Secondary Autoimmune Hemolytic Anemia Research Articles

Mitigation of checkpoint inhibitor–induced autoimmune hemolytic anemia through modulation of purinergic signaling

AbstractImmune checkpoint inhibitors (ICPis) have revolutionized cancer immunotherapy but also can induce autoimmune hemolytic anemia (AIHA), a severe disease with high mortality. However, the cellular and molecular mechanism(s) of AIHA secondary to ICPi therapy (ICPi-AIHA) are unclear, other than being initiated through decreased checkpoint inhibition. Herein, we report ICPi-AIHA in a novel mouse model that shows similar characteristics of known human ICPi-AIHA (eg, autoantibodies, hemolysis, and increased mortality). During ICPi-AIHA, there is the simultaneous reduction of 2 regulatory T-cell populations (FoxP3+ and Tr1 regulatory T cells) and an increase in inflammatory T helper cell 17. Moreover, a novel CD39+CD73–FoxP3–CD25– CD4+ T-cell subset (ie, CD39 single positive [CD39SP]) emerges, and early increases in CD39SP predict AIHA development; CD39 is an ectonuclease that breaks down adenosine triphosphate (ATP). Additionally, we found that boosting ATPase activity by injecting recombinant apyrase mitigates AIHA development and significant CD39SP reductions, both suggesting a functional role for CD39 and demonstrating a novel therapeutic approach. Importantly, CD39SP are detectable in multiple mouse models developing AIHA and in patients with AIHA, demonstrating applicability to idiopathic and secondary AIHA. Highlighting broader autoimmunity relevance, ICPi-treated NZB mice experienced accelerated onset and severity of lupus, including AIHA. Moreover, ICPi treatment of healthy B6 animals led to detectable CD39SP and development of autoantibodies against multiple autoantigens including those on red blood cells and platelets. Together, our findings elucidate cellular and molecular mechanisms of ICPi-AIHA, leading to novel diagnostic and therapeutic approaches with translational potential for use in humans being treated with ICPi.

A case of infectious mononucleosis caused by Epstein-Barr virus complicated by autoimmune hemolytic anemia

We represent a rare clinical case of infectious mononucleosis with hepatitis, caused by Epstein-Barr virus, complicated by rare secondary autoimmune hemolytic anemia associated with warm agglutinins in a 16-year-old patient. The disease was long-lasting, with a two-wave course of febrile fever. Signs of hepatitis with the development of anemia of moderate severity appeared during the second wave of febrile fever. The etiology of the disease was confirmed by the detection of Epstein-Barr virus DNA in blood and the detection of anti-VCA IgM antibodies to Epstein-Barr virus in the absence of anti-EBNA IgG antibodies. Hemolytic anemia was verified using markers of hemolysis (increased lactate dehydrogenase activity, decreased haptoglobin concentration), and positive results of a direct Coombs test. After successful initiation of prednisone therapy and clinical improvement, the patient was discharged from the hospital on the 24th day of disease to continue treatment on an outpatient basis (prednisone was replaced by methylprednisolone).This case demonstrates the development of a rare autoimmune complication in infectious mononucleosis caused by the Epstein-Barr virus.

Autoimmune Hemolytic Anemia Associated with Mature Ovarian Cystic Teratoma Containing Monoclonal Immunoglobulin G: A Case Report and Review of Literature

Background. Autoimmune hemolytic anemia (AIHA) associated with solid tumors such as mature cystic teratomas is rare and poorly understood. Here, we report a successfully treated case of secondary AIHA in a mature cystic teratoma containing antibodies against red blood cells. Case description. A 22-year-old woman was referred to our hospital with progressive anemia. Laboratory findings revealed hemolysis with a positive direct and indirect antiglobulin test. Imaging studies identified a left ovarian mass, suspected to be a mature cystic teratoma, which was later confirmed by histopathology after laparoscopic oophorocystectomy. The patient was treated with prednisolone, resulting in improved anemia. To examine the relationship between the tumor and AIHA, an indirect antiglobulin test was performed on the tumor contents. Stronger aggregations were observed at any concentration diluted by 10 times from 10 to 10,000 times of the tumor contents compared to the patient’s serum. Additionally, immunofixation electrophoresis of the tumor contents revealed the presence of monoclonal immunoglobulin G-κ. Conclusion. The presence of monoclonal IgG-κ in the tumor suggests intratumoral antibody production as a possible mechanism. Further research is necessary to elucidate the pathogenic relationship between such tumors and AIHA. The report also highlights the importance of considering secondary AIHA in patients with unexplained anemia and solid tumors.

