisplatin-treated RBCs. FCM using cisplatin-treated RBCs revealed that the patient's serum had higher FITC intensity than the donor's serum, indicating the existence of cisplatin-treated RBC-specific IgGs in patient's serum. CONCLUSION: Here, we report a rare case of a patient with hemolysis diagnosed using FCM to identify specific antibodies against cisplatin-treated RBCs. NIPA and immunological mechanisms may contribute to hemolysis onset during cisplatin treatment.

A single center experience for clinical evaluation of paroxysmal cold hemoglobinuria and Donath-Landsteiner testing.

BACKGROUND: Paroxysmal cold hemoglobinuria (PCH) is a rare form of autoimmune hemolytic anemia (AIHA), mainly affecting children. The diagnosis and management are challenging due to similarities to other causes for AIHA and limited availability to Donath-Landsteiner (DL) testing. STUDY DESIGN AND METHODS: In this single-center retrospective study, we aimed to characterize the clinical presentation and outcomes of PCH patients, defined as having positive Donath-Landsteiner antibodies, compared to a cohort of AIHA patients. RESULTS: DL-positive patients were observed to have higher lactate dehydrogenase levels and lower reticulocyte counts compared to DL-negative patients, although this was not statistically significant. We also observed that using steroids in DL-positive patients did not significantly impact their recovery. DISCUSSION: Our findings support the limited published data on PCH patients and further prompt larger multicenter studies to further characterize these patients so that they are more readily identified, especially in centers where DL antibody testing is not readily available.

Possible role of IL-23 inhibitor in autoimmune hemolytic anemia.

Rituximab and prednisone are commonly used treatments for autoimmune hemolytic anemia (AIHA), where the body's immune system attacks and destroys its red blood cells. However, some AIHA patients may become refractory to rituximab treatment, and this can result in continued hemolysis and persistent anemia, making it challenging for affected individuals to manage their symptoms. The underlying causes of rituximab refractoriness in AIHA patients can be complex and vary from patient to patient. Herein, we present a case of newly diagnosed warm and cold AIHA that remained in remission with an interleukin-23 inhibitor.

[Autoimmune hemolytic anemia following the third dose of the COVID-19 vaccine].

The development and exacerbation of autoimmune diseases following coronavirus disease 2019 (COVID-19) vaccination have been reported; however, there are few reports of autoimmune hemolytic anemia (AIHA). A 75-year-old woman was admitted to the emergency department 46 days after receiving her third dose of the mRNA-1273 COVID-19 vaccine because of fatigue and general weakness. Initial laboratory analyses revealed severe hemolytic anemia with positive direct and indirect Coombs test and elevation of serum indirect bilirubin and lactate dehydrogenase. The patient had no underlying disease after a close examination and was diagnosed with warm AIHA, which was thought to be associated with COVID-19 vaccination. The anemia improved daily after the administration of prednisolone. Clinicians should be aware of the possibility of AIHA being caused by COVID-19 vaccination, and monotherapy with prednisolone should be considered in cases of severe anemia.

Silvernanoparticle-induced hemolysis confounded with direct antiglobulin test-negative autoimmune hemolytic anemias diagnosis.

BACKGROUND: We describe here the first patient with recurrent hemolysis related to disinfectant containing silver nanoparticles (AgNps). METHODS: A 58-year-old chemist repeatedly experienced DAT-negative (Coombs-negative) hemolysis during the last 5 years. He was treated with a number of immunosuppressive drugs including 18 times rituximab. The attempt to treat him with cyclosporine A served only to increase the rate of hemolysis. Only by chance, we revealed that the patient regularly used a hand disinfectant containing AgNps. Serological testing was performed using standard techniques. Eryptosis was measured by binding annexin to exposed phosphatidylserine (PS) of the circulating red blood cells (RBCs). RESULTS: Antiglobulin tests remained negative, and PS exposing RBCs were detected two times during the last hemolytic episodes. Hemolysis completely disappeared following discontinuation of AgNp containing products. CONCLUSION: AgNps are increasingly being used in a large variety of products. Recently, it was reported that they induce in vitro prohemolytic and procoagulant effects via oxidative stress and eryptosis. The clinical findings imply the hemolysis was provoked by the patient's regular use of cleansing products containing AgNps. Our finding might help to explain the etiology of hemolytical disorders that may remain obscure in many cases.

