Occurrence Of Autoimmune Hemolytic Anemia Research Articles

Evan’s syndrome, primary or secondary? Navigating the diagnostic puzzle

Evans syndrome (ES) is a rare autoimmune disorder characterized by the simultaneous or sequential occurrence of autoimmune hemolytic anemia (AIHA) and immune thrombocytopenic purpura (ITP). Distinguishing between primary and secondary forms is crucial for management. This report presents a 69-year-old male with bleeding gums, anemia, and thrombocytopenia, who was diagnosed with ES following an extensive workup. Multiple potential triggers, including recent vaccinations, antibiotic use, past tuberculosis, and skin malignancies, were identified, highlighting the multifactorial nature of ES. The patient was treated with glucocorticoids, intravenous immunoglobulin (IVIG), Rituximab, and Romiplostim resulting in improved hematologic parameters. This case underscores the diagnostic challenges and importance of individualized therapeutic approaches in managing ES. Understanding the potential triggers and underlying immune dysregulation is pivotal for accurate diagnosis and effective treatment.

Evans Syndrome in a Patient with Auto Immune Thyroiditis – A Rare Association

A 46-year-old woman, diagnosed with hypothyroidism, was on treatment with synthetic thyroxine 100 micrograms per day for one year. She complained of recent-onset exertional dyspnoea, and had malaise, lethargy, and pica. Investigations revealed significant anaemia and severe thrombocytopenia, necessitating blood transfusion. She had Coombs-positive autoimmune haemolytic anaemia and immune thrombocytopenic purpura, confirming a diagnosis of Evans syndrome. She also had a positive antinuclear antibody test but had no other notable findings of autoimmune disease, suggesting a diagnosis of primary Evans syndrome. The patient was treated with intravenous dexamethasone for four days, followed by oral prednisolone at 1mg/kg/ day, with supplemental calcium and vitamin D. Thyroperoxidase antibody was positive and there was reduced uptake in thyroid scintigraphy, confirming a diagnosis of autoimmune thyroiditis. Hashimoto’s thyroiditis frequently coexists with non-endocrine autoimmune disorders. Presence of antithyroid antibodies is sometimes observed in Evans syndrome, a condition where there is simultaneous occurrence of autoimmune Haemolytic Anaemia, Cytopoenia and immune thrombocytopenic purpura. However, the development of Evans syndrome in patients with overt hypothyroidism and Hashimoto’s thyroiditis is rare. This case implies the potential existence of a shared immunogenetic pathway among three distinct autoimmune diseases, namely autoimmune haemolytic anemia, immune thrombocytopenic purpura, and Hashimoto’s thyroiditis, in the pathogenesis.

Autoimmune hemolytic anemia during pregnancy and puerperium: an international multicenter experience

AbstractRelapsing or occurring de novo autoimmune hemolytic anemia (AIHA) during pregnancy or puerperium is a poorly described condition. Here, we report 45 pregnancies in 33 women evaluated at 12 centers from 1997 to 2022. Among the 20 women diagnosed with AIHA before pregnancy, 10 had a relapse. An additional 13 patients developed de novo AIHA during gestation/puerperium (2 patients had AIHA relapse during a second pregnancy). Among 24 hemolytic events, anemia was uniformly severe (median Hb, 6.4 g/dL; range, 3.1-8.7) and required treatment in all cases (96% steroids ± intravenous immunoglobulin, IVIG, 58% transfusions). Response was achieved in all patients and was complete in 65% of the cases. Antithrombotic prophylaxis was administered to 8 patients (33%). After delivery, rituximab was administered to 4 patients, and cyclosporine was added to 1 patient. The rate of maternal complications, including premature rupture of membranes, placental detachment, and preeclampsia, was 15%. Early miscarriages occurred in 13% of the pregnancies. Fetal adverse events (22% of cases) included respiratory distress, fetal growth restriction, preterm birth, AIHA of the newborn, and 2 perinatal deaths. In conclusion, the occurrence of AIHA does not preclude the ability to carry out a healthy pregnancy, provided close monitoring, prompt therapy, and awareness of potential maternal and fetal complications.

