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Medicine Mar 2024Neuroblastoma amplified sequence (NBAS)-associated disease is an autosomal recessive disorder and a broad spectrum of clinical symptoms has been reported. However,...
RATIONALE
Neuroblastoma amplified sequence (NBAS)-associated disease is an autosomal recessive disorder and a broad spectrum of clinical symptoms has been reported. However, autoimmune mediated hemolytic anemia (AIHA) is rarely reported in NBAS disease.
PATIENT CONCERNS
A now 21-year-old male harbors heterozygous variants of c.6840G>A and c.335 + 1G>A and was found had retarded growth, hypogammaglobulinemia, B lymphopenia, optic atrophy, horizontal nystagmus, slight splenomegaly and hepatomegaly since childhood. This case had normal hemoglobin level and platelet count in his childhood. He developed AIHA first in his adulthood and then thrombocytopenia during the treatment of AIHA. The mechanism underlying a case with pronounced hypogammaglobulinemia and B lymphopenia is elusive. In addition to biallelic NBAS mutations, a germline mutation in the ANKRD26 (c.2356C>T) gene was also detected. So either autoimmune or ANKRD26 mutation-mediated thrombocytopenia is possible in this case.
INTERVENTION AND OUTCOME
He was initially managed with steroid and intermittent intravenous immunoglobulin supplement. After treatment, he responded well with a normalization of hemoglobin and serum bilirubin. But the patient subsequently experienced severe thrombocytopenia in addition to AIHA. He was then given daily avatrombopag in addition to steroid escalation. He responded again to new treatment, with the hemoglobin levels and platelet counts went back to the normal ranges. Now he was on de-escalated weekly avatrombopag and low-dose steroids maintenance.
CONCLUSION
The phenotype of this case indicates that c.335 + 1G>A NBAS variant is probably a pathogenic one and c.2356C>T ANKRD26 variant is improbably a pathogenic one. AIHA may respond well to steroid even when happened in patients with NBAS disease.
Topics: Male; Humans; Adult; Child; Young Adult; Anemia, Hemolytic, Autoimmune; Agammaglobulinemia; Thrombocytopenia; Mutation; Lymphopenia; Hemoglobins; Steroids; Neuroblastoma; China; Thiazoles; Thiophenes
PubMed: 38517998
DOI: 10.1097/MD.0000000000036975 -
Blood Advances Jun 2024Autoimmune hemolytic anemia (AIHA) is a rare autoantibody-mediated disease. For steroid and/or rituximab-refractory AIHA, there is no consensus on optimal treatment....
Autoimmune hemolytic anemia (AIHA) is a rare autoantibody-mediated disease. For steroid and/or rituximab-refractory AIHA, there is no consensus on optimal treatment. Daratumumab, a monoclonal antibody targeting CD38, could be beneficial by suppression of CD38+ plasma cells and thus autoantibody secretion. In addition, because CD38 is also expressed by activated T cells, daratumumab may also act via immunomodulatory effects. We evaluated the efficacy and safety of daratumumab monotherapy in an international retrospective study including 19 adult patients with heavily pretreated refractory AIHA. In warm AIHA (wAIHA, n = 12), overall response was 50% with a median response duration of 5.5 months (range, 2-12), including ongoing response in 2 patients after 6 and 12 months. Of 6 nonresponders, 4 had Evans syndrome. In cold AIHA (cAIHA, n = 7) overall hemoglobin (Hb) response was 57%, with ongoing response in 3 of 7 patients. One additional patient with nonanemic cAIHA was treated for severe acrocyanosis and reached a clinical acrocyanosis response as well as a Hb increase. Of 6 patients with cAIHA with acrocyanosis, 4 had improved symptoms after daratumumab treatment. In 2 patients with wAIHA treated with daratumumab, in whom we prospectively collected blood samples, we found complete CD38+ T-cell depletion after daratumumab, as well as altered T-cell subset differentiation and a severely diminished capacity for cell activation and proliferation. Reappearance of CD38+ T cells coincided with disease relapse in 1 patient. In conclusion, our data show that daratumumab therapy may be a treatment option for refractory AIHA. The observed immunomodulatory effects that may contribute to the clinical response deserve further exploration.
