Bryan R. Spencer , Jodie L. White , Eshan U. Patel , Ruchika Goel , Evan M. Bloch , Aaron AR Tobian
{"title":"Eligibility Considerations for Female Whole Blood Donors: Hemoglobin Levels and Iron Status in a Nationally Representative Population","authors":"Bryan R. Spencer , Jodie L. White , Eshan U. Patel , Ruchika Goel , Evan M. Bloch , Aaron AR Tobian","doi":"10.1016/j.tmrv.2022.11.001","DOIUrl":"10.1016/j.tmrv.2022.11.001","url":null,"abstract":"<div><p>Blood collection from minority populations improves the transfusion support of patients with sickle cell disease and thalassemia, but efforts are challenged by high deferral rates for hemoglobin (Hb) eligibility thresholds. This study sought to evaluate hemoglobin and iron status of a representative US female population to assess the suitability of 12.0 g/dL as minimum hemoglobin. Data were extracted from the National Health and Nutrition Examination Surveys (NHANES), 1999-2010. A national sample designed to reflect potential female blood donors (weight ≥110 lbs, not pregnant, no infectious marker reactivity, and no blood donation in past year) aged 16 to 49 years was analyzed for Hb and serum ferritin (SF) measures by race/ethnicity (<em>N</em> = 6937). Mean Hb and SF and the prevalence of iron deficiency ([ID] SF<12 ng/mL and SF<26 ng/mL) and low Hb (<12.5 g/dL and <12.0 g/dL) were estimated. Multivariable modified Poisson regression compared the prevalence for ID or low Hb at each cutoff by race/ethnicity. Mean SF values were higher and ID prevalence was lower in Non-Hispanic (NH) White (SF = 45.3 ng/mL, SF<12 ng/mL = 8.2%) than NH Black (SF = 39.6 ng/mL, SF<12 ng/mL = 14.2%) and Hispanic (SF = 36.5 ng/mL, SF<12 ng/mL = 12.7%) females. Compared to NH White females (13.7 g/dL), mean Hb was lower in NH Black (12.6 g/dL) and Hispanic females (13.4 g/dL). The percentage with Hb<12.5 g/dL was >4 times greater in NH Black (39.1%) and >2 times greater in Hispanic females (16.5%) compared to NH White (8.6%). Within 0.5 g/dL incremental categories of Hb, NH Black had higher mean SF levels and lower prevalence of SF<12 ng/mL or <26 ng/mL compared to NH White and Hispanic females. At Hb of 12.0 to 12.4g/dL, NH Black females had better measures of iron status (SF = 39.1 ng/mL, %SF<12 ng/mL = 12.0%) than NH White (SF = 33.6 ng/mL, %SF<12 ng/mL=15.8%) and Hispanic (SF = 30.4 ng/mL, %SF<12 ng/mL=15.5%) females whose Hb was 12.5 to 12.9 g/dL. Adjusting for age and Hb, the prevalence ratio for low SF was significantly lower in NH Black compared to NH White females at both SF<26 ng/mL (adjusted prevalence ratio [aPR] = 0.83, 95%CI = 0.76-0.92) and SF<12 ng/mL (aPR = 0.66, 95%CI = 0.52-0.83). NH Black females with Hb 12.0 to 12.4g/dL have better iron stores than NH White and Hispanic females whose Hb is 12.5 to 12.9 g/dL. The distribution of Hb and iron may support the safe collection of blood for female donors below the current Hb eligibility requirement of 12.5 g/dL.</p></div>","PeriodicalId":56081,"journal":{"name":"Transfusion Medicine Reviews","volume":"37 1","pages":"Pages 27-35"},"PeriodicalIF":4.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9255301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"New Treatment Perspectives for Acute Relapses in Neuromyelitis Optica Spectrum Disorder","authors":"Itay Lotan, Michael Levy","doi":"10.1016/j.tmrv.2022.06.008","DOIUrl":"10.1016/j.tmrv.2022.06.008","url":null,"abstract":"<div><p>Neuromyelitis optica spectrum disorder (NMOSD) is a chronic autoimmune disease of the central nervous system, characterized by recurrent attacks of optic neuritis, transverse myelitis, brainstem, and/ or cerebral symptoms. Despite the current standard of care consisting of high-dose corticosteroids and therapeutic plasma exchange, many patients are left with a permanent neurological disability after each attack. With the recent advancements in understanding the pathogenic mechanisms involved in NMOSD relapses, possibilities to develop new targeted therapies are anticipated. To date, therapies targeted at inhibiting the complement cascade, inhibiting the vascular endothelial growth factor, inhibiting granulocyte migration and degranulation, and depleting B cells have been explored in phase I clinical trials, while other agents are being investigated in preclinical and early clinical trials. This review aims to discuss the potential targets for relapse treatment in NMOSD and provide the readers with a summary of the available data regarding some of the candidate agents for future application in clinical practice.