Cold agglutinin autoimmune haemolytic anaemia as an initial presentation of diffuse large B cell lymphoma

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.

Aautoimmune Hemolytic Anemia: Pattern of Clinical Presentation and Management Outcome — a Nine Year Observation from a Tertiary Care Hospital in Saudi Arabia

Introduction: Autoimmune hemolytic anemia (AIHA) is characterized by production of auto-antibodies that bind to antigen on the erythrocyte surface that leads to its premature destruction and removal from the circulation by macrophages. Occurrence of AIHA in children and adolescents is rare, exact incidence unknown. Objective of this retrospective study was to assess clinical and laboratory characteristics, and management outcome of patients diagnosed with AIHA seen at Pediatric Hematology/Oncology department of King Faisal specialist Hospital and Research Center ,Riyadh from 2005 to 2014. Method: Retrospective chart review of patients (1-14 yrs.) diagnosed with AIHA was conducted. Children were excluded if they have congenital hemolytic anemia, such as hemoglobinopathies, congenital membranopathy and erythrocyte enzyme deficiencies. Result: Thirty-one patients identified, 19(61%) female and 12(39%) male with a median age at diagnosis of 6 years (0.1-12.4). The direct Coombs test was positive in 23 (74%) patients. Underlying diseases observed as cause of AIHA in 14 (45%) patients: majority secondary to viral infections followed by severe combined immunodeficiency syndrome post bone marrow transplant GVHD complication, while systemic lupus erythematosus, antiphospholipid antibody syndrome, autoimmune hepatitis, hypereosinophilic syndrome, Hyper IgE syndrome, post-liver transplant, diabetes was observed in individual cases. Remaining 17 (55%) patients diagnosed as primary AIHA .Corticosteroids and/or immunoglobulin was given as first line of treatment to 64.5% (20) patients while 35.5% (11) required Rituximab and/or splenectomy as second line of treatment, of which 73%(8) were diagnosed as primary AIHA. Five-year overall survival (Kaplan-Meir) rate of 89% was observed with twenty-seven alive patients showing partial or complete response ,while four patients died due to underlying diseases.Conclusion: Our results demonstrates patients responding to first line of treatment, however serious cases required management through second line of treatment. Further, a regional multicenter observational study will enable better understanding of differences in disease presentation and treatment outcomes. DisclosuresNo relevant conflicts of interest to declare.

Autoimmune hemolytic anemia in COVID-19 patients, the « transmissible » direct Coombs test

Background: Like other viruses, the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) appears to be responsible for several autoimmune complications. The occurrence of autoimmune hemolytic anemia has been described in several case reports. This AIHA was also noticeable by the important number of blood transfusions required for COVID-19 (coronavirus disease 2019) patients. By investigating RBC coating autoantibodies, this article attempts to clarify the autoimmune aspect of the anemia in the context of SARS-CoV-2 infection. Results: A large population of COVID-19 patients selected at Saint-Luc University Hospital showed an average of 44% DAT positivity. In this population, the intensive care patients were more prone to DAT positivity than the general ward patients (statistically significant result). The positive DAT appeared « transmissible » to other RBCs via COVID-19 DAT-positive patient’s plasma. Conclusion: The strongest hypothesis explaining this observation is the targeting of cryptic antigens by autoantibodies in COVID-19 patients.

Zespół Evansa – praca poglądowa

Evans syndrome (ES) is an autoimmune disease characterized by concurrent or sequential occurrence of autoimmune hemolytic anemia, immune thrombocytopenia and less frequently autoimmune neutropenia. ES is a rare situation that represents up to 7% of autoimmune haemolytic anaemia (AIHA) and around 2% of immune thrombocytopenia (ITP). The syndrome is characterized by a chronic, relapsing, and potentially fatal course requiring long-term immunosuppressive therapy. Treatment is based on corticosteroids and immunoglobulin injections depending on how the disease begins. Second-line treatment for refractory ES includes rituximab, mofetil mycophenolate, cyclosporine, vincristine, azathioprine, sirolimus and thrombopoietin receptor agonists. This syndrome often occurs with other autoimmune diseases, such as systemic lupus erythematosus (SLE), common variable immunodeficiency (CVID), and autoimmune lymphoproliferative syndrome (ALPS).