Topics: Humans; Anemia, Hemolytic, Autoimmune; Antibodies, Monoclonal; Female; Male; Middle Aged; Adult; Aged; Retrospective Studies; Treatment Outcome; ADP-ribosyl Cyclase 1
PubMed: 38507742
DOI: 10.1182/bloodadvances.2024012585 -
Cureus Feb 2024Warm antibody autoimmune hemolytic anemia (WAIHA) is a rare disease that leads to the destruction of red blood cells in the reticuloendothelial system through the...
Warm antibody autoimmune hemolytic anemia (WAIHA) is a rare disease that leads to the destruction of red blood cells in the reticuloendothelial system through the mediation of agglutinins (immunoglobulin G (IgG) type in most cases) that attach to the erythrocyte wall at 37 °C. The association of WAIHA and venous thromboembolism (VTE) seems to be higher than other hemolytic disorders classically associated with VTE and there is a current investigation aimed at clarifying this association and establishing some criteria to use anticoagulant treatment in patients with WAIHA. Despite this, WAIHA is a rare cause for the development of recurrent VTE under secondary prophylactic anticoagulant treatment, with only a few cases described in the literature. We present the case of a patient who developed a recurrence of deep vein thrombosis during a WAIHA episode despite treatment with acenocoumarol and a review of the literature.
PubMed: 38500896
DOI: 10.7759/cureus.54361 -
Blood Advances Mar 2024
Topics: Humans; Anemia, Hemolytic, Autoimmune; Bone Marrow; Erythropoietin
PubMed: 38470435
DOI: 10.1182/bloodadvances.2023012297 -
Archives of Iranian Medicine Dec 2023Two Iranian patients with purine nucleoside phosphorylase (PNP) deficiency are described in terms of their clinical and molecular evaluations. PNP deficiency is a rare...
Two Iranian patients with purine nucleoside phosphorylase (PNP) deficiency are described in terms of their clinical and molecular evaluations. PNP deficiency is a rare form of combined immunodeficiency with a profound cellular defect. Patients with PNP deficiency suffer from variable recurrent infections, hypouricemia, and neurological manifestations. Furthermore, patient 1 developed mild cortical atrophy, and patient 2 presented developmental delay, general muscular hypotonia, and food allergy. The two unrelated patients with developed autoimmune hemolytic anemia and T cells lymphopenia and eosinophilia were referred to Immunology, Asthma and Allergy Research Institute (IAARI) in 2019. After taking blood and DNA extraction, genetic analysis of patient 1 was performed by PCR and direct sequencing and whole exome sequencing was applied for patient 2 and the result was confirmed by direct sequencing in the patient and his parents. The genetic result showed two novel variants in exon 3 (c.246_285+9del) and exon 5 (c.569G>T) (NM_000270.4) in the patients, respectively. These variants are considered likely pathogenic based on the American College of Medical Genetics and Genomics (ACMG) guideline. PNP deficiency has a poor prognosis; therefore, early diagnosis would be vital to receive hematopoietic stem cell transplantation (HSCT) as a prominent and successful treatment.
Topics: Humans; Anemia, Hemolytic, Autoimmune; Eosinophilia; Iran; Mutation; Primary Immunodeficiency Diseases; Purine-Nucleoside Phosphorylase; Purine-Pyrimidine Metabolism, Inborn Errors
PubMed: 38431953
DOI: 10.34172/aim.2023.105 -
EJHaem Feb 2024Sarcoidosis is an inflammatory disease known to be associated with multiple autoimmune disorders. There is a restricted number of descriptions of the association between...
