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Thalassaemia, a common inherited blood disorder, involves defective globin production leading to premature erythrocyte destruction. Autoimmune haemolytic anaemia (AIHA), a rare complication in thalassaemia, is characterised by autoantibody production against erythrocytes. We present a case of a 7-month-old boy diagnosed with β-thalassaemia major (BTM), complicated by AIHA six weeks after initiating blood transfusions. Despite daily transfusions and oral Prednisolone, the haemoglobin (Hb) level dropped to a life-threatening level (2.5g/dl). High-dose IV Methylprednisolone and Rituximab were administered, resulting in Hb improvement to 11.9 g/dL. AIHA resolution was indicated by negative C3d and reduced IgG on repeated testing. Recognition of AIHA in BTM is vital for effective management, including immunosuppressive therapy, leucodepleted transfusions, and potential splenectomy or haematopoietic stem cell transplant. Early intervention is crucial to reduce the mortality associated with AIHA in children. [ABSTRACT FROM AUTHOR]

Objective: Infantile giant cell hepatitis with autoimmune haemolytic anaemia (GCH-AHA) is a rare disease characterised by giant cell and autoimmune haemolysis. The pathogenic mechanisms involve several factors, including genetic and immunological components, particularly those related to the lectin pathway of the complement system. In this study, we aimed to identify possible germline variations in patients with GCH-AHA. Material and Method: Whole-exome sequencing (WES) was performed on a 6-month-old boy who was diagnosed with GCHAHA. An in-house data analysis pipeline was applied to determine familial segregation using Sanger sequencing. ELISA was used for MASP2 protein detection. Result: WES revealed a likely pathogenic heterozygous missense variant (p.(Cys618Tyr)) in the mannose-binding lectin (MBL)-associated serine protease-2 (MASP-2) gene. The MASP2 variant identified in the serine protease domain was predicted to disrupt disulphide bonds. In vitro assays showed decreased MASP2 levels in the patient and mother compared with controls, supporting the potential pathogenicity of the variant. Objective: Infantile giant cell hepatitis with autoimmune haemolytic anaemia (GCH-AHA) is a rare disease characterised by giant cell and autoimmune haemolysis. The pathogenic mechanisms involve several factors, including genetic and immunological components, particularly those related to the lectin pathway of the complement system. In this study, we aimed to identify possible germline variations in patients with GCH-AHA. Material and Method: Whole-exome sequencing (WES) was performed on a 6-month-old boy who was diagnosed with GCHAHA. An in-house data analysis pipeline was applied to determine familial segregation using Sanger sequencing. ELISA was used for MASP2 protein detection. Result: WES revealed a likely pathogenic heterozygous missense variant (p.(Cys618Tyr)) in the mannose-binding lectin (MBL)-associated serine protease-2 (MASP-2) gene. The MASP2 variant identified in the serine protease domain was predicted to disrupt disulphide bonds. In vitro assays showed decreased MASP2 levels in the patient and mother compared with controls, supporting the potential pathogenicity of the variant. [ABSTRACT FROM AUTHOR]

Autoimmune haemolytic anaemia (AIHA) is characterized by an increased destruction of red blood cells due to immune dysfunction and auto‐antibody production. Clinical manifestations are mainly related to anaemia, which can become life‐threatening in case of acute haemolysis. Aiming at counterbalancing severe anaemia, supportive treatments for these patients frequently include transfusions. Unfortunately, free serum auto‐antibodies greatly interfere in pre‐transfusion testing, and the identification of compatible red blood cell units for AIHA patients can be challenging or even impossible. Problems faced in pre‐transfusion testing often lead to delay or abandonment of transfusions for AIHA patients. In this review, we discuss publications concerning global transfusion management in AIHA, with a focus on pre‐transfusion testing, and practical clues to manage the selection of transfusion units for these patients. Depending on the degree of transfusion emergency, we propose an algorithm for the selection and laboratory testing of units to be transfused to AIHA patients. [ABSTRACT FROM AUTHOR]

BackgroundEosinophilic granulomatosis with polyangiitis (EGPA) is an extremely rare type of vasculitis characterized by inflammation within small blood vessels or tissues that may cause damage to the lungs, heart, kidneys, and other organs. Here, we present a rare case of EGPA with cardiac involvement that presented with acute heart failure.Clinical findingsA 44-year-old woman with a history of bronchial asthma and sinusitis presented with fever, shortness of breath, fatigue, unintentional weight loss, and polyarthritis. Physical examination revealed bilateral basal crepitation and mononeuritis multiplex.DiagnosisThe peripheral blood smear revealed red blood cells of different sizes and shapes (dimorphic features), more eosinophils, low hemoglobin, and higher lactate dehydrogenase (LDH) levels. Cardiac magnetic resonance imaging (CMR) revealed global hypokinesia and features suggestive of myocarditis. Echocardiography showed a low ejection fraction of 25%. Thus, the patient diagnosed with EPGA and myocarditis presented with acute heart failure.InterventionsThe patient was administered high-dose corticosteroids (intravenous bolus methylprednisolone 500 mg for three days, followed by 1 mg/kg of prednisolone) and cyclophosphamide 750 mg intravenously.OutcomeAfter one months, the patient showed a marked improvement in clinical and laboratory parameters. The ejection fraction improved to 30%–40%, the eosinophil count returned to normal, and the haemolytic anaemia resolved. The patient was sent home and shifted to mycophenolate mofetil 1 g twice a day as maintenance therapy.ConclusionPatients with EGPA have a higher morbidity and mortality rate when they have cardiac involvement. The pathophysiological mechanism of cardiac involvement in EGPA warrants consideration of immunosuppressive therapy in addition to standard heart failure treatment.

Summary: Currently, there is no effective treatment for refractory/relapsed (R/R) autoimmune haemolytic anaemia (AIHA), associated with poor quality of life. Bruton tyrosine kinase inhibitors have begun to be used in some autoimmune diseases. We initiated the clinical trial of orelabrutinib treatment on R/R AIHA/Evans Syndrome, which is in progress. The preliminary results showed that nine of the 12 enrolled patients responded to orelabrutinib treatment. Here, we reported three cases who have completed the treatment and were followed up for 6 months, achieving complete or partial remission. Orelabrutinib is expected to become a new second‐line treatment for R/R AIHA/Evans syndrome. [ABSTRACT FROM AUTHOR]

Summary: Background: Cold agglutinin disease (CAD) is a rare autoimmune haemolytic anaemia mediated by the classical complement pathway (CP). Sutimlimab selectively targets complement C1s inhibiting classical CP activation. In CADENZA Part A (26-weeks), a placebo-controlled study in patients without recent transfusion history, sutimlimab reduced haemolysis, anaemia, and fatigue, and was generally well tolerated. Methods: The CADENZA study (NCT03347422) started in March 2018 (Part A) and completed in December 2021 (Part B). All patients in Part B were eligible to receive sutimlimab for up to 1 year after the last patient completed Part A. Efficacy and safety was assessed throughout Part B, until the last on-treatment visit with available assessment (LV), and after a 9-week washout. Findings: In total, 32/39 patients completed Part B; median treatment duration: 99 weeks. Similar sustained improvements in haemolysis, anaemia, and quality of life were observed in patients switching to sutimlimab and those continuing sutimlimab. Mean LV values for the combined group (ie, placebo-to-sutimlimab group and sutimlimab-to-sutimlimab group) improved from baseline for haemoglobin (≥11.0 g/dL on-treatment vs 9.3 g/dL at baseline), bilirubin (≤20.0 μmol/L on-treatment vs 35.0 μmol/L at baseline), and FACIT-Fatigue scores. Following a 9-week washout, inhibition of CP activity was reversed, and haemolytic markers approached baseline levels. Overall, sutimlimab was generally well tolerated throughout the study. No patients developed systemic lupus erythematosus or meningococcal infections. During the 9-week washout, most adverse events could be attributed to recurrence of underlying CAD. Interpretation: The CADENZA Part B results support the sustained efficacy and safety of sutimlimab for treatment of CAD; however, upon discontinuation disease activity reoccurs. Funding: Sanofi.