Laboratory-confirmed bloodstream infection in systemic lupus erythematosus: Risk profiling and short-term mortality.

To delineate laboratory-confirmed bloodstream infection (LCBI), analyze risk factors for its occurrence and predictors for its short-term mortality in systemic lupus erythematosus (SLE) patients.Methods A single center, retrospective, case-controlled study was performed in 159 SLE patients (2013-2019) to identify risk factors of LCBI by comparing patients with LCBI (n = 39) to those without infection (n = 120). The predictors associated with 30-day mortality in LCBI patients were also analyzed. Altogether 40 bacteria strains were isolated in 39 LCBI patients with a predominance of the gram-negative bacilli (24 strains, 60.0%). Escherichia coli and Staphylococcus aureus were the leading Gram-negative and Gram-positive microorganisms, respectively. Occurrence of LCBI was independently predicted by: SLE disease duration >4 years, SLEDAI score >4 points, glucocorticoids dose >7.5 mg/d and the previous or concomitant occurrence of autoimmune hemolytic anemia (AIHA) or thrombotic microangiopathy (TMA). Based on the identified risk factors, we developed a matrix model for the risk of future LCBI. The 30-day mortality (39 cases) was 23.1% and healthcare-associated LCBI was a predictor for 30-day mortality in SLE patients compared with community-acquired LCBI. Longer duration, higher disease activity and glucocorticoids dose, and occurrence of AIHA or TMA were risk factors of LCBI in SLE and its poor short-term prognosis may attribute to healthcare-associated LCBI.

Autoimmune cytopenia in chronic lymphocytic leukemia: diagnosis and treatment.

Treatment response and survival of 83patients with CLL complicated by immune cytopenia (IC) were analyzed. Treatment schedules in 58medicated patients included corticosteroids; chemotherapy (COP, CHOP regimens), immunotherapy (rituximab alone), immunochemotherapy (rituximab-containing regimens- R-COP, R-CHOP). Twenty-five patients underwent splenectomy. The use of corticosteroids, as the first line of treatment, resulted in short-term remission in most patients. Chemotherapy was effective in a half of CLL patients, but duration of the remission did not exceed 32months in CLL associated with autoimmune hemolytic anemia and immune thrombocytopenia. After rituximab monotherapy (10patients) the stable remission was reached in 60% of the patients with median relapse-free survival of 40months. Rituximab containing chemotherapy (22patients) caused the long-term remission in 72% of the patients with median relapse-free survival of 76months. Splenectomy performed in 25patients with CLL complicated by IC was effective in 70% of the patients. The outcome of splenectomy depends on IC entity. The best response was registered in associated immune thrombocytopenia (median overall survival 118months), the worst- in Fisher- Evans syndrome (15months). The treatment of patients with CLL complicated by ICs should be individualized. For CLL patients without significant enlargement of lymph nodes and spleen, low lymphocytosis, associated with autoimmune hemolytic anemia or immune thrombocytopenia, the monotherapy with rituximab is optimal. In case of occurrence of autoimmune hemolytic anemia, immune thrombocytopenia or Fisher- Evans syndrome in CLL patients with enlargement of lymph nodes, spleen, significant lymphocytosis, the use of R-COP or R-CHOP schemes, 4-6courses, is the most effective. Splenectomy is indicated in patients with massive splenomegaly, the resistance to medication, recurrent relapses after adequate therapy.

