Autoimmune Hemolytic Anemia Associated With Human Babesiosis.
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ABSTRACT:
SUBMITTER: Rajapakse P
PROVIDER: S-EPMC8110228 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The diagnosis of autoimmune hemolytic anemia (AIHA) can be made with a stepwise approach that aims to identify laboratory and clinical evidence of hemolysis and then determine the immune nature of hemolysis with the direct anti-globulin test. Once alternative causes for these findings have been excluded, AIHA is established, and the clinician must search for secondary causes, as well as identify the type of AIHA. Rituximab is now the preferred second-line treatment for primary warm AIHA and first-line treatment for primary cold agglutinin disease (CAD), either as monotherapy or combined with bendamustine. Complement inhibitors have shown utility in stabilizing AIHA patients with acute severe hemolysis. Future prospects are discussed and include the C1s inhibitor BIVV009 (sutimlimab) that is now entering phase 3 studies for CAD.
| S-EPMC6246027 | biostudies-literature
Project description:Autoimmune hemolytic anemia (AIHA) may be frequently challenged by infectious complications, mainly as a result of immunosuppressive treatments administered. Furthermore, infectious agents are known triggers of AIHA onset and relapse. Although being risk factors for mortality, infections are an underestimated issue in AIHA. This review will collect the available evidence on the frequency and type of infectious complications in AIHA, detailing the risk related to each treatment (i.e., steroids, rituximab, splenectomy, classic immunosuppressive agents, and new target drugs). Moreover, we will briefly discuss the infectious complications in AIHA secondary to other diseases that harbor an intrinsic infectious risk (e.g., primary immunodeficiencies, systemic autoimmune diseases, lymphoproliferative disorders, solid organ and hematopoietic stem cell transplants). Finally, viral and bacterial reactivations during immune suppressive therapies will be discussed, along with suggested screening and prophylactic strategies.
| S-EPMC7796467 | biostudies-literature
Project description:Autoimmune hemolytic anemia (AIHA) is an acquired, heterogeneous group of diseases which includes warm AIHA, cold agglutinin disease (CAD), mixed AIHA, paroxysmal cold hemoglobinuria and atypical AIHA. Currently CAD is defined as a chronic, clonal lymphoproliferative disorder, while the presence of cold agglutinins underlying other diseases is known as cold agglutinin syndrome. AIHA is mediated by autoantibodies directed against red blood cells (RBCs) causing premature erythrocyte destruction. The pathogenesis of AIHA is complex and still not fully understood. Recent studies indicate the involvement of T and B cell dysregulation, reduced CD4+ and CD25+ Tregs, increased clonal expansions of CD8 + T cells, imbalance of Th17/Tregs and Tfh/Tfr, and impaired lymphocyte apoptosis. Changes in some RBC membrane structures, under the influence of mechanical stimuli or oxidative stress, may promote autohemolysis. The clinical presentation and treatment of AIHA are influenced by many factors, including the type of AIHA, degree of hemolysis, underlying diseases, presence of concomitant comorbidities, bone marrow compensatory abilities and the presence of fibrosis and dyserthropoiesis. The main treatment for AIHA is based on the inhibition of autoantibody production by mono- or combination therapy using GKS and/or rituximab and, rarely, immunosuppressive drugs or immunomodulators. Reduction of erythrocyte destruction via splenectomy is currently the third line of treatment for warm AIHA. Supportive treatment including vitamin supplementation, recombinant erythropoietin, thrombosis prophylaxis and the prevention and treatment of infections is essential. New groups of drugs that inhibit immune responses at various levels are being developed intensively, including inhibition of antibody-mediated RBCs phagocytosis, inhibition of B cell and plasma cell frequency and activity, inhibition of IgG recycling, immunomodulation of T lymphocytes function, and complement cascade inhibition. Recent studies have brought about changes in classification and progress in understanding the pathogenesis and treatment of AIHA, although there are still many issues to be resolved, particularly concerning the impact of age-associated changes to immunity.