Some patients with warm autoimmune haemolytic anaemia (wAIHA) or Evans syndrome (ES) have no response to glucocorticoid or relapse. Recent studies found that sirolimus was effective in autoimmune cytopenia with a low relapse rate. Data from patients with refractory/relapsed wAIHA and ES in Peking Union Medical College Hospital from July 2016 to May 2022 who had been treated with sirolimus for at least 6 months and followed up for at least 12 months were collected retrospectively. Baseline and follow-up clinical data were recorded and the rate of complete response (CR), partial response (PR) at different time points, adverse events, relapse, outcomes, and factors that may affect the efficacy and relapse were analyzed. There were 44 patients enrolled, with 9 (20.5%) males and a median age of 44 (range: 18–86) years. 37 (84.1%) patients were diagnosed as wAIHA, and 7 (15.9%) as ES. Patients were treated with sirolimus for a median of 23 (range: 6–80) months and followed up for a median of 25 (range: 12–80) months. 35 (79.5%) patients responded to sirolimus, and 25 (56.8%) patients achieved an optimal response of CR. Mucositis (11.4%), infection (9.1%), and alanine aminotransferase elevation (9.1%) were the most common adverse events. 5/35 patients (14.3%) relapsed at a median of 19 (range: 15–50) months. Patients with a higher sirolimus plasma trough concentration had a higher overall response (OR) and CR rate (p = 0.009, 0.011, respectively). At the time of enrolment, patients were divided into two subgroups that relapsed or refractory to glucocorticoid, and the former had poorer relapse-free survival (p = 0.032) than the other group. Sirolimus is effective for patients with primary refractory/relapsed wAIHA and ES, with a low relapse rate and mild side effects. Patients with a higher sirolimus plasma trough concentration had a higher OR and CR rate, and patients who relapsed to glucocorticoid treatment had poorer relapse-free survival than those who were refractory. [ABSTRACT FROM AUTHOR]

AbstractBackground Some patients with warm autoimmune haemolytic anaemia (wAIHA) or Evans syndrome (ES) have no response to glucocorticoid or relapse. Recent studies found that sirolimus was effective in autoimmune cytopenia with a low relapse rate.Methods Data from patients with refractory/relapsed wAIHA and ES in Peking Union Medical College Hospital from July 2016 to May 2022 who had been treated with sirolimus for at least 6 months and followed up for at least 12 months were collected retrospectively. Baseline and follow-up clinical data were recorded and the rate of complete response (CR), partial response (PR) at different time points, adverse events, relapse, outcomes, and factors that may affect the efficacy and relapse were analyzed.Results There were 44 patients enrolled, with 9 (20.5%) males and a median age of 44 (range: 18–86) years. 37 (84.1%) patients were diagnosed as wAIHA, and 7 (15.9%) as ES. Patients were treated with sirolimus for a median of 23 (range: 6–80) months and followed up for a median of 25 (range: 12–80) months. 35 (79.5%) patients responded to sirolimus, and 25 (56.8%) patients achieved an optimal response of CR. Mucositis (11.4%), infection (9.1%), and alanine aminotransferase elevation (9.1%) were the most common adverse events. 5/35 patients (14.3%) relapsed at a median of 19 (range: 15–50) months. Patients with a higher sirolimus plasma trough concentration had a higher overall response (OR) and CR rate (p = 0.009, 0.011, respectively). At the time of enrolment, patients were divided into two subgroups that relapsed or refractory to glucocorticoid, and the former had poorer relapse-free survival (p = 0.032) than the other group.Conclusion Sirolimus is effective for patients with primary refractory/relapsed wAIHA and ES, with a low relapse rate and mild side effects. Patients with a higher sirolimus plasma trough concentration had a higher OR and CR rate, and patients who relapsed to glucocorticoid treatment had poorer relapse-free survival than those who were refractory.

We present the case of a 70-year-old woman presenting with nausea, diarrhoea and a generalised rash. Initial blood tests revealed obstructive deranged liver function tests and low haemoglobin. A haemolysis screen revealed raised reticulocytes, low haptoglobin and a positive direct antiglobulin test. 6 days into her admission, she developed lower limb weakness and loss of sensation. MRI spine showed no significant findings. Cerebrospinal fluid showed raised white blood cell count and raised protein. Nerve conduction studies were normal. The clinical picture was in keeping with transverse myelitis. Autoimmune and viral screens were negative except for a single result which provided the unifying diagnosis: Epstein--Barr virus (EBV). She responded to high dose intravenous corticosteroids and her rehabilitation is ongoing. EBV should be considered even in the older population. [ABSTRACT FROM AUTHOR]

During the ongoing coronavirus disease 2019 (COVID-19) pandemic, a number of autoimmune diseases have been found to be associated with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection, with thrombocytopenia being the most common. The present study describes the case of a female patient who tested positive for SARS-CoV-2 infection from samples from two nasopharyngeal swabs examined using RT-PCR; she was admitted to hospital for severe anaemia. The woman also tested positive to direct antiglobulin test (DAT). In addition, the literature was reviewed for cases of anaemia concomitant to COVID-19 and only cases of autoimmune haemolytic anaemia (AIHA) with positive DAT were considered. A total of 38 cases of AIHA concomitant to COVID-19 were identified. In the cases reported in the literature, both warm AIHA and cold agglutinin disease were observed, with a marked prevalence of CAD. The majority of the cases identified in the literature, including the patient described herein, have had a full recovery from both COVID-19 and AIHA; however, as some of the patients visited the hospital for observation when their condition was already at an advanced and severe stage, effective therapy could not be administered and they consequently succumbed. On the whole, as autoimmune anaemia may be a consequence of SARS-CoV-2 infection, it should perhaps be considered among the haematological autoimmune disorders secondary to COVID-19, along with thrombocytopenia. [ABSTRACT FROM AUTHOR]

Cold agglutinin disease (CAD) is a rare cold autoimmune haemolytic anaemia (cAIHA) caused by IgM antibodies recognizing I antigens on erythrocytes. cAIHA is now mainly classified into two types: primary CAD and cold agglutinin syndrome (CAS). CAS develops in association with the underlying disease, which is most commonly malignant lymphoma. Recent studies have identified gene mutations in CARD11 and KMT2D in a high proportion of patients with CAD, which has led to recognition of CAD as an indolent lymphoproliferative disorder. We herein report a case of cAIHA without lymphocytosis or lymphadenopathy in whom bone marrow was infiltrated by a small population of clonal lymphocytes (6.8%) expressing cell surface markers consistent with chronic lymphocytic leukaemia (CLL). Whole-exome sequencing of bone marrow mononuclear cells revealed mutations in the CARD11 and KMT2D genes. This patient also had somatic hypermutation with overrepresentation of IGHV4-34, which is prevalent in CLL harbouring the KMT2D mutation. These observations suggest that CAS caused by early-phase CLL could be misinterpreted as primary CAD. [ABSTRACT FROM AUTHOR]