Hyperhemolysis in a patient with sickle cell disease and recent SARS-CoV-2 infection, with complex auto- and alloantibody work-up, successfully treated with tocilizumab.

BACKGROUND: Hyperhemolysis syndrome (HHS) is a severe delayed hemolytic transfusion reaction seen in sickle cell disease (SCD) patients, characterized by destruction of donor and recipient RBCs. It results in a drop in hemoglobin to below pretransfusion levels and frequently reticulocytopenia. CASE REPORT: We report a case of a man in his thirties with SCD with a recent hospitalization 2 weeks prior for COVID-19. His red cell antibody history included anti-Fy(a) and warm autoantibody. At that time, he was given 2 units of RBC and discharged with a hemoglobin of 10.2 g/dl. He returned to the hospital approximately 1.5 weeks later with hemoglobin 6.0 g/dl and symptoms concerning for acute chest syndrome. Pretransfusion testing now showed 4+ pan-agglutinin in both gel-based and tube-based testing. Alloadsorption identified an anti-N and a strong cold agglutinin. Three least incompatible units were transfused to this patient over several days, with evidence of hemolysis. Further reference lab work revealed anti-Fya , anti-Fyb , anti-Lea , anti-Leb , and an anti-KN system antibody. The patient's hemoglobin nadired at 4.4 g/dl. The patient was treated with a single dose of tocilizumab, his hemoglobin stabilized, and he was discharged. DISCUSSION: We present a case of HHS proximate to recent SARS-CoV-2 infection with multiple allo and autoantibodies identified. Information on the relationship between SARS-CoV-2 infection and HHS is limited; however, it is possible that inflammation related to COVID-19 could predispose to HHS. Tocilizumab is an approved treatment for COVID-19. Additionally, tocilizumab appears to be a promising treatment option for patients with HHS.

Thromboembolic complications in autoimmune hemolytic anemia: Retrospective study.

INTRODUCTION: A small number of retrospective studies suggest AIHA to be associated with an increased risk to suffer from thromboembolic events. However, based on these studies it remains unclear whether the complement activation per is a risk factor to develop thromboembolic events in AIHA patients. The aim of this retrospective study is to investigate the incidence of thromboembolic events and the relation to complement activation in a cohort of AIHA patients. PATIENTS AND METHODS: We included 77 patients in this study with a positive DAT and hemolytic parameters or with AIHA diagnosis based on the medical report. The included patients were screened for thromboembolic events (TEE) and have been stratified in groups with and without complement activation based on the positivity for complement in the DAT. RESULTS: Of the 77 included patients, 51 (66%) had warm AIHA, 13 (17%) cold-AIHA, 5 (7%) mixed AIHA, and 8 (10%) atypical AIHA, respectively. Primary and secondary AIHA was diagnosed in 44% and 56%, respectively. Twenty patients (26%) suffered from TEE. The majority (80%) of these patients suffered from warm AIHA and 10% from cold-AIHA. Hemolysis parameters did not differ in patients with and without TEE. There was no correlation with complement activation as evidenced by a positivity for complement in the monospecific DAT with the occurrence of TEE. CONCLUSION: AIHA is associated with an increased risk of TEE. Based on these results prophylactic anticoagulation might be considered as soon as the diagnosis of AIHA is confirmed.

Life-saving transfusion in autoimmune hemolytic anemia: a case report and procedure review of the dilution method.

A woman with autoimmune hemolytic anemia (AIHA) presented in the emergency department with life-threatening anemia (hemoglobin 3 g/dL). Exaggeration of preexisting chronic anemia to severe anemia after a recent red blood cell (RBC) transfusion led to suspicion of delayed hemolytic transfusion reaction. Given the urgency for transfusion along with a stronger suspicion for coexistence of an alloantibody, the dilution method proposed by Lawrence Petz and George Garratty was used to find an RBC unit for transfusion. An alloantibody with Fyb specificity was identified, which was masked by the coexistent autoantibody. This method is based on the assumption that the titers of an alloantibody are higher than that of autoantibody. Diluting the autoantibody would reveal the alloantibody and, for this purpose, a serial doubling dilution of serum is performed. This method has an important limitation of missing any alloantibodies with titers less than that of the autoantibody. In spite of this, this method may be of use at a resource-poor setting, where trained personnel and other reagents intended for advanced immunohematology methods are unavailable.

