Since anemia is associated with poor health outcomes, the prevalence of anemia is a significant public health indicator. Even though anemia is primarily caused by iron deficiency, low oxygen-carrying ...capacity may result from other conditions such as chronic diseases, which remain a relevant health concern in the United States. However, studies examining current rates of anemia in the total US population and in more specific subgroups are limited. Data from five National Health and Nutrition Examination Surveys (NHANES) from 2003 to 2012 were analyzed to assess two outcomes: anemia and moderate-severe anemia, which were based upon serum hemoglobin levels (Hb) as per World Health Organization (WHO) definitions. Statistical analysis using SAS examined temporal trends and the prevalence of anemia among sexes, age groups, and races/ethnicities. The study estimated that an average of 5.6% of the U.S. population met the criteria for anemia and 1.5% for moderate-severe anemia during this 10-year period. High-risk groups such as pregnant women, elderly persons, women of reproductive age, non-Hispanic blacks, and Hispanics were identified, and relationships between multiple risk factors were examined. Rates of anemia in men increased monotonically with age, while that of women increased bimodally with peaks in age group 40-49 years and 80-85 years. The effect of risk factors was observed to compound. For instance, the prevalence of anemia in black women aged 80-85 years was 35.6%, 6.4 times higher than the population average. Moreover, anemia is a growing problem because of the increased prevalence of anemia (4.0% to 7.1%) and moderate-severe anemia (1.0% to 1.9%), which nearly doubled from 2003-2004 to 2011-2012. Thus, these results augment the current knowledge on anemia prevalence, severity, and distribution among subgroups in the US and raised anemia as an issue that requires urgent public health intervention.
Autoimmune cytopenias (AIC) following allogeneic hematopoietic stem cell transplantation (HSCT) may cause significant morbidity and mortality and are often challenging to treat. We present a case of ...a pediatric patient with primary myelofibrosis of infancy caused by VPS45 protein deficiency, who developed severe refractory hemolytic anemia and immune‐mediated thrombocytopenia 3.5 months following HSCT. After the failure of several treatments, he received daratumumab, an anti‐CD38 specific antibody, and demonstrated fast and sustained response. The only side effect was delayed recovery of humoral immunity. Daratumumab, by targeting antibody‐producing plasma cells, may be a valid treatment option for refractory post‐HSCT AIC.
Anemia in the elderly is a common finding that is associated with a poorer quality of life, worse outcomes, and increased mortality. While this entity is frequently overlooked, there is often an ...underlying cause that is correctable. Areas covered: In this review, we shed light on the prevalence of anemia in the elderly population, review the most common causes, particularly iron deficiency anemia and anemia of chronic disease, and describe the available treatment modalities. When a clear etiology for the anemia is ruled-out, the term unexplained anemia may be utilized; while still an under-explored field, one of the underlying pathophysiological mechanisms appears to be associated with an age-related inflammatory process. Expert commentary: Treating anemia secondary to nutritional deficiencies can be straightforward, but the management of the other types of anemia is not always the case. Treating anemia of chronic disease and anemia of chronic kidney disease may be limited by elevated levels of hepcidin and new promising treatments are still in pre-clinical and clinical trial phases. Caution should be employed when using erythropoiesis stimulating agents due to safety concerns, and when prescribing blood transfusion therapy, both of which lack the specific guidelines for use in the elderly.
During recent years, our understanding of the pathogenesis of inherited microcytic anemias has gained from the identification of several genes and proteins involved in systemic and cellular iron ...metabolism and heme syntheses. Numerous case reports illustrate that the implementation of these novel molecular discoveries in clinical practice has increased our understanding of the presentation, diagnosis, and management of these diseases. Integration of these insights into daily clinical practice will reduce delays in establishing a proper diagnosis, invasive and/or costly diagnostic tests, and unnecessary or even detrimental treatments. To assist the clinician, we developed evidence-based multidisciplinary guidelines on the management of rare microcytic anemias due to genetic disorders of iron metabolism and heme synthesis. These genetic disorders may present at all ages, and therefore these guidelines are relevant for pediatricians as well as clinicians who treat adults. This article summarizes these clinical practice guidelines and includes background on pathogenesis, conclusions, and recommendations and a diagnostic flowchart to facilitate using these guidelines in the clinical setting.
B
deficiency is the leading cause of megaloblastic anemia, and although more common in the elderly, can occur at any age. Clinical disease caused by B
deficiency usually connotes severe deficiency, ...resulting from a failure of the gastric or ileal phase of physiological B
absorption, best exemplified by the autoimmune disease pernicious anemia. There are many other causes of B
deficiency, which range from severe to mild. Mild deficiency usually results from failure to render food B
bioavailable or from dietary inadequacy. Although rarely resulting in megaloblastic anemia, mild deficiency may be associated with neurocognitive and other consequences. B
deficiency is best diagnosed using a combination of tests because none alone is completely reliable. The features of B
deficiency are variable and may be atypical. Timely diagnosis is important, and treatment is gratifying. Failure to diagnose B
deficiency can have dire consequences, usually neurological. This review is written from the perspective of a practicing hematologist.