Summary: Autoimmune haemolytic anaemia (AIHA) and immune thrombocytopenia (ITP) are two uncommon haematologic autoimmune conditions that can rarely arise secondary to vaccination. Prior studies using the US Centers for Disease Control's (CDC) Vaccine Adverse Event Reporting System (VAERS) have demonstrated this infrequency, but contemporary data as well as comparison with current information regarding SARS‐CoV‐2 vaccination has not been assessed. In this study, we reviewed VAERS database reports from 1990 to 2022 to characterize the incidence and clinical and laboratory findings of non‐SARS‐CoV‐2‐associated AIHA and ITP and SARS‐CoV‐2 vaccine‐associated AIHA and ITP. We discovered a total of 863 AIHA and ITP reports following vaccination with 15 non‐SARS‐CoV‐2 and four SARS‐CoV‐2 vaccines submitted to the CDC VAERS database. AIHA and ITP reporting was low for both groups, with a large proportion excluded due to a lack of clinical details. ITP was reported the most frequently in both groups and was significantly more common with measles–mumps–rubella (MMR) vaccination (p < 0.001) in the non‐SARS‐CoV‐2 group. AIHA and ITP cases were higher in the SARS‐CoV‐2 vaccine group, though ultimately still very infrequent. Autoimmune haematologic disease is vanishingly rare after immunization and rates are lower than in the general population according to passive reporting. [ABSTRACT FROM AUTHOR]

Introduction: Mixed warm and cold autoimmune haemolytic anaemia (AIHA) secondary to COVID-19 is rarely reported. Case Report: We present a case of a 65-year-old Malay lady with no known medical illness, who was admitted for COVID-19 category 3 and mixed warm and cold AIHA. She presented with lethargy, productive cough and on and off fever. Blood investigations showed severe anaemia with spurious macrocytosis, increased lactate dehydrogenase (LDH) and total bilirubin with indirect bilirubin predominance. On full blood picture (FBP), there was normocytic normochromic anaemia with reticulocytosis, red blood cells clumping and NRBC's were seen. Both anti-IgG and anti-C3d were positive for monospecific Coombs test. For indirect Coombs test, auto-IgG and cold agglutinin were detected. Discussion: These findings were consistent with mixed warm and cold AIHA. She was treated with intravenous methylprednisolone, before being changed to high dose oral prednisolone. A total of 3 units packed cells were transfused. [ABSTRACT FROM AUTHOR]

Autoimmune haemolytic anaemia (AIHA) is an acquired disorder in which antibodies are produced against self-erythrocyte antigens. We distinguish those produced by cold antibodies (IgM), which may be associated with lymphoproliferative syndromes, infectious diseases, other autoimmune phenomena, as well as drugs or solid tumours. We report a case of AIHA due to cold antibodies as a paraneoplastic syndrome (PNS) in a patient with metastatic renal carcinoma. A 67-year-old man with newly diagnosed stage IV renal carcinoma with hepatic, bone, and lymph node involvement was consulted for abdominal pain. Laboratory tests showed grade 4 anaemia (4.5 g/dL), with positive direct Coombs’ test C3bC3d and agglutinated red blood cells in the blood smear. AIHA by cold antibodies was labelled as PNS in the context of the patient; therefore, blood transfusion as well as treatment of the underlying disease with tyrosine kinase inhibitors (sunitinib) were initiated, with subsequent clinical and analytical improvement. AIHA due to cold antibodies is a well-known PNS in lymphoproliferative disorders, although association with solid tumours, such as Kaposi’s sarcoma and non-small-cell lung cancer have also been described in a small percentage. However, there are few reported cases of AIHA due to cold antibodies associated with renal carcinoma. Management with corticosteroids and immunosuppressors is effective in the majority of cases, but treatment of the underlying disease is critical.

Cold agglutinin disease is a very rare haemolytic anaemia characterized by antibody-mediated haemolysis, complement activation, thrombosis and poor quality of life. In recent years, our understanding of the complement system and its role in disease has increased dramatically. However, because there is an increased risk of infection with inhibiting complement at the complement 5 and complement 3 levels, blocking the classical complement pathway is being explored instead as a way to strategically inhibit the complement system while minimizing the infection risks. Sutimlimab is a humanized immunoglobulin G4 antibody developed to inhibit the classical complement pathway. Its role and efficacy in treating patients with cold agglutinin disease will be the focus of this paper. [ABSTRACT FROM AUTHOR]

Objectives: The complement system is an important component of innate immunity. The alternative pathway (AP) amplification loop is considered an essential feed forward mechanism for complement activation. However, the role of the AP in classical pathway (CP) activation has only been studied in ELISA settings. Here, we investigated its contribution on physiologically relevant surfaces of human cells and bacterial pathogens and in antibody‐mediated complement activation, including in autoimmune haemolytic anaemia (AIHA) setting with autoantibodies against red blood cells (RBCs). Methods: We evaluated the contribution of the AP to complement responses initiated through the CP on human RBCs by serum of AIHA patients and recombinant antibodies. Moreover, we studied complement activation on Neisseria meningitidis and Escherichia coli. The effect of the AP was examined using either AP‐depleted sera or antibodies against factor B and factor D. Results: We show that the amplification loop is redundant when efficient CP activation takes place. This is independent of the presence of membrane‐bound complement regulators. The role of the AP may become significant when insufficient CP complement activation occurs, but this depends on antibody levels and (sub)class. Our data indicate that therapeutic intervention in the amplification loop will most likely not be effective to treat antibody‐mediated diseases. Conclusion: The AP can be bypassed through efficient CP activation. The AP amplification loop has a role in complement activation during conditions of modest activation via the CP, when it can allow for efficient complement‐mediated killing. [ABSTRACT FROM AUTHOR]

In his study, 29 out of 193 patients treated with ibrutinib for CLL had an AIC before treatment, including eight patients with ITP and five with Evans' syndrome. Many patients go through a prolonged course and become relapsed/refractory to a series of different interventions.3 In this study, we describe the first successful case of zanubrutinib for the treatment of ES in a 15-year-old Chinese girl with severe refractory/relapsed thrombocytopenia. Keywords: autoimmune haemolytic anaemia; Bruton's tyrosine kinase inhibitor; Evans' syndrome; immune thrombocytopenia; zanubrutinib EN autoimmune haemolytic anaemia Bruton's tyrosine kinase inhibitor Evans' syndrome immune thrombocytopenia zanubrutinib e37 e42 6 11/24/22 20221201 NES 221201 Abbreviations AIC autoimmune cytopenias AIHA autoimmune haemolytic anaemia ANC Absolute neutrophil count BCR B cell receptor BID bis in die/twice day BTK Bruton's Tyrosine Kinase BTKis Inhibitors of BTK CLL chronic lymphocyticleukaemia CMV cytomegalovirus CT computed tomography EBV Epstein-Barr virus ES Evans' syndrome Hb Haemoglobin HD-DXM high-dose dexamethasone IH hypodermic injection IVIG intravenous immunoglobulin ITP Immune thrombocytopenia MCL mantle cell lymphoma MDS myelodysplastic syndromes PDN Prednisolone PLT Platelets PNH paroxysmal nocturnal haemoglobinuria QD quaque die/every day rhTPO Recombinant human thrombopoietin SLE Systemic lupus erythematosus SYK Spleen tyrosine kinase TCM traditional Chinese medicine TMA thrombotic microangiopathies TPO-RA Thrombopoietin receptor agonist BACKGROUND Evans' syndrome (ES) was first described by Evans in 1951 and is a rare autoimmune disorder that is defined as the concomitant or sequential occurrence of Coombs positive immune thrombocytopenia (ITP) and autoimmune haemolytic anaemia (AIHA).1 The clinical manifestations of ES include anaemia, bleeding, jaundice, hepatosplenomegaly and haemoglobinuria. [Extracted from the article]

