Guidelines on the diagnosis and treatment of iron deficiency (ID) vary widely across indications.
We reviewed all available guidelines on the management of ID worldwide.
A literature search was ...conducted in PubMed, Cochrane, and EMBASE and in main professional association websites, limited to documents published between 1 January 2004 and 30 June 2014.
Of 127 guidelines identified, 29 were selected, involving 29 professional associations and issued from the United States (n = 8), Europe (n = 6), Britain (n = 4), Canada (n = 3), international organizations (n = 2), France (n = 2), Poland (n = 1), Australia (n = 1), Mexico (n = 1), and Japan (n = 1). A total of 22 and 27 guidelines provided recommendations on diagnosis and treatment of ID, respectively. To define ID, all guidelines recommended a concentration for serum ferritin. One-half of them (10 of 22) proposed transferrin saturation (TSAT) as an alternative or complementary diagnostic test. To treat ID, most of the guidelines (18 of 27) recommended preferentially the oral route if possible, particularly in children and in women in the pre- or postpregnancy period. Iron supplementation should be administered intravenously according to 13 of 27 guidelines, particularly in patients with chronic kidney disease (CKD) (n = 7) and chemotherapy-induced anemia (n = 5). Treatment targets for ID included an increase in hemoglobin concentrations to 10-12 g/dL or normalization (n = 8) and serum ferritin >100 μg/L (n = 7) or 200 μg/L (n = 4). For the latter, in some situations, such as CKD, ferritin concentrations should not exceed 500 μg/L (n = 5) or 800 μg/L (n = 5). Only 9 guidelines recommended TSAT as a target, proposing various thresholds ranging from 20% to 50%.
It appears that for the diagnosis of ID, a cutoff of 100 μg/L for serum ferritin concentration should be considered in most conditions and 20% for TSAT, except in particular situations, including young healthy women with heavy menstrual flow. New indications of intravenous iron supplementation are emerging.
Fanconi anaemia (FA) is a recessive disorder characterized by genomic instability, congenital abnormalities, cancer predisposition and bone marrow (BM) failure. However, the pathogenesis of FA is not ...fully understood partly due to the limitations of current disease models. Here, we derive integration free-induced pluripotent stem cells (iPSCs) from an FA patient without genetic complementation and report in situ gene correction in FA-iPSCs as well as the generation of isogenic FANCA-deficient human embryonic stem cell (ESC) lines. FA cellular phenotypes are recapitulated in iPSCs/ESCs and their adult stem/progenitor cell derivatives. By using isogenic pathogenic mutation-free controls as well as cellular and genomic tools, our model serves to facilitate the discovery of novel disease features. We validate our model as a drug-screening platform by identifying several compounds that improve hematopoietic differentiation of FA-iPSCs. These compounds are also able to rescue the hematopoietic phenotype of FA patient BM cells.
Summary The inherited bone marrow failure syndromes (IBMFS) are a rare yet clinically important cause of neonatal hematological and non-hematological manifestations. Many of these syndromes, such as ...Fanconi anemia, dyskeratosis congenita and Diamond–Blackfan anemia, confer risks of multiple medical complications later in life, including an increased risk of cancer. Some IBMFS may present with cytopenias in the neonatal period whereas others may present only with congenital physical abnormalities and progress to pancytopenia later in life. A thorough family history and detailed physical examination are integral to the work-up of any neonate in whom there is a high index of suspicion for an IBMFS. Correct detection and diagnosis of these disorders is important for appropriate long-term medical surveillance and counseling not only for the patient but also for appropriate genetic counselling of their families regarding recurrence risks in future children and generations.
β-Thalassemia and sickle cell disease (SCD) are the world’s two most widely disseminated hereditary hemoglobinopathies. β-Thalassemia originated in the Mediterranean, Middle Eastern, and Asian ...regions, and SCD originated in central Africa. However, subsequent population migration means that these two diseases are now global and thus constitute a growing health problem in many countries. Despite remarkable improvements in medical care for patients with β-hemoglobinopathies, there is still only one definitive treatment option: allogeneic hematopoietic stem cell (HSC) transplantation. The development of gene therapy for β-hemoglobinopathies has been justified by (1) the limited availability of human leukocyte antigen (HLA)-identical donors, (2) the narrow window of application of HSC transplantation to the youngest patients, and (3) recent advances in HSC-based gene therapy. The huge ongoing efforts in translational medicine and the high number of related publications show that gene therapy has the potential to become the treatment of choice for patients who lack either an HLA genoidentical sibling or an alternative, medically acceptable donor. In this dynamic scientific context, we first summarize the main steps toward clinical translation of this therapeutic approach and then discuss novel lentiviral- and genome editing-based treatment strategies for β-hemoglobinopathies.
In this review, Cavazzana et al. summarize the main steps toward clinical translation of gene addition approaches for β-thalassemia and sickle cell disease and discuss novel lentiviral- and genome editing-based treatment strategies for β-hemoglobinopathies.