Challenges in the diagnosis and management of autoimmune hemolytic anemia: A case-based approach. Experience from a tertiary care hospital in the Haryana region.

Autoimmune hemolytic anemia (AIHA) is a rare immune disorder which occurs when antibodies are directed against self red blood cells (RBCs) leading to hemolysis. AIHA is widely classified as warm autoimmune hemolytic anemia, cold agglutinin syndrome, mixed AIHA, paroxysmal cold hemoglobinuria and rarely drug induced AIHA. The pathogenesis of AIHA is complex interplay between genetic predisposition, immune dysregulation and enviornmental triggers. A direct antiglobulin test can be used to assess the immunological origin of the hemolysis in order to diagnose AIHA after identifying laboratory and clinical symptoms of hemolysis. The objective is to understand underlying mechanism in AIHAs, and usage of targeted therapies to modulate specific components of the immune response. We are hereby presenting a case series of 11 clinically suspected cases of AIHA in collaboration with their clinical features, immuno-hematological and other laboratory parameters, Flow cytometric analysis of lymphocyte subset in relevant cases, underlying etiology as well as serological subtype are also included. Majority of the patients were categorized as secondary AIHA (7/11, 63.63%). Out of 11 cases 7 were serologically subtyped as warm AIHA (7/11, 63.63%) ,2 cases were DaaT negative AIHA (2/11;18.18%), 2 cases were characterized as mixed AIHA subtype (2/11, 18.18%). Accurate subtyping of AIHA requires a systematic immunohematological approach coupled with comprehensive evaluations of clinical, hematological, and biochemical parameters.

Evaluation of hepatic toxicity in autoimmune hemolytic anemia (AIHA) and Evans syndrome patients: a single-center Egyptian study

IntroductionBenign auto-immune illnesses include Evans syndrome (ES) and auto-immune hemolytic anemia (AIHA). Despite being benign in nature, the patients’ livers are burdened by the disease’s chronicity and the accompanying problems beyond the course of treatment. An additional burden stems from HCV infection, of which a significant proportion of Egyptians are positive. The purpose of this study was to identify the hepatotoxicity risks and the variables that influence the prognosis and survival of patients with AIHA/ES. There are 126 AIHA patients in this observational study, which is retrospective. From June 2009 to March 2021, patients visited the Haematology Unit of the Oncology Centre in Egypt. One hundred and sixteen patients have available data.ResultsThere was no significant difference between primary and secondary AIHA groups as regards baseline hemoglobin (Hb), bilirubin, LDH, or reticulocyte count. Thirty-four patients (29.31%) had HCV-positive tests and 1 patient (0.9%) had HBV. There was no difference between HCV-positive and negative cases as regards mean Hb concentration, mean platelet, or immune markers (P > 0.05). AIHA patients with HCV-positive showed a significantly higher relapse rate (56%) than HCV-negative patients (32%) (P = 0.034). HCV positivity and low platelet counts at diagnosis were poor predictors for overall survival (OS) (P 0.022 and 0.04, respectively). Median OS was significantly better in patients with no viral hepatitis infection (1101 days, 95% CI 592–2068) than in patients with positive HCV infection (521, 95% CI 326–1325) (P = 0.019).ConclusionsAzathioprine is the least hepatotoxic in AIHA patients under treatment. Viral hepatitis represents a superadded damage to the liver besides AIHA concerning clinical characteristics and outcomes.