</p></div>","PeriodicalId":56081,"journal":{"name":"Transfusion Medicine Reviews","volume":"36 4","pages":"Pages 230-232"},"PeriodicalIF":4.5,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10745699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Therapies in Autoimmune Peripheral Neuropathies beyond Intravenous Immunoglobulin, Plasma Exchange and Corticosteroids: An Analytical Review","authors":"Ajith Sivadasan, Vera Bril","doi":"10.1016/j.tmrv.2022.05.002","DOIUrl":"10.1016/j.tmrv.2022.05.002","url":null,"abstract":"<div><p>Autoimmune neuropathies<span><span> are often treatable. First-line immunotherapies<span> include intravenous immunoglobulin (IVIG), plasma exchange<span> and corticosteroids. However, nearly 15-30% of patients are either refractory, partially responsive or chronically dependent on these first-line agents. Lack of full response leads to increased disability in addition to adverse financial implications. Consequently, there is an unmet need for more effective treatments to manage this subset of patients. There has been a remarkable increase in the knowledge about </span></span></span>immunopathogenesis<span><span>, antigenic targets, clinical phenotype correlation, and novel therapeutic agents in the last two decades. These novel agents target specific components of the immune system (humoral, </span>cellular immunity<span>, and complement) and have the potential to improve the management of these disorders. Unfortunately, high-quality evidence from large, controlled studies is scarce considering the relative rarity of these refractory cases, heterogeneity of clinical presentations and ethical concerns limiting the use of a placebo arm. An adaptive clinical trial design in a homogenous cohort with standardized outcomes in multiple centers and the use of historical controls will likely provide valuable scientific evidence about the efficacy and safety of these therapies. In this review, we examine the status of the newer immunotherapies in the treatment of autoimmune neuropathies based on existing data.</span></span></span></p></div>","PeriodicalId":56081,"journal":{"name":"Transfusion Medicine Reviews","volume":"36 4","pages":"Pages 220-229"},"PeriodicalIF":4.5,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10457034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Current Treatment Options in Cold Agglutinin Disease: B-Cell Directed or Complement Directed Therapy?","authors":"Sigbjørn Berentsen , Geir E. Tjønnfjord","doi":"10.1016/j.tmrv.2022.05.001","DOIUrl":"10.1016/j.tmrv.2022.05.001","url":null,"abstract":"<div><p>Two major steps are identified in the pathogenesis of cold agglutinin disease; clonal B-cell lymphoproliferation and complement-mediated hemolysis. Each of these steps constitutes a target for treatment. In this focused review, we address 2 successful therapeutic approaches; the bendamustine plus rituximab combination as a highly efficacious B-cell directed therapy and the anti-C1s monoclonal antibody sutimlimab as the most extensively studied complement-targeting therapy. We describe and discuss the prospective study of bendamustine plus rituximab and 2 recent, prospective studies of sutimlimab. Bendamustine-rituximab results in a high response rate, frequent complete responses and long median response duration, and the treatment is temporary. However, this therapy is relatively slow-acting and associated with some toxicity. Sutimlimab is also highly efficacious, is far more rapidly acting, and is low-toxic. Disadvantages of sutimlimab are the lack of effect on circulatory symptoms, the probable need for indefinite treatment, and the very high costs. In cold agglutinin disease patients who require treatment, the choice should be based on an individual assessment.</p></div>","PeriodicalId":56081,"journal":{"name":"Transfusion Medicine Reviews","volume":"36 4","pages":"Pages 181-187"},"PeriodicalIF":4.5,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10745689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"BTK Inhibitors in Haematology: Beyond B Cell Malignancies","authors":"Dr Emma Leitinger , Dr Zane Kaplan","doi":"10.1016/j.tmrv.2022.06.009","DOIUrl":"10.1016/j.tmrv.2022.06.009","url":null,"abstract":"<div><p>Autoreactive B-cells are crucial in the pathogenesis of both haematologic and non-haematologic autoimmune disorders. Therapies targeting B cells and autoantibodies are widely used in clinical practice, however, many patients fail to respond to conventional treatments. An evolving understanding of molecular mechanisms underlying autoimmune haematologic disorders has facilitated the development of novel therapies, including Bruton's Tyrosine Kinase (BTK) inhibitors. BTK is fundamental in B-cell survival, and its inhibition has been used in a wide range of autoimmune and inflammatory conditions, as well as mature B cell malignancies. This paper reviews the role of BTK in immunity, evolution of BTK inhibitors, and the emerging evidence for BTK inhibitors in autoimmune haematologic conditions, primarily immune thrombocytopenia (ITP), and potential future clinical applications.</p></div>","PeriodicalId":56081,"journal":{"name":"Transfusion Medicine Reviews","volume":"36 4","pages":"Pages 239-245"},"PeriodicalIF":4.5,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10763752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"New Therapies for the Treatment of Warm Autoimmune Hemolytic Anemia","authors":"Bruno Fattizzo , Wilma Barcellini","doi":"10.1016/j.tmrv.2022.08.001","DOIUrl":"10.1016/j.tmrv.2022.08.001","url":null,"abstract":"<div><p>In this review article we provide a critical insight into recent reports evaluating innovative therapies for warm type autoimmune hemolytic anemia (wAIHA). Among published articles, we selected two reports on the use of the proteasome inhibitor bortezomib in association with dexamethasone or rituximab, one study on the spleen tyrosine kinase