P2.27: Bortezomib for refractory autoimmune hemolytic anemia after intestinal transplantation

Introduction: Autoimmune Hemolytic anemia (AIHA) after solid organ transplantation is a relatively rare but severe complication. In contrast, after intestinal transplantation the incidence is up to 12.2% and generally occurs between 8–10 months after transplantation. Published therapeutic regimes include high-dose corticosteroids, intravenous immunoglobulin, plasmapheresis, rituximab and a switch of tacrolimus-immunosuppression towards other options, but the anemia can be refractory to this treatment. The overall mortality rate of AIHA is about 8%. Bortezomib is a selective and reversible proteasome 26S inhibitor that directly inhibits antibody production through plasma cell depletion, it is registered as a treatment of multiple myeloma and chronic cold agglutin disease after allogenic hematopoietic stamcell transplantation (HSCT). Methods: In this case-report we describe a 5-year old boy with microvillous inclusion disease who developed severe haemolytic anemia (Coombs negative) circa one year after multivisceral transplantation, which was unresponsive to conventional therapy with high dose steroids, IVIG and a switch from tacrolimus to cyclosporine. Plasmapheresis was not feasible due to circulatory instability. Because we ran out of therapeutic options a trial with bortezomib (Velcade®) at a dose of 1.0–1.3 mg/m2was given every 3 days, four times in total (with a second course 10 days later). Results: We observed a rapid and sustained raise in haemoglobin within the first week after administration of bortezomib. During the treatment he developed a transient increased in stoma production, leucopenia and a raise in transaminase. Three years later he is doing well and never relapsed. Conclusion: This is the first report to describe the use of bortezomib in the treatment of refractory autoimmune hemolytic anemia after multivesceral transplantation. In our case the therapy was relatively well tolerated and gave a fast and sustained favourable response with a long-term follow-up of over 3 years. The occurrence of AIHA and its treatment after multivisceral transplantation should be the subject of future registry studies to collect additional experience and explore the optimal therapeutic approach. Bortezomib should be regarded as an important therapeutic alternative for AIHA after solid organ transplantation.

Novel Alternative Treatment to Plasmapheresis in Evans Syndrome

Evans syndrome is a rare haematological disease characterised by concurrent occurrence of autoimmune haemolytic anaemia (AIHA) and idiopathic thrombocytopenic purpura. The autoimmune haemolysis can lead to hyperbilirubinaemia, profound anaemia and haemodynamic instability. It can be difficult to treat and when refractory to medical treatment it could necessitate emergency splenectomy. Plasmapheresis is used in refractory haemolytic anaemia to aid removal of disease causing autoimmune complexes whilst immunomodulators act to reduce autoantibody response and effectiveness. However, this is an expensive and resource intensive process that is limited to tertiary referral centres. In this case study we present a successful novel alternative for life threatening AIHA in Evans Syndrome using haemofiltration with on-going fresh frozen plasma transfusion when resources are limited or it is not an accessible method.

A rare combination of autoimmune hemolytic anemia and primary antiphospholipid syndrome evolving into systemic lupus erythematosus

The association of autoimmune hemolytic anemia (AIHA) with primary antiphospholipid antibody syndrome (primary APS) has not been well established. However, the occurrence of AIHA in primary APS may define a subgroup of patients with a significant risk for subsequent development of SLE. We report a case of 28 year old male who presented with clinical features of cerebral arterial thrombosis and symptomatic anemia. Subsequently the diagnosis of primary APS and warm type AIHA was made. Patient was treated for cerebral thrombosis along with glucocorticoids and least incompatible red cell concentrates. After a regular follow up of 20 months, the patient developed positivity for antinuclear antibody and oral mucosal ulcers confirming the diagnosis of SLE. This case emphasizes that patients with primary APS should always be evaluated for AIHA as this combination is not impossible, though rare. It poses a significant risk of development of SLE. Transfusion medicine specialist has a role to play in the diagnosis and management of AIHA.

G490(P) Coombs positive autoimmune haemolytic anaemia complicating post streptococcal glomerulonephritis. (a very rare occurrence)