Safety and efficacy of least incompatible red cell units in autoimmune hemolytic anemia: A prospective analysis of hemoglobin increment and hemolysis after transfusion

Abstract BACKGROUND: Red blood cell (RBC) transfusion is a challenge in autoimmune hemolytic anemia (AIHA) patients due to pan reactivity and crossmatch incompatibility. Apprehensions about the safety and efficacy of least incompatible (best-matched) red cells are common among treatment providers. AIM: A primary objective was to study the effect of RBC transfusion on hemolysis parameters (hemoglobin [Hb], serum bilirubin, serum lactate dehydrogenase [LDH], and reticulocyte count) in AIHA patients. SETTINGS AND DESIGN: This was a hospital-based prospective observational study conducted on 40 AIHA patients attending the department of internal medicine from January 2020 to July 2021 who received RBC Transfusions. METHODOLOGY: Blood samples were collected for evaluating hemolysis parameters: Hb, reticulocyte count, serum bilirubin, and serum LDH before transfusion and compared with the same parameters within 12 h after transfusion. STATISTICAL ANALYSIS: Analysis was done by SPSS software Version 16. Paired t-test was used to find the effect of RBC transfusion on hemolysis parameters and independent t-test was used to compare the effect of compatible and incompatible RBC transfusions. RESULTS: The median age at presentation was 42 years with a female preponderance (67.5%). Majority of the patients belong to warm AIHA (73%) and Secondary AIHA (60%). Compatible RBC units could be provided to 57% of cases and 43% were transfused with the least incompatible units. The mean pretransfusion Hb in AIHA was 4.3 mg/dl and showed a statistically significant increase after transfusion (P < 0.001). A significant difference between reticulocyte levels of compatible and incompatible transfusions was noted with a P = 0.025. No statistically significant difference noticed in Hb, serum LDH, serum bilirubin levels between compatible and incompatible RBC transfusions. CONCLUSION: RBC transfusions in AIHA patients provide Hb increment similar to other anemic patients. RBC transfusions should not be denied in AIHA patients in view of hemolysis and best-matched units also may be transfused in indicated cases.

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.

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.

Clinical and immunohematological characterization of autoimmune hemolytic anemia in children

Autoimmune Hemolytic Anemia (AIHA) in childhood is uncommon and estimated to be three per million annually under 18 years of age. Detailed immunohematological and clinical characterizations are essential for correct diagnosis of the disease and its management. In this study we described AIHA in children with regards to patient demography, underlying etiology, disease classification, antibody characterization, clinical features, degree of in vivo hemolysis and transfusion management. The prospective observational study was conducted over a period of 6 years and included 29 children with newly diagnosed AIHA. Patient details were obtained from the hospital information system and patient treatment file. The median age of the children was 12 years with a female preponderance. Secondary AIHA was observed in 62.1% patients. The mean hemoglobin and reticulocyte were 7.1 gm/dL and 8.8 percentages respectively. The median polyspecific direct antiglobulin test (DAT) grading was 3+. Red cell bound multiple autoantibodies were found in 27.6% children. Free serum autoantibodies were present in 62.1% patients. Twenty six of the 42 units transfused were “best match” or “least incompatible”. Follow-up of 21 children showed clinical and laboratory improvement with DAT still positive at the end of 9 months. AIHA in childhood requires advanced and efficient clinical, immunohematological and transfusion support. Detailed characterization of AIHA is important, as they determine degree of in vivo hemolysis, disease severity, serological incompatibility and necessity of blood transfusion. Although blood transfusion in AIHA is a challenge but it should not be withheld in critically ill patients.

Role of direct antiglobulin test in assessing the severity of extravascular hemolysis in autoimmune hemolytic anemia – analysis from a cross-sectional study