Sarcoidosis is an inflammatory disease known to be associated with multiple autoimmune disorders. There is a restricted number of descriptions of the association between sarcoidosis and autoimmune thrombotic thrombocytopenic purpura (aTTP). We present the case of a 63-year-old woman admitted to the hospital to investigate a possible sarcoidosis who had hemolytic anemia and thrombocytopenia, with low ADAMTS13 activity and anti-ADAMTS13 antibodies, leading to a diagnosis of aTTP. Sarcoidosis was later confirmed and the two conditions evolved separately after 6 months, questioning the link between them. Clinicians should be aware of this rare cause of thrombocytopenia in patients with sarcoidosis, as aTTP is a life-threatening condition.
PubMed: 38406537
DOI: 10.1002/jha2.848 -
Hematology, Transfusion and Cell Therapy Feb 2024Autoimmune hemolytic anemia (AIHA) is a rare, life-threatening disease in pediatrics. This article describes the clinical features, diagnostic workup, treatment and...
BACKGROUND
Autoimmune hemolytic anemia (AIHA) is a rare, life-threatening disease in pediatrics. This article describes the clinical features, diagnostic workup, treatment and outcome in patients with AIHA.
METHOD
Medical charts of under 18-year-old patients with AIHA treated at a tertiary Brazilian institution from 2006 to 2021 were retrospectively reviewed. Data analysis was primarily descriptive, using medians, interquartile ranges, and categorical variables presented as absolute frequencies.
MAIN RESULTS
Twenty-four patients (14 female, 10 male) were evaluated in this study. The median age at diagnosis was 5.99 years (range: 0.25-17.1 years) and the median hemoglobin level was 4.85 g/dL (range: 4.17-5.57 g/dL). Most had warm antibodies (83.3 %). Twelve patients (50 %) had known underlining diseases, four (16.6 %) presented with AIHA concomitant with acute infectious diseases and three (12.5 %) had an undetermined post-vaccine association. Steroids and intravenous immunoglobulin were first-line therapy in 23 cases. Seven patients (29.1 %) required second and third-line treatments (rituximab, cyclophosphamide and splenectomy). The median follow-up period was 4.4 years (range: 1.0-6.7 years). Thirteen patients (54.1 %) were discharged, five cases (20.8 %) were lost to follow-up and no patient died. The median age for the six remaining patients was 11.53 years (8.5-14.7) with all of them having complete responses with no further therapies.
CONCLUSION
Most cases of AIHA are secondary to an underlying systemic disease or have a possible correlation with infections/vaccines and respond to steroids. The second and third-line therapies for refractory and relapse cases remain a dilemma. A prospective, multicenter study is essential to address the best therapeutic combinations.
PubMed: 38402032
DOI: 10.1016/j.htct.2023.12.006 -
Diagnostics (Basel, Switzerland) Feb 2024Thrombotic microangiopathies (TMAs) comprise a distinct group of diseases with different manifestations that can occur in both pediatric and adult patients. They can be... (Review)
Review
Thrombotic microangiopathies (TMAs) comprise a distinct group of diseases with different manifestations that can occur in both pediatric and adult patients. They can be hereditary or acquired, with subtle onset or a rapidly progressive course, and they are particularly known for their morbidity and mortality. Pregnancy is a high-risk time for the development of several types of thrombotic microangiopathies. The three major syndromes are hemolysis, elevated liver function tests, and low platelets (HELLP); hemolytic uremic syndrome (HUS); and thrombotic thrombocytopenic purpura (TTP). Because of their rarity, clinical information and therapeutic results related to these conditions are often obtained from case reports, small series, registries, and reviews. The collection of individual observations, the evolution of diagnostic laboratories that have identified autoimmune and/or genetic abnormalities using von Willebrand factor post-secretion processing or genetic-functional alterations in the regulation of alternative complement pathways in some of these TMAs, and, most importantly, the introduction of advanced treatments, have enabled the preservation of affected organs and improved survival rates. Although TMAs may show different etiopathogenesis routes, they all show the presence of pathological lesions, which are characterized by endothelial damage and the formation of thrombi rich in platelets at the microvascular level, as a common denominator, and thrombotic damage to microcirculation pathways induces "mechanical" (microangiopathic) hemolytic anemia, the consumption of platelets, and ischemic organ damage. In this review, we highlight the current knowledge about the diagnosis and management of these complications during pregnancy.