Introduction Post streptococcal glomerulonephritis (PSGN) is the most common type of glomerulonephritis in children. Anaemia is one of its complications and is commonly secondary to fluid retention. We describe a very rare occurrence of Autoimmune Haemolytic Anaemia (AIHA) in a 10 year old girl who presented with post streptococcal glomerulonephritis. This case serves to alert the clinician about this rarely reported association. Case report A 10 year girl was admitted with a 12 day history of diarrhoea and vomiting. She had been treated for pustular tonsillitis 6 weeks prior. Cola coloured urine was noted at presentation. She has no significant past medical history. She was oliguric, pale, oedematous, hypertensive with haematuria. Initial investigations showed a mixed nephritic/nephrotic picture with direct coomb’s test (DAT) positive haemolytic anaemia with spherocytes on the blood film. Her DAT was negative for anti-gG, but positive anti-C3b-C3d, indicating that the auto–antibodies were IgM in nature 4. She was transfused in view of symptomatic anaemia (Hb: 60 grams/L) and commenced on antihypertensive medication prior to her transfer to a tertiary renal unit. Her renal biopsy showed a crescentic glomerulonephritis with the characteristic features of acute phase, PSGN along with acute tubular injury. She had an increased ASO titre and antiDNAase level. Her initial C3 was low, with normal C4 confirming PSGN. Her renal function improved on dialysis. Though the acute kidney injury has improved, she continues to have proteniuria, and is on antihypertensive medication. However, her haemolytic anaemia has resolved completely. Discussion The combination of AIHA and PSGN is very rare, to our knowledge this might be the first reported case in UK A cross reaction between antibodies induced by streptococcal infection against the red blood cells has been described as a possible mechanism. Both streptolysin O antigen and NAD–glycohydrolase (NADase) may play a role in causing haemolysis. Intravascular haemolysis resulting in haemoglobinuria could aggravate the acute kidney injury, hence the importance of recognising this association. Our patient’s haemolytic anaemia improved along with her renal recovery. Conclusion In children presenting with severe anaemia in the context of PSGN, the possibility of AIHA must be considered.

Concomitant Cases of Primary Biliary Cirrhosis and Autoimmune Hemolytic Anemia: Literature Review

Although autoimmune diseases are often concomitant, the coexistence of primary biliary cirrhosis (PBC) and autoimmune hemolytic anemia (AIHA) is not common. This is a review of the English and Japanese literature, regarding concomitant cases of PBC and AIHA. Among the 23 concomitant cases, PBC was diagnosed first in 10 cases and both diseases were almost simultaneously diagnosed in the remaining 13 cases. This suggests that there have been few concomitant cases in which AIHA developed first before the development of PBC. Moreover, there may be no correlation between the occurrence of AIHA and the staging or progression of PBC.

Drug-induced anaemia: a decade review of reporting to the Italian Pharmacovigilance data-base.

Studies investigating drug-induced anaemia are relatively scarce and mostly related to specific drugs or patients with specific pathologies. To analyse all reports of suspected drug-induced anaemias recorded in the National Pharmacovigilance Database of the Italian Medicines Agency. The cases of suspected drug-induced anaemias analysed were those retrieved from the Italian National Pharmacovigilance Database from January 2001 to December 2013. The active substances involved were 375 in 3,305 reports of drug-induced anaemia; of these, 72 % were reported as serious. In 35 % of the reports patients were in polytherapy. In 24.3 % of the cases relevant DDIs were identified. We found a PRR value of 57.29 for peginterferon alfa-2a, of 12.57 for ribavirin, of 13 for flu vaccine for the occurrence of autoimmune haemolytic anaemia. The drugs mostly involved in the cases where the Naranjo causality was probable or possible were acetylsalicylic acid, warfarin, ribavirin, peginterferon alfa-2a, carboplatin and acenocoumarol. A possible signal was detected for peginterferon alfa-2a, ribavirin and flu vaccine in the occurrence of autoimmune haemolytic anaemia. A great involvement of clopidogrel, enoxaparin, warfarin, ticlopidine and acetylsalicylic acid in preventable DDI-induced anaemia was detected, highlighting a poor awareness among healthcare providers on this issue.

Tuberculosis and autoimmune hemolytic anemia: Case report and literature review

Tuberculosis (TB) is a mycobacterial infectious disease that can affect any organ system. The wide varieties of manifestations that TB can present with make the disease a challenge for treating physicians. Anemia is commonly seen in patients with TB, and it is usually anemia of chronic disease. However, the occurrence of autoimmune hemolytic anemia in the setting of TB infection is rare.