Background: Autoimmune hemolytic anemia (AIHA) is an immune hemolytic disease characterized by hemolysis and anemia which results from increased red cell destruction due to auto antibodies directed against self-antigens on red cells. Clinical characteristics and potential associated hemolysis in AIHA can greatly depend on the serological characteristics. Aims and Objectives: This study was done to find out the association of Grade of polyspecific Direct Antiglobulin test (DAT), complement involvement and immunoglobulin G (IgG) subclass with severity of hemolysis in an AIHA patients. Materials and Methods: This was a cross-sectional study conducted for a period of 18 months from March 1, 2012, to August 31, 2013. Fifty consecutive AIHA patients diagnosed by a positive DAT in EDTA anticoagulated blood samples using poly specific anti human globulin reagent were followed up and results of various immunohematological tests such as polyspecific and monospecific DAT, IgG subtyping, and thermal amplitude were performed. Hematological and biochemical parameters such as hemoglobin, percentage of reticulocyte, total serum bilirubin, and serum lactate dehydrogenase also were recorded. Data were analyzed using SPSS v17. Results: Majority of patients were belonging to 31–40 year age group and there was a remarkable female predilection. Secondary AIHA was more common (56%) than primary. SLE was identified as the most common underlying disorder in secondary AIHA. Majority (46%) were Grade 4 DAT positive. Predominant autoantibody identified was IgG (52%). Of the total IgG positive cases, IgG1 was the predominant subclass. C3d alone was detected in 18% of cases and C3d and IgG together in 30%. About 48% of our patients were of warm type, 32% mixed type, and 20% cold type. About 80% of the study population were treated with steroids alone. A small percentage of cases (16%) needed immunosuppressant in addition to steroids and still a smaller percentage (4%) needed splenectomy. Higher grades of DAT positivity were associated with more severe degree of anemia and hyperbilirubinemia. The study also demonstrated a positive correlation between DAT grade and severity of hemolysis. Conclusion: AIHA patients in this study were predominantly of Warm AIHA with more of IgG1 involvement. A significant association is found between higher grades of DAT results and severity of anemia and jaundice in this study group. A positive correlation exists between grades of DCT and hemolysis as well.

Transfusion Challenges and Use of Best Match Blood Transfusion in Autoimmune Hemolytic Anemia Patients

Background and Objectives: In autoimmune hemolytic anemia (AIHA) patients, there is decreased survival of red blood cells (RBCs) because of increased destruction by patients' autoantibodies. Due to decreased survival of RBCs, there is an increase in erythropoiesis and other biochemical parameters of hemolysis. One of the vital tests in AIHA is direct Coombs test (DCT). In this study, we share our experience on the difficulties faced by us during the compatibility testing and providing transfusion support to these patients. Methods: This is a retrospective study done in the department of transfusion medicine in a tertiary care hospital of South India. Patients from January 2020 to March 2021 with the diagnosis of AIHA requiring transfusion were included in this study. A total of 136 patients with positive DCT with AIHA diagnosis requiring transfusion support were included in our study. Results: Out of 136 cases, 58% (n=79) of patients had incompatibility during cross matching while in 42% (n=57) had cross matched compatible unit. In all incompatible cases best match blood was transfused. Most transfusions were done for patients with DCT Grade 4+. Out of 45 patients with mixed AIHA, 40 (88.8%) patients required a transfusion (P < 0.05). Of that 104 patients with transfusion support, 66 (63%) were with primary AIHA and 38 (36.04%) with secondary AIHA. Conclusion: It is tough and challenging to get compatible units in AIHA patients. Best-matched blood is useful when transfusion becomes essential during life-threatening anemia.

Immune Hemolytic Anemia

The diagnosis of autoimmune haemolytic anaemia (AIHA) is a challenge for both the immune-haematology laboratory and the clinician as the laboratory investigation can be troublesome and often requires extensive time-consuming serological testing, especially when a blood transfusion is needed. Frequently, there is a need to start therapy rapidly. Autoantibodies directed to epitopes on red blood cell (RBC) consisting in sugar and/or protein structures are crucial in the pathogenesis of AIHA. The isotype is important for the clinical significance of an autoantibody. Frequently, patients are icteric and suffer from clinical signs of anaemia, such as pallor, fatigue, shortness of breath and palpitations, on examination hepatosplenomegaly can be present. If there is no vital indication for a transfusion it is prudent to wait for the results of the immune-haematological tests and the ensuing transfusion advice based on this. Focus of treatment should be stoppage of hemolysis or at least be attenuated via an inhibition of autoantibody production and/or inhibition of premature RBC destruction. Successful treatment of secondary AIHA is only possible when the underlying disease is treated.