Anemia is common in the intensive care unit, and may be associated with adverse consequences. However, current options for correcting anemia are not without problems and presently lack convincing ...efficacy for improving survival in critically ill patients. In this article we review normal red blood cell physiology; etiologies of anemia in the intensive care unit; its association with adverse outcomes; and the risks, benefits, and efficacy of various management strategies, including blood transfusion, erythropoietin, blood substitutes, iron therapy, and minimization of diagnostic phlebotomy.
Equine infectious anemia (EIA), a disease caused by equine infectious anemia virus (EIAV), is considered an obstacle to the development of the horse industry. There is no treatment or vaccine ...available for EIA, and its pathogenesis, as well as the immune response against the virus, is not fully understood. Therefore, an immunohistochemistry assay was developed for the detection of viral antigens in tissues of equids naturally infected with EIAV. Sections of organs of six equids from Apodi–RN, Brazil, that tested positive for EIA by serological tests (ELISA and AGID) were fixed in 10% formalin solution and embedded in paraffin. Immunohistochemistry was performed using a polyclonal anti-EIAV antibody. EIAV antigens were observed in red spleen pulp cells and hepatic sinusoids, as well as bronchiolar and alveolar epithelial cells of the lungs and proximal and distal tubules of the kidneys. The presence of EIAV in the spleen and liver was expected due to viral tropism by macrophages, which are abundantly present in these organs. However, EIAV was also found in lung and kidney epithelial cells, indicating that the virus infects cell types other than macrophages. In conclusion, the immunohistochemical assay standardized in this study was able to detect EIAV antigens in spleen, liver, kidney and lung cells from naturally infected EIAV equids. Immunostaining observed in the spleen confirms viral tropism by mononuclear phagocytes; however, the presence of EIAV in lung and kidney epithelial cells indicates that virus may be eliminated in urine and/or oronasal secretions, suggesting new routes for viral excretion.
Recent advances in diagnosis and treatment of inherited bone marrow failure syndromes (IBMFS) have significantly improved disease understanding and patient outcomes. Still, IBMFS present clinical ...challenges that require further progress. This review aims to provide an overview of the current state of diagnosis and treatment modalities of the major IBMFS seen in paediatrics and present areas of prioritization for future research.
Haematopoietic cell transplantation (HCT) for IBMFS has greatly improved in recent years, shifting the research and clinical focus towards cancer predispositions and adverse effects of treatment. Each year, additional novel genes and pathogenic variants are described, and genotype-phenotype mapping becomes more sophisticated. Moreover, novel therapeutics exploring disease-specific mechanisms show promise to complement HCT and treat patients who cannot undergo current treatment options.
Research on IBMFS should have short-term and long-term goals. Immediate challenges include solidifying diagnostic and treatment guidelines, cancer detection and treatment, and continued optimization of HCT. Long-term goals should emphasize genotype-phenotype mapping, genetic screening tools and gene-targeted therapy.
In many elderly patients with anemia, a specific cause cannot be identified. This study investigates whether erythropoietin levels are inappropriately low in these cases of "anemia of unknown ...etiology" and whether this trend persists after accounting for confounders.
This study includes all anemic patients over 60 years old who had erythropoietin measured between 2005 and 2013 at a single center. Three independent reviewers used defined criteria to assign each patient's anemia to one of ten etiologies: chronic kidney disease, iron deficiency, chronic disease, confirmed myelodysplastic syndrome (MDS), suspected MDS, vitamin B12 deficiency, folate deficiency, anemia of unknown etiology, other etiology, or multifactorial etiology. Iron deficiency anemia served as the comparison group in all analyses. We used linear regression to model the relationship between erythropoietin and the presence of each etiology, sequentially adding terms to the model to account for the hemoglobin concentration, estimated glomerular filtration rate (eGFR) and Charlson Comorbidity Index.
A total of 570 patients met the inclusion criteria. Linear regression analysis showed that erythropoietin levels in chronic kidney disease, anemia of chronic disease and anemia of unknown etiology were lower by 48%, 46% and 27%, respectively, compared to iron deficiency anemia even after adjusting for hemoglobin, eGFR and comorbidities.
We have shown that erythropoietin levels are inappropriately low in anemia of unknown etiology, even after adjusting for confounders. This suggests that decreased erythropoietin production may play a key role in the pathogenesis of anemia of unknown etiology.
Abstract
Objective.
To evaluate the prevalence of anemia and iron deficiency (ID) among patients with inflammatory bowel disease (IBD) in the Scandinavian countries.
Material and methods.
A ...cross-sectional study including 429 IBD patients from six centers in Denmark, Norway and Sweden. Patients were screened for anemia and ID. Each center included ∼5% of their IBD cohort. Patients were consecutively seen in the outpatient clinic, regardless of disease activity and whether the visits were scheduled or not.
Results.
The overall prevalence of anemia was 19% (95% CI: 16-23%). The prevalence was higher among patients with Crohn's disease than among patients with ulcerative colitis (p = 0.01). The etiology of anemia was as follows: iron deficiency anemia (20%), anemia of chronic disease (12%), and both conditions (68%). Less than 5% had folate acid or vitamin B12 deficiency. ID was found in 35% (CI: 31-40%) of the patients.
Conclusions.
Anemia was present in every fifth IBD patient and ID in every third IBD patient.
PDF