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Cold agglutinin disease, commonly affecting females in the their seventh decade of life, is otherwise a rare entity and has an incidence of one case per million people per year. Cold reactive antibody is associated with autoimmune haemolytic anaemia (AIHA) in approximately 20% of the cases. Although the occurrence of AIHA in patients with non-Hodgkin's lymphomas is well known, aggressive lymphomas such as diffuse large B cell lymphoma (DLBCL) initially presenting as cold agglutinin AIHA is extremely rare. Here, we describe a case of DLBCL presenting few months before the diagnosis as cold antibody-AIHA.xs

Autoimmune haemolytic anaemia (AIHA) is a rare immune-related adverse event and appears to be more common with anti-PD1/PDL1 than anti-CTLA4. Little is known about the safety of re-treating with anti-PD1/PDL1 or changing to anti-CTLA4. We present a case of grade 4 AIHA due to nivolumab (PD1-inhibitor) treatment in a patient with melanoma for adjuvant setting after surgery and the safeness of subsequent treatment with ipilimumab (anti-CTLA4). After the remission of AIHA with steroids, ipilimumab was started with the rationale of its different mechanism of action. Fortunately, AIHA did not recur. The mechanism by which checkpoint inhibitors cause AIHA is likely by augmenting or redirecting immune surveillance, especially by activating pre-existing red blood cell autoantibodies, but further studies must be done. To our knowledge, this is the first case published in the literature with the change of immunotherapy treatment to anti-CTLA4.

The THαβ host immunological pathway contributes to the response to infectious particles (viruses and prions). Furthermore, there is increasing evidence for associations between autoimmune diseases, and particularly type 2 hypersensitivity disorders, and the THαβ immune response. For example, patients with systemic lupus erythematosus often produce anti-double stranded DNA antibodies and anti-nuclear antibodies and show elevated levels of type 1 interferons, type 3 interferons, interleukin-10, IgG1, and IgA1 throughout the disease course. These cytokines and antibody isotypes are associated with the THαβ host immunological pathway. Similarly, the type 2 hypersensitivity disorders myasthenia gravis, Graves’ disease, graft-versus-host disease, autoimmune haemolytic anaemia, immune thrombocytopenia, dermatomyositis, and Sjögren’s syndrome have also been linked to the THαβ pathway. Considering the potential associations between these diseases and dysregulated THαβ immune responses, therapeutic strategies such as anti-interleukin-10 or anti-interferon α/β could be explored for effective management. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a multisystemic and chronic autoimmune disease with varying clinical manifestations. The role of various infectious agents in triggering the disease onset in genetically predisposed patients has been implicated in the pathogenesis of SLE. The severe acute respiratory syndrome coronavirus 2 has been reported to trigger various autoimmune diseases including SLE in few adults. Herein, we report the case of a previously well 12-year-old girl who presented with warm antibody Coombs-positive autoimmune haemolytic anaemia, 3 weeks after testing positive for COVID-19. COVID IgG antibody test was positive. During the hospital stay, she developed multisystem involvement in the form of neurological manifestations and arthritis. She was managed with steroids, intravenous (IV) immunoglobulins and supportive measures. Her anti-nuclear antibody and anti-dsDNA antibodies were positive and complement levels were low, confirming a diagnosis of SLE. Her clinical condition improved rapidly and remained neurologically normal, and serial haemoglobin showed an improving trend. IV steroids were changed to oral form, and hydroxychloroquine was also added. She remained well on 3-week follow-up.

Background: Severe autoimmune haemolytic anaemia (AIHA) in systemic lupus erythematosus (SLE) patients could be life-threatening and formidable, especially in those nonresponsive to glucocorticoids (GCs) and immunosuppressants (ISAs). Whole-blood exchange transfusion (WBE), with plasma exchange and pathogenic cell removal as well as healthy red blood cell transfusion, could be beneficial. The objective of this study was to investigate the efficacy and safety of WBE in combination with GCs/ISAs. Methods: In this retrospective study, the clinical data of 22 refractory severe SLE-AIHA inpatients between February 2016 and February 2021 were collected and analysed, among whom 14 patients had received WBE and were compared with those treated with typical second-line therapy of intravenous immunoglobulin and/or rituximab (IVIG/RTX). Results: Among the 22 severe refractory SLE-AIHA patients, eight patients received IVIG and/or RTX without WBE (group 1, IVIG/RTX, n = 8), seven patients were given WBE without IVIG/RTX (group 2, WBE alone, n = 7), and seven patients who failed initial IVIG/RTX therapy were given sequential WBE therapy (group 3 IVIG/RTX→WBE, n = 7). Fourteen patients had accepted WBE treatment regardless of prior IVIG/RTX usage (group 2 + 3, WBE ± IVIG/RTX, n = 14). On days 1, 3, 5, and 7 after corresponding therapies, patients of groups 2, 3, and 2 + 3 showed significantly higher levels of haemoglobin (Hb) than patients of group 1. Compared with patients of group 1, patients of groups 2, 3, and 2 + 3 took less time to reach and maintain Hb ≥60 g/L from baseline. Groups 2 and 2 + 3 consumed a lower dose of GCs than group 1 to reach and maintain Hb ≥60 g/L from baseline. Group 1 experienced longer hospital stays than group 2, and group 3's cost of hospitalisation is more than groups 1 and 2. Hbmin <40 g/L may be a key indicative factor for initiating WBE remedy therapy as IVIG/RTX may not be effective enough in 48–72 h in those patients with refractory severe SLE-AIHA. No severe adverse effects were observed in the WBE group. Conclusions: WBE could be a safe and beneficial alternative therapy for refractory severe SLE-AIHA. [ABSTRACT FROM AUTHOR]

BackgroundSevere autoimmune haemolytic anaemia (AIHA) in systemic lupus erythematosus (SLE) patients could be life-threatening and formidable, especially in those nonresponsive to glucocorticoids (GCs) and immunosuppressants (ISAs). Whole-blood exchange transfusion (WBE), with plasma exchange and pathogenic cell removal as well as healthy red blood cell transfusion, could be beneficial. The objective of this study was to investigate the efficacy and safety of WBE in combination with GCs/ISAs.MethodsIn this retrospective study, the clinical data of 22 refractory severe SLE-AIHA inpatients between February 2016 and February 2021 were collected and analysed, among whom 14 patients had received WBE and were compared with those treated with typical second-line therapy of intravenous immunoglobulin and/or rituximab (IVIG/RTX).ResultsAmong the 22 severe refractory SLE-AIHA patients, eight patients received IVIG and/or RTX without WBE (group 1, IVIG/RTX, n = 8), seven patients were given WBE without IVIG/RTX (group 2, WBE alone, n = 7), and seven patients who failed initial IVIG/RTX therapy were given sequential WBE therapy (group 3 IVIG/RTX→WBE, n = 7). Fourteen patients had accepted WBE treatment regardless of prior IVIG/RTX usage (group 2 + 3, WBE ± IVIG/RTX, n = 14). On days 1, 3, 5, and 7 after corresponding therapies, patients of groups 2, 3, and 2 + 3 showed significantly higher levels of haemoglobin (Hb) than patients of group 1. Compared with patients of group 1, patients of groups 2, 3, and 2 + 3 took less time to reach and maintain Hb ≥60 g/L from baseline. Groups 2 and 2 + 3 consumed a lower dose of GCs than group 1 to reach and maintain Hb ≥60 g/L from baseline. Group 1 experienced longer hospital stays than group 2, and group 3’s cost of hospitalisation is more than groups 1 and 2. Hbmin