inhibitor fostamatinib, and a retrospective study on recombinant erythropoietin (rEPO). Among recent scientific communications, we discussed a report on the phosphoinositide 3-kinase delta inhibitor (PI3Kδi) parsaclisib. All studies highlighted a good efficacy although to be confirmed in larger trials and with limitations due to the heterogeneity of wAIHA patients enrolled, the small number of subjects, the concomitant medications allowed, and the short follow-up. Ongoing trials include new B-cell/plasma-cell targeting agents such as the Bruton tyrosine kinase inhibitors ibrutinib and rilzabrutinib, and the anti-CD38 MoAbs daratumumab and its analogue isatuximab. Further drugs in clinical trials target the complement cascade in wAIHA with complement activation, such as the C3 inhibitor pegcetacoplan and the C1q inhibitor ANX005. Finally, an interesting and non-immuno-toxic strategy is to remove the pathogenic autoantibodies via blocking the neonatal Fc receptor, by intravenous nipocalimab and subcutaneous RVT-1401. Such novel agents targeting the several immunopathological mechanisms acting in wAIHA and their possible combination, will increase the therapeutic armamentarium and possibly fill the gap of wAIHA relapsed after/refractory to rituximab. Moreover, these new target therapies may represent a tool for the unmet need of very acute cases.</p></div>","PeriodicalId":56081,"journal":{"name":"Transfusion Medicine Reviews","volume":"36 4","pages":"Pages 175-180"},"PeriodicalIF":4.5,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0887796322000396/pdfft?md5=8eb7ab87c814f8db47e830e86a264733&pid=1-s2.0-S0887796322000396-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10395284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Steroid Sparing Therapies for Antineutrophil Cytoplasmic Autoantibodies Associated Vasculitis","authors":"Maria Jose Zabala Ramirez, Duy Vu, Koyal Jain","doi":"10.1016/j.tmrv.2022.08.002","DOIUrl":"10.1016/j.tmrv.2022.08.002","url":null,"abstract":"<div><p>Antineutrophil cytoplasmic antibody (ANCA) associated vasculitis comprises a rare entity of disorders that affects primarily small and medium-sized blood vessels. Since first documented in 1897, we have come a long way trying to understand the pathogenesis and finding an optimal treatment regimen. The pathogenesis of ANCA vasculitis is not well understood and despite many advances in treatment, the morbidity and mortality remains high. Over the last decade, there have been many advancements toward elucidating the pathogenesis, optimizing current therapies, and discovering new medicines. Presently, one trend is aimed at minimizing the adverse effects of glucocorticoids by reducing their use without sacrificing efficacy and safety. A new medicine targeting the alternative complement system has emerged and intends to replace glucocorticoids. Here, we review three articles that describe these new trends in the management of ANCA vasculitis.</p></div>","PeriodicalId":56081,"journal":{"name":"Transfusion Medicine Reviews","volume":"36 4","pages":"Pages 233-238"},"PeriodicalIF":4.5,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10401713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Advances in Acquired Hemophilia A","authors":"Jacqueline N Poston , Rebecca Kruse-Jarres","doi":"10.1016/j.tmrv.2022.07.001","DOIUrl":"10.1016/j.tmrv.2022.07.001","url":null,"abstract":"<div><p>Acquired Hemophilia A (AHA) is a rare, life-threatening bleeding disorder from autoantibodies against clotting factor VIII. These autoantibodies occur with increasing incidence with advanced age and are often associated with other medical conditions such as autoimmune diseases and malignancy. Not uncommonly, AHA presents as a new bleeding disorder in a person with prior thrombosis or thrombotic risk. Treatment of AHA focuses on managing and preventing bleeding, as well as immunosuppression with the goal to eradicate the autoantibody. Despite current treatment approaches, morbidity, and mortality are high due to complications from bleeding, immunosuppression, and underlying comorbidities. The most pressing needs to improved outcome for this disease are better bleeding prophylaxis in the outpatient setting and reduction of the need for intense immunosuppression. Because of the rare nature of this disease, there is limited prospective data and most treatment standards have been based on case series. The field has recently focused on improved diagnostics and advanced risk stratification, with a potential of tailoring the need and intensity of immunosuppression. Case reports of off label use of emicizumab, a factor FVIII mimetic approved for congenital hemophilia A, suggest emicizumab may provide effective and safe bleeding prophylaxis in the outpatient setting; this could permit reducing immunosuppression and decreasing the risk of treatment related infections. Two ongoing prospective clinical trials of emicizumab will help clarify the safety and efficacy in AHA.</p></div>","PeriodicalId":56081,"journal":{"name":"Transfusion Medicine Reviews","volume":"36 4","pages":"Pages 215-219"},"PeriodicalIF":4.5,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10457052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}