B‐cell receptor configuration and adverse cytogenetics are associated with autoimmune hemolytic anemia in chronic lymphocytic leukemia

The development of autoimmune hemolytic anemia (AIHA) in patients with chronic lymphocytic leukemia (CLL) is associated with specific biological features. The occurrence of AIHA was hereby investigated in a retrospective series of 585 CLL patients with available immunoglobulin heavy chain variable (IGHV) gene status. AIHA occurred in 73 patients and was significantly associated with an IGHV unmutated (UM) status (P < 0.0001) and unfavorable [del(17)(p13) and del(11)(q23)] cytogenetic lesions (P < 0.0001). Stereotyped HCDR3 sequences were identified in 29.6% of cases and were similarly represented among patients developing or not AIHA; notably, subset #3 was associated with a significantly higher risk of AIHA than the other patients (P = 0.004). Multivariate analysis showed that UM IGHV, del(17)(p13) and del(11)(q23), but not stereotyped subset #3, were the strongest independent variables associated with AIHA. Based on these findings, we generated a biological risk score for AIHA development according to the presence of none (low risk), one (intermediated risk), or two (high risk) of the independent risk factors. Overall, our data indicate that UM IGHV status and/or unfavorable cytogenetic lesions are associated with the risk of developing secondary AIHA in CLL patients and suggest a possible role of specific stereotyped B-cell receptor subsets in a proportion of cases.

Autoimmune Hemolytic Anemia Following MF59-Adjuvanted Influenza Vaccine Administration: A Report of Two Cases

To describe 2 cases of autoimmune hemolytic anemia (AIHA) following the administration of MF59-adjuvanted influenza vaccine. An 83-year-old white woman developed persistent hyperpyrexia, polyarthralgia, and lower limb hypostenia about 2 days after receiving influenza vaccine. Clinical signs and laboratory evaluations suggested AIHA. The patient was treated with high-dose corticosteroids and immunoglobulins, and her clinical condition improved. A 74-year-old white woman developed severe abdominal pain and asthenia 3 days after the administration of influenza vaccine. Clinical signs and laboratory evaluations disclosed AIHA. She was treated with corticosteroids, rehydration, and blood transfusion; however, she died about 48 hours after hospitalization. AIHA has been rarely described following influenza vaccine administration. In the cases described here, the causal relationship between influenza vaccination and the occurrence of AIHA, assessed by means of World Health Organization criteria, was scored as probable. It has been proposed that the mechanism whereby vaccines induce autoimmune responses can be molecular mimicry, although a possible role of other vaccine constituents, with particular regard for adjuvants, such as MF59, can not be excluded. Squalene, a constituent of MF59, has been suggested as a causative agent of autoimmune reactions. However, it is not clear how and under what conditions squalene can cause immune responses. Influenza vaccination may rarely trigger severe AIHA, shortly after vaccine administration. A mechanism of molecular mimicry is probably involved in the development of these reactions, although the possible role of adjuvants can not be excluded. Patients should be instructed to report signs and symptoms of autoimmune disorders occurring in the first weeks after administration of influenza vaccine.

Autoimmune hemolytic anemia in patients with chronic lymphocytic leukemia is associated with IgVH status

Autoimmune hemolytic anemia in patients with chronic lymphocytic leukemia is associated with IgVH status

Neonatal familial Evans syndrome associated with joint hypermobility and mitral valve regurgitation in three siblings in a Saudi Arab family.

The occurrence of autoimmune hemolytic anemia and immune thrombocytopenia in the absence of a known underlying cause led to the diagnosis of Evans syndrome in a 9-month-old male. Subsequently, a similar diagnosis was made in two siblings (a 3-year-old boy and a 1-day-old girl). The 9-month-old had a chronic course with exacerbations. He was treated with steroids, intravenous immunoglobulin and colchiccine with a variable response. He died of congestive heart failure at the age of 8 years. The brother's disease course was one of remission and exacerbation. With time, remissions were prolonged and paralleled an improvement in joint hypermobility. The sister died of sepsis after a chronic course with severe exacerbattions. Only two families with Evans syndrome have been reported in the English medical literature. In one report (in a Saudi Arab family), the disease was associated with hereditary spastic paraplegia.