Autoimmune Polyglandular Syndrome (APS) is a cluster of endocrine abnormalities that occur in discreet patterns in subjects with immune dysregulation and that permit treatment and anticipation of associated systemic or other hormonal deficiencies. It is classified into four subtypes based on the extent of autoimmune manifestations. APS type 3 is characterised by the presence of an autoimmune thyroid disease and another autoimmune illness, excluding Addison’s disease. Ocular manifestations of APS include keratoconjunctivitis, dry eye, corneal scarring, cataract, retinopathy and optic atrophy. Here, a case of a 23-year-old male patient with APS has been presented with a growth in the left eye for four months, with no other associated symptoms. The patient was a known case of APS type 3 with Autoimmune Haemolytic Anaemia (AIHA) since the age of five years. The patient was treated with long-term oral steroids and Azathioprine for 18 years. His visual acuity was 6/6; N6 in both eyes. A gelatinous lesion measuring 8×4 mm was located on the nasal bulbar conjunctiva of left eye, extending 3 mm onto the cornea. The lesion demonstrated intrinsic vascularity, feeder vessels and pigmentation, clinically suggestive of Ocular Surface Squamous Neoplasia (OSSN). Ultrasonography defined the extension of the lesion to involve the episclera, sclera and posterior cornea. Incisional biopsy established the diagnosis of conjunctival squamous cell carcinoma in-situ. Surgical excision was deferred in view of good visual acuity and deep scleral and corneal involvement. The patient was treated with topical Mitomycin C 0.04%, and remained on close follow-up for six months. A possible contribution of long-term intake of systemic azathioprine to the occurrence of conjunctival neoplasia can be considered.

Haemolytic anaemia can seem like a complicated topic. The constellation of reticulocytosis, increased lactate dehydrogenase levels, increased unconjugated bilirubin levels and decreased haptoglobin levels should prompt general physicians to consider haemolysis as a differential diagnosis. When further approaching haemolytic anaemia, subdividing patients into those who are 'direct antiglobulin test (DAT) positive' (immune) or 'DAT negative' (non-immune) is a simple and clinically relevant way to start to formulate a cause for the haemolytic anaemia. Immune causes of haemolytic anaemia include autoimmune haemolytic anaemia, drugs and delayed haemolytic transfusion reactions. Non-immune causes include the haemoglobinopathies (such as sickle cell disease) and microangiopathic haemolytic anaemias (such as disseminated intravascular coagulation). Early supportive care in haemolytic anaemia is important and may involve blood transfusions as well as interventions to slow the rate of haemolysis, such as steroids in autoimmune haemolytic anaemia. Complications of haemolysis include pigment gallstones, high-output cardiac failure and thromboembolism. Haemolytic anaemia should be referred to the haematologist for further investigation, however, the recognition and early management by the general physician is imperative in improving the patient's outcome. [ABSTRACT FROM AUTHOR]

Autoimmune haemolytic anaemia (AIHA) is an acquired disorder in which antibodies are produced against self-erythrocyte antigens. We distinguish those produced by cold antibodies (IgM), which may be associated with lymphoproliferative syndromes, infectious diseases, other autoimmune phenomena, as well as drugs or solid tumours. We report a case of AIHA due to cold antibodies as a paraneoplastic syndrome (PNS) in a patient with metastatic renal carcinoma. A 67-year-old man with newly diagnosed stage IV renal carcinoma with hepatic, bone, and lymph node involvement was consulted for abdominal pain. Laboratory tests showed grade 4 anaemia (4.5 g/dL), with positive direct Coombs' test C3bC3d and agglutinated red blood cells in the blood smear. AIHA by cold antibodies was labelled as PNS in the context of the patient; therefore, blood transfusion as well as treatment of the underlying disease with tyrosine kinase inhibitors (sunitinib) were initiated, with subsequent clinical and analytical improvement. AIHA due to cold antibodies is a well-known PNS in lymphoproliferative disorders, although association with solid tumours, such as Kaposi's sarcoma and non-small-cell lung cancer have also been described in a small percentage. However, there are few reported cases of AIHA due to cold antibodies associated with renal carcinoma. Management with corticosteroids and immunosuppressors is effective in the majority of cases, but treatment of the underlying disease is critical. [ABSTRACT FROM AUTHOR]

Abstract Background Rosai- Dorfman Disease (RDD) is a benign condition of unknown aetiology which is characterized by non-neoplastic proliferation of histiocytes. Pathophysiology and natural history remain obscure due to the low prevalence of disease. It is known to present with nodal or extranodal involvement and occurrence in the genitourinary system could lead to dreadful complications. RDD is diagnosed by demonstrating emperipolesis on histology and supported by S100 positivity in immunohistochemistry. Treatment is tailored individually and includes expectant monitoring, steroids, surgery, chemotherapy and radiotherapy. Prognosis will be poor if there is involvement of vital organs. We report a rare case of renal Rosai-Dorfman Disease in a 12-year-old girl which also associated with cold type autoimmune haemolytic anaemia (AIHA). Case presentation A previously healthy, 12-year-old girl presented with low grade fever and cough over one month. On examination, she was pale, mildly icteric and had a firm mass in the left hypochondrial region. Her blood count revealed significant eosinophilia, normocytic normochromic anaemia and thrombocytosis. Further laboratory investigations revealed reticulocytosis, positive urine urobilinogen, positive direct antiglobulin test and red blood cell agglutination on blood picture suggestive of autoimmune haemolytic anaemia. Ultrasound scan of abdomen revealed paraaortic and left side retroperitoneal lymphadenopathy with left renal mass. It was further evaluated by Contrast Enhanced Computed Tomography (CECT). Biopsy was done and that concluded sinus histiocytosis with massive lymphadenopathy (SHML) with positive S100 and CD1a in immunohistochemistry. Child was treated with steroids however there was no significant response as assessed by repeat CT and has been commenced on chemotherapy. Conclusion RDD is believed to be due to host immune dysregulation and precise diagnosis is imperative. It should be considered as differential diagnosis in a child presenting with massive lymphadenopathy and AIHA. Association between RDD and AIHA may possibly be explained by abnormal immune response of the host.