[Thrombotic risk in autoimmune hemolytic anemia].

Autoimmune hemolytic anemia (AIHA) is a type of anemia caused by the destruction of red blood cells due to autoantibodies targeting membrane proteins. AIHA is divided into two types based on the thermal amplitude: warm AIHA (at 37°C) and cold AIHA (at <37°C). Anemia and jaundice are the major symptoms of AIHA, and in cold agglutinin disease the peripheral circulation disturbance deteriorates patients' quality of life. Cumulative evidence has revealed that both types of AIHA increase the risk of thrombosis and intravascular hemolysis appears to be the most critical factor in the pathogenesis. Complement activation plays an important role in the intravascular hemolysis of AIHA, though the coagulation and hemostatic systems and the crosstalk between these systems also contributes significantly to the pathogenesis of thrombosis. Future treatment of AIHA should be targeted at not only alleviating anemia but also reducing thrombotic risk.

[Advances in understanding the pathogenesis and treatment of autoimmune hemolytic anemia].

Autoimmune hemolytic anemia (AIHA) is caused by damaged red blood cells due to auto-antibodies targeting its membrane proteins. The heterogeneous group of diseases is divided into two types depending on the thermal amplitude of autoantibodies: warm and cold AIHA. Cold AIHA includes cold agglutin disease and paroxysmal nocturnal hemoglobinuria. AIHA is also divided into primary and secondary AIHA depending on its etiology. Recent advances in understanding the pathogenesis have revealed that AIHA brings not only anemia but also thromboembolic risk or impaired quality of life (QOL). This review describes its pathogenesis, diagnostic approach, and treatment strategies based on the latest information.

Hemolytic anemia blunts the cytokine response to transfusion of older red blood cells in mice and dogs.

BACKGROUND: Transfusion of red blood cells (RBCs) stored for longer durations induces hemolysis and inflammatory cytokine production in murine and canine models. Despite immune system activation by stored RBCs, human randomized trials suggest that fresher RBC transfusions do not improve clinical outcomes. We hypothesized that underlying recipient hemolysis may affect cytokine responses to older RBC transfusions. STUDY DESIGN AND METHODS: C57BL/6 mouse cohorts were infused with anti-TER119 antibody to induce hemolysis, rabbit anti-platelet antiserum to induce immune thrombocytopenia (ITP), or appropriate control antibodies. Two days later, mice were transfused with fresh or stored RBCs. Furthermore, in a prospective, randomized, blinded trial, 38 client-owned dogs with primary autoimmune hemolytic anemia (AIHA) and two dogs with ITP, requiring RBC transfusion, were enrolled and randomized to receive fresh (≤7 days) or old (≥21 days) stored RBC transfusions. Monocyte chemoattractant protein (MCP)-1 levels were assessed at defined times after transfusion. RESULTS: Prior immune-mediated hemolysis blunted the MCP-1 response to stored RBC transfusion in mice (361 ± 111 pg/ml vs. 6836 ± 1528 pg/ml in mice with immune hemolysis vs. ITP, respectively; mean ± SD; p < .0001). Although hemolysis markers increased after transfusion of older RBCs, the cytokine response was also muted in dogs with AIHA. No differences in morbidity or mortality were evident comparing dogs randomized to fresh or old RBCs. CONCLUSION: These data suggest that underlying hemolysis blunts inflammatory responses to old RBC transfusions. The canine data support randomized trial results suggesting a lack of clinical benefit with fresh RBC transfusions in subjects with underlying, baseline hemolysis.

Targeting the neonatal Fc receptor (FcRn) to treat autoimmune diseases and maternal-fetal immune cytopenias.

FcRn, a non-classical Fc gamma (γ) receptor (FcγR) with near ubiquitous expression, plays key roles in disease pathogenesis and progression though immunoglobulin G (IgG) transport, IgG recycling, and IgG-immune complex clearance. FcRn function can be inhibited using IgG-based and non-IgG-based antagonists, by exploiting the pH-dependent binding affinity of FcRn for the IgG Fc region. FcRn therapeutics have shown promise in murine models and human clinical trials for autoimmune diseases and maternal-fetal immune cytopenias; they appear safe, well-tolerated, and reduce circulating IgG levels. Compared to traditional therapeutics, inhibiting FcRn has fewer adverse side effects and represents a new approach that is less invasive, time-consuming, and costly.