| S-EPMC7677104 | biostudies-literature
Project description:Bortezomib is a first-in-class, potent, selective and reversible proteasome inhibitor approved for the treatment of multiple myeloma (MM) and relapsed/refractory mantle cell lymphoma. In these diseases, bortezomib targets plasma cells and lymphocytes reducing tumor burden. Recently, preclinical evidence highlighted its efficacy in reducing long-lived plasma cells responsible of autoantibodies production in several models of autoimmune conditions. These findings paved the way to a number of experiences of bortezomib use in patients with various autoimmune conditions, including autoimmune hemolytic anemia (AIHA). The latter is a nice model of autoimmunity in hematology and is caused by the production of autoantibodies against erythrocytes resulting in various degrees of hemolytic anemia. AIHA is classified in warm and cold forms according to the thermal characteristics of the autoantibody, and first-line treatment mainly relies on steroids for warm cases and the anti-CD20 rituximab for cold ones. Relapsed/refractory cases are still an unmet need, and bortezomib has been proposed in this setting with intriguing efficacy. In this review, we collected available literature on bortezomib use in AIHA and in other immune-mediated hematologic and non-hematologic diseases. Overall, most experiences highlight bortezomib efficacy even in multi-relapsed/refractory patients and suggest to consider its use in AIHA after rituximab failure.
| S-EPMC8593301 | biostudies-literature
Project description:The lupus-prone New Zealand Black (NZB) strain uniquely develops a genetically imposed severe spontaneous autoimmune hemolytic anemia (AIHA) that is very similar to the corresponding human disease. Previous studies have mapped anti-erythrocyte Ab (AEA)-promoting NZB loci to several chromosomal locations, including chromosome 4; however, none of these have been analyzed with interval congenics. In this study, we used NZB.NZW-Lbw2 congenic (designated Lbw2 congenic) mice containing an introgressed fragment of New Zealand White (NZW) on chromosome 4 encompassing Lbw2, a locus previously linked to survival, glomerulonephritis, and splenomegaly, to investigate its role in AIHA. Lbw2 congenic mice exhibited marked reductions in AEAs and splenomegaly but not in anti-nuclear Abs. Furthermore, Lbw2 congenics had greater numbers of marginal zone B cells and reduced expansion of peritoneal cells, particularly the B-1a cell subset at early ages, but no reduction in B cell response to LPS. Analysis of a panel of subinterval congenic mice showed that the full effect of Lbw2 on AEA production was dependent on three subloci, with splenomegaly mapping to two of the subloci and expansions of peritoneal cell populations, including B-1a cells to one. These results directly demonstrated the presence of AEA-specific promoting genes on NZB chromosome 4, documented a marked influence of background genes on autoimmune phenotypes related to Lbw2, and further refined the locations of the underlying genetic variants. Delineation of the Lbw2 genes should yield new insights into both the pathogenesis of AIHA and the nature of epistatic interactions of lupus-modifying genetic variants.
| S-EPMC3311724 | biostudies-literature
Project description:Autoimmune cytopenias (AICs) have been reported as a common complication in chronic lymphocytic leukemia (CLL) with autoimmune hemolytic anemia (AIHA), accounting for most cases. According to iwCLL guidelines, AICs poorly responsive to corticosteroids are considered indication for CLL-directed treatment. Chemo-immunotherapy has classically been employed, with variable results, and little data are available on novel agents, the current backbone of CLL therapy. The use of idelalisib in the setting of AICs is controversial and recent recommendations suggest avoiding idelalisib in this setting. Ibrutinib, through ITK-driven Th1 polarization of cell-mediated immune response, is known to produce an immunological rebalancing in CLL, which stands as a fascinating rationale for its use to treat autoimmunity. Although treatment-emergent AIHA has rarely been reported, ibrutinib has shown rapid and durable responses when used to treat AIHA arising in CLL. There is poor evidence regarding the role of BCL-2 inhibitors in CLL-associated AICs and the use of venetoclax in such cases is debated. Furthermore, their frequent use in combination with anti-CD20 agents might represent a confounding factor in evaluating their efficacy. In conclusions, because of their ability to mitigate an immunological dysregulation that is (at least partly) responsible for autoimmunity in CLL, to date BTK-inhibitors stand out as the most suitable choice when treatment of autoimmune cytopenias is required.