BACKGROUND
The Jra antigen of JR blood group systems is located on ABCG2 and Jr(a–) subjects whose red blood cells (RBCs) lack ABCG2 have been identified mostly among the Japanese. Although anti‐Jra ...can cause fetal anemia, little is known regarding its mechanism.
STUDY DESIGN AND METHODS
We reviewed clinical courses of all reported cases with fetal anemia due to anti‐Jra. We analyzed the ABCG2 expressions of cord RBCs at various gestational ages. We examined the effects of sera containing anti‐Jra from three pregnancies with fetal anemia or monoclonal anti‐Jra on erythropoiesis and phagocytosis. We also examined epitopes of anti‐Jra.
RESULTS
Case series suggested that the majority of fetal anemia with anti‐Jra may not be progressive in the later gestational ages. ABCG2 expression levels of cord RBCs were significantly higher than those of adults and neonates with high individual variation and gradually decreased with advancing gestational ages. Anti‐Jra did not significantly impact erythroid colony formation, although we detected a tendency toward the suppression of erythroid burst‐forming unit formation by anti‐Jra using feline marrow cells. Anti‐Jra did not induce phagocytosis of sensitized RBCs by monocytes. While many anti‐Jra recognized the same regions as a monoclonal anti‐ABCG2, 5D3, epitopes of anti‐Jra did not correlate with the incidence of fetal anemia.
CONCLUSION
ABCG2 expression levels in cord RBCs are higher than those of adults, and the change of ABCG2 expression in erythroid lineage cells may influence the clinical course of fetal anemia with anti‐Jra, although we could not detect significant effects of anti‐Jra on erythroid colony formation or phagocytosis.
Sickle cell disease Ware, Russell E, Dr Prof; de Montalembert, Mariane, MD PhD; Tshilolo, Léon, Prof ...
The Lancet (British edition),
07/2017, Letnik:
390, Številka:
10091
Journal Article
Recenzirano
Summary Sickle cell disease is a common and life-threatening haematological disorder that affects millions of people worldwide. Abnormal sickle-shaped erythrocytes disrupt blood flow in small ...vessels, and this vaso-occlusion leads to distal tissue ischaemia and inflammation, with symptoms defining the acute painful sickle-cell crisis. Repeated sickling and ongoing haemolytic anaemia, even when subclinical, lead to parenchymal injury and chronic organ damage, causing substantial morbidity and early mortality. Currently available treatments are limited to transfusions and hydroxycarbamide, although stem cell transplantation might be a potentially curative therapy. Several new therapeutic options are in development, including gene therapy and gene editing. Recent advances include systematic universal screening for stroke risk, improved management of iron overload using oral chelators and non-invasive MRI measurements, and point-of-care diagnostic devices. Controversies include the role of haemolysis in sickle cell disease pathophysiology, optimal management of pregnancy, and strategies to prevent cerebrovascular disease.
Common fragile sites (CFSs) are genomic regions that are unstable under conditions of replicative stress. Although the characteristics of CFSs that render them vulnerable to stress are associated ...mainly with replication, the cellular pathways that protect CFSs during replication remain unclear. Here, we identify and describe a role for FANCD2 as a trans-acting facilitator of CFS replication, in the absence of exogenous replicative stress. In the absence of FANCD2, replication forks stall within the AT-rich fragility core of CFS, leading to dormant origin activation. Furthermore, FANCD2 deficiency is associated with DNA:RNA hybrid formation at CFS-FRA16D, and inhibition of DNA:RNA hybrid formation suppresses replication perturbation. In addition, we also found that FANCD2 reduces the number of potential sites of replication initiation. Our data demonstrate that FANCD2 protein is required to ensure efficient CFS replication and provide mechanistic insight into how FANCD2 regulates CFS stability.
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•FANCD2 regulates CFS replication even in the absence of replicative stress•Replication forks stall at endogenous CFS loci in FANCD2 patient-derived cells•DNA:RNA hybrid removal restores normal replication at CFS-FRA16D•FANCD2 deficiency is associated with altered replication initiation
Cells lacking proteins associated with the Fanconi anemia pathway are prone to chromosome breaks at CFSs. Madireddy et al. show that FANCD2 facilitates replication through repeat-rich genomic regions such as CFSs by ameliorating DNA:RNA hybrid accumulation and by influencing dormant origin firing, even during unperturbed replication.
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