PubMed: 38396391
DOI: 10.3390/diagnostics14040352 -
Indian Journal of Pathology &... Apr 2024Anemia coexisting with Gaucher disease (GD) is often associated with non-hemolytic processes. Few cases of GD with autoimmune hemolytic anemia have been reported....
Anemia coexisting with Gaucher disease (GD) is often associated with non-hemolytic processes. Few cases of GD with autoimmune hemolytic anemia have been reported. However, literature on GD with concomitant nonimmune hemolytic anemia is scarce. A 1-year 6-month-old male child presented in 2018 with complaints of palpable mass in left upper abdomen, fever, cough, and vomiting. On examination, he had pallor, hepatosplenomegaly of 2 cm and 8 cm below costal margin, respectively. A clinical diagnosis of hemolytic anemia was suspected. Complete blood count revealed Hb---6.7 g/dL, TLC---8.9 × 10 3 /μL, platelet count---180 × 10 3 /μL. Peripheral smear showed predominantly microcytic hypochromic anemia with moderate degree of anisocytosis, many nucleated red blood cells, few schistocytes, polychromatophils and corrected reticulocyte count 7.89%. S. Bilirubin was 1.1 mg/dL. Hb high-performance liquid chromatography (HPLC) of the child and his parents was within normal limit. Hematological work up revealed negative results for direct Coombs' test, osmotic fragility test, and sickling test. Test for Glucose-6-phosphate dehydrogenase deficiency was positive (39 units/trillion RBC, normal 146--376). He was transfused intermittently and given steroids to manage his anemia. He was on regular follow up during which his blood counts revealed persistent anemia and thrombocytopenia. In view of this, bone marrow was performed to exclude myelofibrosis. Aspirate smears were cellular and showed normoblastic erythroid hyperplasia. Numerous large histiocytes with basophilic fibrillary cytoplasm exhibiting "crumpled tissue paper" appearance were seen. Similar findings were seen on bone marrow trephine biopsy. Genetic testing revealed pathogenic variations in the GBA gene. Beta glucosidase enzyme levels were low while chitotriosidase was raised (1109.19 nmol/hr/mL). A final diagnosis of G6PD with GD was made. The present study shows rare association of GD with Glucose-6-phosphate dehydrogenase deficiency.
Topics: Humans; Gaucher Disease; Male; Glucosephosphate Dehydrogenase Deficiency; Infant; Bone Marrow
PubMed: 38391334
DOI: 10.4103/ijpm.ijpm_271_22 -
Clinical Case Reports Feb 2024Warm Autoimmune Hemolytic Anemia (WAHA) is the most common form of autoimmune hemolysis and there is a growing body of evidence of an association between SARS-CoV-2...
Warm autoimmune hemolytic anemia and hemophagocytic lymphohistiocytosis/macrophage activation syndrome occurring after COVID19 infection and administration of Casirivimab + Imdevimab (COVID19 monoclonal antibody).
Warm Autoimmune Hemolytic Anemia (WAHA) is the most common form of autoimmune hemolysis and there is a growing body of evidence of an association between SARS-CoV-2 infection, WAHA and a hyperinflammatory state, including hemophagocytic lymphohistiocytosis/macrophage activation syndrome. However, there is no literature to date of WAHA or hyperinflammatory state following administration of anti-SARS-CoV-2 monoclonal antibody treatment. This report documents a case of a patient with history of WAHA who developed brisk hemolysis and a hyperinflammatory state consistent with hemophagocytic lymphohistiocytosis/macrophage activation syndrome after COVID-19 infection and treatment with an anti-SARS-CoV-2 monoclonal antibody. He was successfully treated with multimodal treatment involving steroids, intravenous immunoglobulins, rituximab, anakinra, and vincristine with resolution of the hemolysis.
PubMed: 38348150
DOI: 10.1002/ccr3.8426