Objective To investigate the clinical features of AIHA/ES patients with clonal Ig/TCR gene rearrangement. Methods Ig/TCR gene rearrangements were measured by BIOMED-2 PCR. 44 primary AIHA/ES patients were enrolled in the study. Clinical characteristics were analyzed and compared between patients with and without clonal Ig/TCR gene rearrangement. Results Clonal Ig/TCR rearrangements were identified in 34.09% (15/44) patients including 18.18% (8/44) clonal Ig rearrangement and 15.91% (7/44) clonal TCR rearrangement. 11.37% (5/44) patients showed TCR γ rearrangement, and 2.27% (1/44) patient showed β rearrangement. 2.27% (1/44) patient showed both γ and β chain rearrangement. The median ages of patients with Ig/TCR clonality (8 male and 7 female) and without Ig/TCR clonality (10 male and 19 female) were 60 (16 ∼ 81) and 53 (17 ∼ 78) years old, respectively. No significant differences were found in age or gender between the two groups (p = .26, p = .378). Hb and RBC of patients with Ig/TCR clonality [(64.31 ± 5.72) g/L, (1.78 ± 0.22) × 1012/L] were significantly lower than those of patients without Ig/TCR clonality (p = .0053 and p = .0189, respectively). The percentage of reticulocytes of Ig/TCR clonality group was obviously higher than that of patients without Ig/TCR clonality (p = .0248). No significant differences were found in levels of TBIL, IBIL, LDH, FHb, Hp, IgG, IgA, IgM, IgE, C3, C4, CD5+CD19+/CD19+ ratio, and CD3+CD4+/CD3+CD8+ ratio between the two groups. Treatment response of Ig/TCR clonality group occurred significantly later than that of the non-clonality group (p = .0016). There were no differences in relapse rate, time to recurrence, and duration of remission between two groups (p = .083, p = .72, and p = .61, respectively). Conclusion AIHA/ES patients with clonal Ig/TCR gene rearrangement presented more severe haemolysis and anaemia. Longer treatment is needed for these patients to obtain remission.

Post-artesunate delayed haemolysis (PADH) is thought to occur because of delayed clearance of previously malarial infected erythrocytes spared by ‘pitting’ during treatment. We report a case of PADH following the treatment of Plasmodium (P.) falciparum malaria (32% parasitaemia), with a positive direct antiglobulin (DAT) test, suggesting an immune mechanism.

Yersinia enterocolitica infection is an uncommon but potentially fatal zoonosis, especially when it culminates with septicaemia. Post-infectious complications like reactive arthritis and erythema nodosum are well described in the literature. On the other hand, the association between yersinosis and autoimmune haemolytic anaemia (AIHA) has only been established in one clinical case. We present a case of an 87-year-old man admitted for AIHA, whose was successfully treated only after the identification and treatment of yersinosis.

Summary: Autoimmune haemolytic anaemia (AIHA) is a rare complication of allogeneic haematopoietic stem cell transplantation (HSCT), observed with an incidence of 1–5%. Paediatric age, diagnosis of non‐malignant disease, lympho‐depleting agents in the conditioning regimen, use of unrelated donor, graft versus host disease and infections have been associated with a higher risk of AIHA post HSCT. Post‐HSCT AIHA is associated with high mortality and morbidity, and it is often very difficult to treat. Steroids and rituximab are used with a response rate around 30–50%. These and other therapeutic strategies are mainly derived from data on primary AIHA, although response rates in post‐HSCT AIHA have been generally lower. Here we review the currently available data on risk factors and therapeutic options. There is a need for prospective studies in post‐HSCT AIHA to guide clinicians in managing these complex patients. [ABSTRACT FROM AUTHOR]

Autoimmune haemolytic anaemia (AIHA) is a group of disorders wherein autoantibody causes decompensated acquired haemolysis. There has been no epidemiological study of autoimmune haemolytic anaemia (AIHA) in Malaysia. This study retrospectively analysed the epidemiology of AIHA including Evan's Syndrome in a Tertiary Haematology Centre in Malaysia. Patients diagnosed with AIHA and Evan's Syndrome at 18 years old and above between 1 January 1994 to 1 October 2020 at the out-patient Haematology Clinic of Hospital Raja Permaisuri Bainun, Ipoh were selected. Patients' information was retrieved from the outpatient clinic records. A total of 71 patients were included of which predominantly female. The mean age for both genders were comparable. Ethnic stratification revealed AIHA was higher in Malays followed by Chinese and Indian. Warm AIHA was most prevalent at 40.8%, compared to cold AIHA and Evan's Syndrome (both 23.9%), and mixed AIHA (11.3%). Primary was more common than secondary AIHA followed by Evan's Syndrome. Approximately half of the secondary AIHA and secondary Evan's Syndrome were due to SLE. Overall, 67.6% of patients received corticosteroid only and 28.2% combined with immunosuppressant. Individuals at higher age and females have higher risk of developing AIHA and Evan's Syndrome. The highest prevalence was seen among the Malay ethnic. Primary warm AIHA is the most common type and majority of Evan's syndrome are secondary to autoimmune diseases. [ABSTRACT FROM AUTHOR]

Post-artesunate delayed haemolysis (PADH) is thought to occur because of delayed clearance of previously malarial infected erythrocytes spared by 'pitting' during treatment. We report a case of PADH following the treatment of Plasmodium (P.) falciparum malaria (32% parasitaemia), with a positive direct antiglobulin (DAT) test, suggesting an immune mechanism. [ABSTRACT FROM AUTHOR]

Autoimmune haemolytic anaemia (AIHA) is a rare immune-related adverse event and appears to be more common with anti-PD1/PDL1 than anti-CTLA4. Little is known about the safety of re-treating with anti-PD1/PDL1 or changing to anti-CTLA4. We present a case of grade 4 AIHA due to nivolumab (PD1-inhibitor) treatment in a patient with melanoma for adjuvant setting after surgery and the safeness of subsequent treatment with ipilimumab (anti-CTLA4). After the remission of AIHA with steroids, ipilimumab was started with the rationale of its different mechanism of action. Fortunately, AIHA did not recur. The mechanism by which checkpoint inhibitors cause AIHA is likely by augmenting or redirecting immune surveillance, especially by activating pre-existing red blood cell autoantibodies, but further studies must be done. To our knowledge, this is the first case published in the literature with the change of immunotherapy treatment to anti-CTLA4. [ABSTRACT FROM AUTHOR]

Autoimmune haemolytic anaemia (AIHA) is a complication arising from allogeneic haemopoietic stem cell transplantation (AHSCT), and it poses a significant challenge in patient management with poor outcome. We present the case of a 32-year-old Malay woman with chronic myeloid leukaemia who, after treatment failure with a tyrosine kinase inhibitor, was referred for AHSCT with HLA-matched peripheral blood stem cells donated by her younger brother. She suffered acute graft-versus-host disease and cytomegalovirus infection within three months post-transplant, followed by AIHA. She did not respond to multiple treatment modalities and had to be frequently admitted to hospital due to symptomatic anaemia which requiring frequent blood transfusion. Here, we highlight an AIHA case in post-AHSCT as a refractory disease due to resistance to standard treatment. This is a condition that requires close monitoring and care because it carries a high risk of morbidity and mortality for the patient, who unfortunately succumbed to her disease. [ABSTRACT FROM AUTHOR]

Autoimmune Polyglandular Syndrome (APS) is a cluster of endocrine abnormalities that occur in discreet patterns in subjects with immune dysregulation and that permit treatment and anticipation of associated systemic or other hormonal deficiencies. It is classified into four subtypes based on the extent of autoimmune manifestations. APS type 3 is characterised by the presence of an autoimmune thyroid disease and another autoimmune illness, excluding Addison's disease. Ocular manifestations of APS include keratoconjunctivitis, dry eye, corneal scarring, cataract, retinopathy and optic atrophy. Here, a case of a 23-year-old male patient with APS has been presented with a growth in the left eye for four months, with no other associated symptoms. The patient was a known case of APS type 3 with Autoimmune Haemolytic Anaemia (AIHA) since the age of five years. The patient was treated with long-term oral steroids and Azathioprine for 18 years. His visual acuity was 6/6; N6 in both eyes. A gelatinous lesion measuring 8x4 mm was located on the nasal bulbar conjunctiva of left eye, extending 3 mm onto the cornea. The lesion demonstrated intrinsic vascularity, feeder vessels and pigmentation, clinically suggestive of Ocular Surface Squamous Neoplasia (OSSN). Ultrasonography defined the extension of the lesion to involve the episclera, sclera and posterior cornea. Incisional biopsy established the diagnosis of conjunctival squamous cell carcinoma in-situ. Surgical excision was deferred in view of good visual acuity and deep scleral and corneal involvement. The patient was treated with topical Mitomycin C 0.04%, and remained on close follow-up for six months. A possible contribution of long-term intake of systemic azathioprine to the occurrence of conjunctival neoplasia can be considered. [ABSTRACT FROM AUTHOR]