Survival in autoimmune hemolytic anemia remains poor, results from a nationwide cohort with 37 years of follow‐up

IntroductionAutoimmune hemolytic anemia (AIHA) is considered a chronic disease, with an overall good prognosis. However, recent reports indicate pre‐mature mortality. Causes of death have not been evaluated previously.MethodsIn a nationwide setting, we identified all patients with warm type AIHA or cold agglutinin disease (CAD), and age–sex‐matched comparators from Denmark, 1980–2016. We estimated overall survival and cause‐specific mortality from anemia, infection, cardiovascular causes, hematological or solid cancer, bleeding, or other causes, using cumulative incidence proportions.ResultsWe identified 1460 patients with primary AIHA, 1078 with secondary AIHA, 112 with CAD, and 130 801 comparators. One‐year survival and median survival were, 82.7% and 9.8 years for primary AIHA, 69.1% and 3.3 years for secondary AIHA, and 85.5% and 8.8 years for CAD. Prognosis was comparable to the general population only in patients with primary AIHA below 30 years. In all other age and subgroups, the difference was considerable. Cumulated cause‐specific mortality at 1 year was increased among patients versus comparators.DiscussionAll groups of autoimmune hemolytic anemia are associated with increased overall and cause‐specific mortality compared to the general population. This probably reflects unmet needs in both treatment and follow‐up programs.

Clinical and surgical outcomes of splenectomy for autoimmune hemolytic anemia.

We investigated short and long-term remission rates after splenectomy in patients with primary and secondary autoimmune hemolytic anemia (AIHA). All adults who underwent splenectomy for primary or secondary AIHA at a single center (2004-2018) were retrospectively reviewed. Short-term response was determined at 30-day postoperatively and long-term at one year. Complete response was defined as hemoglobin > 10g/dL without hemolysis, transfusions, or need for additional medical therapy for > 6months. Short-term complete response was attained in 22 of 36 patients (61%), partial response in 3 (8%), no response in 11 (31%). The response rate at 1year was complete in 14/36 (39%), partial in 14 (39%), and 8 non-response (22%). At last available follow-up (median 33.1months (IQR 19-59), 16/37 patients had experienced a complete response (43%), 14 partial response (38%), 7 non-response (19%). 80% of partial responders with primary AIHA required maintenance therapy compared to 100% with secondary AIHA. Splenectomy is associated with short- and long-term improvement in anemia and hemolysis in the majority of patients with AIHA. Immunosuppressants remain important supplemental therapy.

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.

A New Murine Model of Primary Autoimmune Hemolytic Anemia (AIHA).

Loss of humoral tolerance to red blood cells (RBCs) can lead to autoimmune hemolytic anemia (AIHA), a severe, and sometimes fatal disease. Patients with AIHA present with pallor, fatigue, decreased hematocrit, and splenomegaly. While secondary AIHA is associated with lymphoproliferative disorders, infections, and more recently, as an adverse event secondary to cancer immunotherapy, the etiology of primary AIHA is unknown. Several therapeutic strategies are available; however, there are currently no licensed treatments for AIHA and few therapeutics offer treatment-free durable remission. Moreover, supportive care with RBC transfusions can be challenging as most autoantibodies are directed against ubiquitous RBC antigens; thus, virtually all RBC donor units are incompatible. Given the severity of AIHA and the lack of treatment options, understanding the cellular and molecular mechanisms that facilitate the breakdown in tolerance would provide insight into new therapeutics. Herein, we report a new murine model of primary AIHA that reflects the biology observed in patients with primary AIHA. Production of anti-erythrocyte autoantibodies correlated with sex and age, and led to RBC antigen modulation, complement fixation, and anemia, as determined by decreased hematocrit and hemoglobin values and increased reticulocytes in peripheral blood. Moreover, autoantibody-producing animals developed splenomegaly, with altered splenic architecture characterized by expanded white pulp areas and nearly diminished red pulp areas. Additional analysis suggested that compensatory extramedullary erythropoiesis occurred as there were increased frequencies of RBC progenitors detectable in the spleen. No significant correlations between AIHA onset and inflammatory status or microbiome were observed. To our knowledge, this is the first report of a murine model that replicates observations made in humans with idiopathic AIHA. Thus, this is a tractable murine model of AIHA that can serve as a platform to identify key cellular and molecular pathways that are compromised, thereby leading to autoantibody formation, as well as testing new therapeutics and management strategies.