| S-EPMC8151128 | biostudies-literature
Project description:MethodsWe report the case of a 73-year-old Saudi female who presented with severe thrombocytopenia and mild autoimmune hemolytic anemia associated with brucellosis. The coexistence of published cases of two hematological disorders with brucellosis is rare.ResultsDespite the initial treatment with eltrombopag and intravenous immunoglobulin (IVIG), our patient's platelets count remained low and significantly improved after initiation of brucellosis treatment in the form of rifampicin and doxycycline. Discussion. We conclude by reviewing the case that in many parts of Saudi Arabia, brucellosis remains a prevalent infection. Hence, it should be considered as a possible diagnosis in febrile individuals with no localizing indications and the presence of severe thrombocytopenia in acute febrile illness. Although it is a rare association, it could be related to brucellosis.ConclusionThis is our region's first published case of severe thrombocytopenia and mild autoimmune hemolytic anemia associated with brucellosis. It contributes to the literature on the successful use of rifampicin and doxycycline to treat hematological disorders associated with brucellosis.
| S-EPMC9883092 | biostudies-literature
Project description:Thrombotic manifestations are a hallmark of many auto-immune diseases (AID), specially of warm autoimmune hemolytic anemia (wAIHA), as 15 to 33% of adults with wAIHA experience venous thromboembolic events (VTE). However, beyond the presence of positive antiphospholipid antibodies and splenectomy, risk factors for developing a VTE during wAIHA have not been clearly identified. The aim of this retrospective study was to characterize VTEs during wAIHA and to identify risk factors for VTE. Forty-eight patients with wAIHA were included, among whom 26 (54%) had secondary wAIHA. Eleven (23%) patients presented at least one VTE, that occurred during an active phase of the disease for 10/11 patients (90%). The frequency of VTE was not different between primary and secondary AIHA (23.7 vs. 19.2%; p = 0.5). The Padua prediction score based on traditional risk factors was not different between patients with and without VTE. On multivariate analysis, total bilirubin ? 40 ?mol/L [odds ratio (OR) = 7.4; p = 0.02] and leucocyte count above 7x10(9)/L (OR = 15.7; p = 0.02) were significantly associated with a higher risk of thrombosis. Antiphospholipid antibodies were screened in 9 out the 11 patients who presented a VTE and were negative. Thus, the frequency of VTE is high (23%) during wAIHA and VTE preferentially occur within the first weeks of diagnosis. As no clinically relevant predictive factors of VTE could be identified, the systematic use of a prophylactic anticoagulation should be recommended in case of active hemolysis and its maintenance after hospital discharge should be considered. The benefit of a systematic screening for VTE and its procedure remain to be determined.
| S-EPMC6224177 | biostudies-literature
Project description: Not available
| S-EPMC8661945 | biostudies-literature
Project description:IntroductionA small number of retrospective studies suggest AIHA to be associated with an increased risk to suffer from thromboembolic events. However, based on these studies it remains unclear whether the complement activation per is a risk factor to develop thromboembolic events in AIHA patients. The aim of this retrospective study is to investigate the incidence of thromboembolic events and the relation to complement activation in a cohort of AIHA patients.Patients and methodsWe included 77 patients in this study with a positive DAT and hemolytic parameters or with AIHA diagnosis based on the medical report. The included patients were screened for thromboembolic events (TEE) and have been stratified in groups with and without complement activation based on the positivity for complement in the DAT.ResultsOf the 77 included patients, 51 (66%) had warm AIHA, 13 (17%) cold-AIHA, 5 (7%) mixed AIHA, and 8 (10%) atypical AIHA, respectively. Primary and secondary AIHA was diagnosed in 44% and 56%, respectively. Twenty patients (26%) suffered from TEE. The majority (80%) of these patients suffered from warm AIHA and 10% from cold-AIHA. Hemolysis parameters did not differ in patients with and without TEE. There was no correlation with complement activation as evidenced by a positivity for complement in the monospecific DAT with the occurrence of TEE.ConclusionAIHA is associated with an increased risk of TEE. Based on these results prophylactic anticoagulation might be considered as soon as the diagnosis of AIHA is confirmed.
| S-EPMC9297871 | biostudies-literature