Introduction/objective: The relationship between autoimmune haemolytic anaemia (AIHA) and antiphospholipid antibodies (aPL) has never been addressed via a meta-analysis in the paediatric age group. We evaluated the link between AIHA and aPL in childhood systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). Methods: EMBASE and PubMed were screened from inception to May 2020 and Peto's odds ratio for rare events was employed for the between group comparisons. Results: The meta-analysis included 11 articles for a total of 575 children: the pooled prevalence of AIHA was greater in (1) IgG aCL–positive than IgG aCL–negative children (39.7% vs 20.9%, p = 0.005); (2) in APS-positive than APS-negative SLE children (36.8% vs 13.2%, p = 0.01); and (3) in SLE-related APS than in primary APS children (53% vs 16.2%, p = 0.008). Conclusions: The pooled prevalence of AIHA is greatest in SLE with aPL/APS, low-moderate in SLE without aPL/APS, and lowest in primary APS. Key Points • Antiphospholipid antibodies strongly relate to autoimmune haemolytic anaemia. • Autoimmune haemolytic anaemia is more common in systemic lupus erythematosus with antiphospholipid antibodies. [ABSTRACT FROM AUTHOR]

Objective: To investigate the quantity and secretion function of cytokines-secreted CD5+ B lymphocytes in Autoimmune Haemolytic Anaemia (AIHA)/Evans syndrome (ES) patients. Methods: Twenty-five untreated AIHA/ES patients, 28 remission AIHA/ES patients and 25 healthy controls (HCs) were enrolled in this study. The quantity of CD5+B lymphocytes which produce interleukin-10 (IL-10) (CD5+IL-10+) and transforming growth factor (TGF-β1) (CD5+TGF-β1+) were detected by flow cytometry (FCM). CD5+ B lymphocytes were sorted from peripheral blood (PB) by FCM and the expression of IL-10 and TGF-β1 mRNA in CD5+ B cells were measured by real-time PCR (RT-PCR). Results: The percentage of CD5+IL-10+B cells in CD5+ B lymphocytes in newly diagnosed patients was 82.18 ± 14.78%, which being significantly higher than that of remission AIHA/ES patients (56.68 ± 24.39%) and HCs (51.90 ± 22.95%) (p .05). Conclusions: CD5+ B lymphocytes could secrete IL-10 rather than TGF- β1 which control the immune response in AIHA/ES.

Abstract Background Tuberculosis induced autoimmune haemolytic anaemia is a rare entity. The aim of this study was to explore its common presentations, investigation findings and treatment options through a systematic review of published reports. Methods PubMed, Trip, Google Scholar, Science Direct, Cochrane Library, Open-Grey, Grey literature report and the reference lists of the selected articles were searched for case reports in English on tuberculosis induced auto-immune haemolytic anaemia. PRISMA statement was used for systematic review. Quality assessment of the selected reports was done using the CARE guidelines. Results Twenty-one articles out of 135 search results were included. Thirty-three percent of patients were reported from India. More than half had fever and pallor. The mean haemoglobin was 5.77 g/dl (SD 2.2). Positive direct coombs test was seen in all patients. Pulmonary tuberculosis (43%) was most prevalent. Twenty-nine percent of patients needed a combination of anti-tuberculosis medicines, blood transfusion and steroids. Higher percentage of disseminated TB induced AIHA (67%) needed steroids in comparison to the other types of TB induced AIHA (13%). Conclusions Rarer complications of tuberculosis such as auto-immune haemolytic anaemia should be looked for especially in disease-endemic areas. Blood transfusion and steroids are additional treatment options along with the anti-tuberculosis medicines.

Additionally, causes of secondary AA other than SARS-CoV-2 infection/vaccine should not be disregarded, including other infections, drugs, and the rarer congenital bone marrow failures. Keywords: aplastic anaemia; autoimmune haemolytic anaemia; immune thrombocytopenia; coronavirus disease 2019; severe acute respiratory syndrome coronavirus-2 vaccine EN aplastic anaemia autoimmune haemolytic anaemia immune thrombocytopenia coronavirus disease 2019 severe acute respiratory syndrome coronavirus-2 vaccine 1334 1336 3 03/22/22 20220315 NES 220315 There is increasing awareness about the possible relationship between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccines and the development of haematological diseases, including autoimmune cytopenias (AICs) and complement-mediated diseases. Immune thrombocytopenia, severe acute respiratory syndrome coronavirus-2 vaccine, aplastic anaemia, autoimmune haemolytic anaemia, coronavirus disease 2019. [Extracted from the article]

Keywords: autoimmune haemolytic anaemia; health-related quality of life; patient-reported outcomes; registry EN autoimmune haemolytic anaemia health-related quality of life patient-reported outcomes registry e54 e57 4 01/20/21 20210115 NES 210115 Recent data on the incidence and prevalence figures for autoimmune haemolytic anaemia (AIHA) from the Danish national register are 1-77/100,000 person-years and 17/100,000 persons.1 Applied to the estimated mid-2019 United Kingdom (UK) population of 66,796,800,2 this would translate to around 1200 cases/year and 11,000 affected individuals. Patients identified the following research priorities: find the cause/trigger of AIHA, improve treatment, improve recognition of AIHA in primary care and establish a national database. [Extracted from the article]

To investigate the clinical features of AIHA/ES patients with clonal Ig/TCR gene rearrangement. Ig/TCR gene rearrangements were measured by BIOMED-2 PCR. 44 primary AIHA/ES patients were enrolled in the study. Clinical characteristics were analyzed and compared between patients with and without clonal Ig/TCR gene rearrangement. Clonal Ig/TCR rearrangements were identified in 34.09% (15/44) patients including 18.18% (8/44) clonal Ig rearrangement and 15.91% (7/44) clonal TCR rearrangement. 11.37% (5/44) patients showed TCR γ rearrangement, and 2.27% (1/44) patient showed β rearrangement. 2.27% (1/44) patient showed both γ and β chain rearrangement. The median ages of patients with Ig/TCR clonality (8 male and 7 female) and without Ig/TCR clonality (10 male and 19 female) were 60 (16 ∼ 81) and 53 (17 ∼ 78) years old, respectively. No significant differences were found in age or gender between the two groups (p =.26, p =.378). Hb and RBC of patients with Ig/TCR clonality [(64.31 ± 5.72) g/L, (1.78 ± 0.22) × 1012/L] were significantly lower than those of patients without Ig/TCR clonality (p =.0053 and p =.0189, respectively). The percentage of reticulocytes of Ig/TCR clonality group was obviously higher than that of patients without Ig/TCR clonality (p =.0248). No significant differences were found in levels of TBIL, IBIL, LDH, FHb, Hp, IgG, IgA, IgM, IgE, C3, C4, CD5+CD19+/CD19+ ratio, and CD3+CD4+/CD3+CD8+ ratio between the two groups. Treatment response of Ig/TCR clonality group occurred significantly later than that of the non-clonality group (p =.0016). There were no differences in relapse rate, time to recurrence, and duration of remission between two groups (p =.083, p =.72, and p =.61, respectively). AIHA/ES patients with clonal Ig/TCR gene rearrangement presented more severe haemolysis and anaemia. Longer treatment is needed for these patients to obtain remission. [ABSTRACT FROM AUTHOR]