The spectrum of underlying diseases in children with autoimmune hemolytic anemia

Aim: Autoimmune hemolytic anemia (AIHA) is characterized by the production of antibodies directed against red blood cells. We aimed to describe the clinical presentation, hematologic and biochemical profiles, treatment modalities, underlying diseases and outcomes in children suffering from AIHA. 
 Material and Method: In a retrospectively manner, we consecutively recrutied 62 children (aged 1 month-18 years) with AIHA who had been followed in Erciyes University Child Hospital between January, 2000 and November, 2017. 
 Results: The mean age at time of diagnosis was 61.9±51.9 months (range:1-192) in 62 children including 28 girls and 34 boys. The most common complaints included fatigue and fever while the most common findings were jaundice and hepatosplenomegaly. In 22 children (35.4%), there was a comorbid, active, non-specific infection (upper respiratory tract infection, lower respiratory tract infection, diarrhea, urinary tract infection). At time of diagnosis, mean hemoglobin (Hb) level was 6.9±2.5 g/dL (range: 5-9). The glucocorticoid therapy was given in majority of the patients while no medical treatment was given to 4 patients. Of the patients with primary AIHA, 6 patients were unresponsive to the treatment while one patient responded partially. It was found that there were underlying risk factors in 36 patients with secondary AIHA, as immunodeficiency and autoimmune disorders being the most common risk factors. 
 Conclusion: The immunodeficiencies were highly prevalent in children included. By advance of whole exome sequencing technology, we believe that primary immunodeficiencies was the most common underlying disease in our study detected quite high in presented children.

Clinical Profile and Outcome of Childhood Autoimmune Hemolytic Anemia: A Single Center Study

ObjectiveTo analyze clinical and laboratory parameters, and treatment outcomes of children with autoimmune hemolytic anemia (AIHA).MethodsRetrospective analysis of 50 children aged 0–18 years. Monospecific direct antiglobulin test (DAT) and investigations for secondary causes were performed. Disease status was categorized based on Cerevance criteria.ResultsMedian (range) age at diagnosis was 36 (1.5–204) months. AIHA was categorized as cold (IgM+,C3+/cold agglutinin+) (35%), warm (IgG+ with/without C3+) (28%), mixed (IgG+, IgM+, C3+) (15%) and paroxysmal cold hemoglobinuria (4%). Primary AIHA accounted for 64% cases. Treatment modalities included steroid (66%), intravenous immunoglobulin (IVIg) (4%), steroid+IVIg (4%), and steroid+rituximab (4%). Treatment duration was longer for secondary AIHA than primary (11 vs 6.6 months, P<0.02) and in patients needing polytherapy than steroids only (13.3 vs 7.5 months, P<0.006). During median (range) follow-up period of 73 (1–150) months, 29 (58%) remained in continuous complete remission, 16 (32%) remained in complete remission.ConclusionInfants with AIHA have a more severe presentation. Monospecific DAT and a thorough search for an underlying cause help optimize therapy in most patients of AIHA.

Severe haemolytic anaemia in COVID 19- A rare manifestation.