Thymoma is an uncommon neoplasia derived from the epithelial cells of the thymus, which leads to immune dysregulation and is associated with a series of autoimmune diseases. However, the concurrence of these disease entities is rare, and the exact mechanisms of these diseases are still unclear. We have admitted several cases who were diagnosed with thymoma, autoimmune haemolytic anaemia, and pure red cell aplasia. These cases were the first to report the concurrence of these three disorders. After thymectomy, anaemia improved, haemolytic cells decreased, and haemoglobin was normalized. [ABSTRACT FROM AUTHOR]

Background: Warm autoantibodies (WAA) are antibodies that react with an antigen on a patient's own red‐blood‐cells and can complicate compatibility testing whether or not they cause clinical haemolysis. The goal of this study was to understand the overall prevalence of WAA, the risk of RBC alloimmunization and determine whether RBC selection practices have an impact on alloimmunization. Materials and methods: Records of patients (>1 year of age) with an indirect antibody detection test (IAT) and serologic evidence of WAA over a 10‐year‐period were included. Eight centres from 5 countries collectively reviewed 1 122 245 patients who had an IAT. Results: Of patients having IAT, 1214 had WAA (0·17%). Transfusion information for 1002 of the patients was available; 631 were transfused after identification of the WAA (63%); of the transfused patients, 390 received prophylactic antigen‐matched (PAM) RBCs and 241 did not. Of the 372 patients with WAA who were transfused and had serologic testing 30+ days following transfusion (30–2765 days), 56 developed new RBC alloimmunization (15·1%). Patients who were transfused using a PAM strategy were not protected from new RBC alloimmunization [14·6% (31 of 212 patients) having PAM transfusion approach compared with those not receiving PAM approach (15·6%, 25 of 160 patients, P = 0·8837)]. Conclusions: The prevalence of WAA in patients having an IAT is low (<1%). A significant portion of patients with WAA form new RBC alloimmunization (15·1%); however, the use of PAM approach for RBC selection was not found to be protective against new alloimmunization. [ABSTRACT FROM AUTHOR]

Autoimmune haemolytic anaemia (AIHA) and paroxysmal nocturnal haemoglobinuria (PNH) are two distinct causes of haemolytic anaemia. They have different mechanisms that underpin their pathogenesis and, therefore, require different treatment strategies. The direct antiglobulin test (DAT) or Coombs test is positive in cases of immune-mediated haemolytic anaemia and, thus, is positive in AIHA but negative in PNH. We report a case of a woman presenting with a haemolytic anaemia who was found to have concomitant evidence of AIHA and PNH. The case highlights the importance of carrying out a comprehensive haemolysis work-up in patients who present with haemolytic anaemia. [ABSTRACT FROM AUTHOR]

A 38-year-old female in the reproductive age group presented with anaemia in a resource-poor setting. The patient was given multiple transfusions during the course of her treatment. After a proper work-up she was diagnosed with Coomb's negative autoimmune haemolytic anaemia (AIHA). She was later treated with steroid and she showed significant improvement. Early diagnosis in her case at the primary care level with other causes of anaemia in mind could have prevented unnecessary transfusions and morbidity. Proper history and approach to anaemia is the key in a resource-poor setting.

Immune haemolytic anaemia (IHA) is characterized by an increased breakdown of red blood cells (RBCs) due to allo- or auto-antibodies directed to RBC antigens with or without complement activation. Based on the nature of the antibodies, IHA can be divided in three main categories: autoimmune, drug-induced and alloimmune-mediated IHA. There is growing evidence that the innate immune system plays an important role in the pathogenesis of IHA. Complement-mediated haemolysis with the subsequent release of cell-free haemoglobin and cellfree haem resulting in the generation of reactive oxygen species and cytotoxicity as well as the production of anaphylatoxins induce a systemic inflammatory response, which contributes to morbidity and mortality in IHA. The natural plasma scavengers of cell-free haemoglobin and cell-free haem, haptoglobin and hemopexin, respectively, are depleted in cases of chronic or severe IHA. The inducible enzyme haem oxygenase 1 (HO-1) is an efficient cellular scavenger degrading haem into anti-inflammatory products to partially limit haemmediated oxidative damage in cases of saturated scavenging capacity. Complement-targeted therapy and the therapeutic replenishment of haptoglobin and hemopexin as well as the induction of HO-1 expression might be suitable targets in the treatment of IHA. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) are changing the treatments of many patients with cancer. These immunotherapies are generally better tolerated than chemotherapy, and their adverse events are immune-related mimicking autoimmune or inflammatory conditions. Although these immune-related adverse events mainly affect the skin, endocrine glands, digestive tract, joints, liver or lungs, all the organs can be theoretically affected, and the haematopoietic system is not spared. This review of the literature will focus on the haematological immune-related adverse events (Haem-irAEs). By reviewing the largest clinical trials of ICIs, we estimate the frequency of Haem-irAEs at 3.6% for all grades and 0.7% for grades III–IV. Frequency of Haem-irAEs of all grades was found to be higher with anti–programmed cell death 1 (4.1%) or anti–programmed cell death ligand 1 (4.7%) than with anti–cytotoxic T-lymphocyte–associated protein 4 (0.5%) (p < 0.0001). From the 63 cases with Haem-irAEs reported in the literature, the mean time to the onset was found to be 10 weeks after ICI initiation, and the large range for occurrence (1–84 weeks) and the regular incidence suggest that Haem-irAEs could occur at any time after ICI therapy. Among the 63 reported cases with Haem-irAEs, the distribution was immune thrombocytopenia (n = 18, 29%), pancytopenia or immune aplastic anaemia (n = 12, 19%), neutropenia (n = 11, 17%), haemolytic anaemia (n = 10, 16%), cytokine release syndrome with haemophagocytic syndrome (n = 7, 11%) and other Haem-irAEs including bicytopenia or pure red cell aplasia (n = 5, 8%). Haem-irAEs are generally highly severe adverse reactions with a mortality rate of Haem-irAEs reported to be 14% (9 deaths among the 63 cases reported). The more severe and life-threatening Haem-irAEs were both cytokine release syndrome with haemophagocytic syndrome and pancytopenia or aplastic anaemia. Haem-irAEs induced by ICIs are potentially life-threatening. By discussing their pathophysiological aspects and clinical picture, we propose in this review clinical guidelines for management. • Haematological immune-related adverse events are mainly seen with anti-programmed cell death 1 or cell death ligand 1 immunotherapies. • They are varied including immune cytopenia's, cytokine release syndrome with haemophagocytic syndrome or eosinophil count increase. • The two most severe types were aplastic anaemia and cytokine release syndrome with haemophagocytic syndrome. • Haematological immune-related adverse events are rare events but potentially life-threatening. • If occurred, immediately hold immunotherapy even if severity is of grade I and adequately treat with steroids. [ABSTRACT FROM AUTHOR]