Sir, The novel severe acute respiratory syndrome-corona virus 2 (SARS-CoV-2) affects various organ systems including the cardiovascular, gastrointestinal and neurological systems.[1] Autoimmune haemolytic anaemia (AIHA) is a rare immune disorder in which antibodies are produced against body's own red cells. Association of AIHA with coronavirus disease (COVID)-19 has been rarely reported. A 42-year-old female patient presented with fatigue, headache and bleeding per rectum since 3 days; she had no history of fever or upper respiratory tract infection and normal oxygen saturation. On clinical examination, she was pale and icteric and had healing fissure in ano with no active bleeding. On day two, patient complained of severe breathlessness, peripheral oxygen saturation (SpO2) 85% with hypotension and patient was shifted to intensive care unit (ICU) for further management. The oxygen was administered with facemask at 10 l/min and norepinephrine infusion started at 0.5-1 μg/kg/min. The chest radiogram and echocardiogram did not show any abnormality. Computed tomography (CT) chest [Figure 1] revealed a CORADS score of 6 and the reverse transcription polymerase chain reaction (RT PCR) assay detected the presence of SARS-CoV-2 on day three of admission. On investigation, her haemoglobin level was 3 g% and peripheral blood smear showed predominantly macrocytic hypochromic cells with a few microcytes, anisocytosis, reticulocytosis and neutrophilia. Malignant diseases, such as leukaemia and lymphoma, were ruled out as the peripheral smear did not show abnormal cells of haematological origin. Autoimmune diseases, such as systemic lupus erythematosus, were also ruled out. There was no history of medication intake (non-steroidal anti-inflammatory drugs or cephalosporins) or blood transfusion in the past known to cause drug-induced AIHA. Arterial blood gas analysis was not required as hypoxaemia was anticipated due to severe anaemia. Considering the severe anaemia and increasing breathlessness, a decision to transfuse packed red cells was taken. Her cell grouping was AB Rh D positive, whereas her serum grouping was of O group with autocontrol positive drawing attention to the pathology (O Rh D positive per previous records). Cross-matching with both AB Rh D positive and O Rh D positive packed cells were incompatible, concomitantly direct antiglobulin and indirect antiglobulin tests were also positive. Her blood also showed autoagglutination (titres <1:64), which was reactive at 37°C and with antihuman globulin phase; hence a provisional diagnosis of mixed AIHA was established secondary to infection. Intravenous methylprednisolone 30 mg/kg for 3 days, 20 mg/kg for next 3 days, and 5 mg/kg for next 4 days was started till irradiated or compatible blood was arranged as per British Society of Haematology guidelines.[2] Oral prednisolone 1 mg/kg was continued for 2 weeks and gradually tapered. The patient showed marked improvement in the next 24 h [Table 1], could be managed without any blood transfusion and ionotropic supports could be discontinued. A diagnosis of secondary AIHA triggered by COVID-19 was ascertained by exclusion as the patient had no other suggestive history.Figure 1: (a) Opacification in the right peripheral lung fields and (b) Opacifications in the bilateral posterior aspect of the lung fields due to COVID-19Table 1: Serial measurement of complete blood picture taken before and after initiation of methylprednisolone therapy for a period of 12 days‡Autoimmune haemolytic anaemia in COVID-19 has been reported in nine cases among which five had malignancy and one had congenital thrombocytopenia.[3] ANK-1 shares an immunogenic antigenic epitope (amino acids LLLQY), present on red cells with 100% identity with the SARS-CoV-2 surface glycoprotein named spike protein, which creates a potential immunological cross-reactivity between ANK-1 and spike protein, contributing to AIHA in patients with COVID-19.[4] Corticosteroids represent the first line of treatment for warm antibody type AIHA and reduce haemolysis and cytokine storm.[5] This case presents a unique scenario of acute anaemia with COVID-19, which was managed conservatively with steroids and no immunosuppressants or plasma therapy or blood transfusion was required. We wish to highlight that the novel SARS-CoV-2 can present with covert symptoms affecting the haematological system. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the legal guardian has given his consent for images and other clinical information to be reported in the journal. The guardian understands that names and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed. Financial Support and Sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Early-onset antibiotic-induced autoimmune hemolytic anemia

Drug-induced immune hemolytic anemia (DIIHA) is a rare adverse reaction that causes secondary autoimmune hemolytic anemia in susceptible patients. Drug-induced antibodies and nonimmunological protein absorption are the known mechanisms associated with DIIHA. The two most common reported antibiotics to cause drug dependent antibodies are cephalosporin and penicillin. The author reports two rare cases of DIIHA. The first case is a middle-aged woman clinically diagnosed with community-acquired pneumonia, which develops hemolytic anemia secondary to ceftriaxone. The second case is an elderly gentleman who developed DIIHA secondary to piperacillin–tazobactam that started managing gastrostomy site infection. Both patients had hypoxemia and shortness of breath secondary to drop in hemoglobin, but the outcome was uneventful. Antibiotic-induced hemolytic anemia can develop as early as 2 days after starting the antibiotic. Therefore, early diagnosis and discontinuation of the offending agent can prevent poor prognosis.