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Background:
To study etiologies of anemia using an extensive laboratory analysis in general practices.
Method:
An extensive laboratory analysis was performed in blood of newly diagnosed anemia patients aged ≥50 years from the general population in the city of Dordrecht area, the Netherlands. Eight laboratory-orientated etiologies of anemia were...
Citations
... Anemia affects a third of the global population and is associated with increased morbidity and mortality [1][2][3]. The most common type of anemia is caused by congenital or acquired changes in iron metabolism that lead to decreased iron availability at the site of erythrocyte synthesis [4][5][6]. The decreased iron availability can result from absolute iron deficiency caused by blood loss, inadequate iron intake or malabsorption, and increased iron needs during pregnancy, which often leads to iron deficiency anemia (IDA) [1]. ...
Introduction: Traditional iron parameters often fail to distinguish the cause of iron-restricted anemia in patients without an obvious underlying cause. We evaluated whether an oral iron absorption test (OIAT) and hepcidin measurement could be useful diagnostic tests in these patients. Methods: We retrospectively analyzed data extracted from medical records of all patients who underwent an OIAT and hepcidin measurement, noting subsequent clinical diagnosis. Δ iron >15 µmol/L during the OIAT and hepcidin level below the median (or suppressed ≤0.5 nM) were considered appropriate. Results: Thirty-nine adult patients were included in the study. Sixteen patients with adequate OIAT had suppressed hepcidin levels indicative of classical iron-deficiency anemia (IDA); 59% of patients had abnormal OIAT. In this group, most patients with low hepcidin levels had anemia associated with abnormalities in the gastrointestinal tract, whereas 83.3% patients with high hepcidin levels had iron-refractory iron deficiency anemia (IRIDA), confirmed by genetic testing. Finally, transferrin/log ferritin ratio accurately identified patients with suppressed hepcidin: AUC 0.98 [95% CI: 0.95–1.02], P < 0.001. Conclusion: OIAT differentiates between classical IDA and other types of anemia caused by abnormalities in iron absorption or systemic iron availability. Additionally, elevated hepcidin in patients with oral iron malabsorption could indicate IRIDA.
... In clinical practice, the aetiological diagnosis of anaemia depends on a "framework approach", which is based on clinical information and laboratory test results. The latter include a wide range of costly and sophisticated haematology and biochemistry analysis [22]. In low-resource settings (LRS), the limited availability of diagnostic tests for anaemia poses a challenge in accurately interpreting and effectively managing anaemia, particularly in cases where multiple causes may be involved [23,24]. ...
Introduction
In low-resource settings, anaemia is a very common condition. Identification of anaemia aetiologies remains challenging due to the lack of diagnostic tools and expertise. We aimed to improve anaemia diagnostics using peripheral blood smear (PBS) with remote interpretation in people living with HIV (PLHIV) with moderate to severe anaemia.
Methods
We conducted a prospective study nested within the Kilombero and Ulanga Antiretroviral Cohort, including non-pregnant PLHIV aged ≥18 years presenting with moderate (haemoglobin 7.0–9.9 g/dl) or severe (<7.0 g/dl) anaemia at any visit from January 2019 to December 2020. For each participant, ten PBS images, full blood count and clinical details were shared with a haematologist for remote interpretation (enhanced care). Identification of anaemia etiologies and potential impact on treatment was compared between enhanced and standard care.
Results
Among 400 PLHIV with moderate to severe anaemia, 349 (87%) were female, median age was 40 years (interquartile range (IQR) 35–46)), 65 (17%) had a body mass index <18.5 kg/m ² , 215 (54%) had HIV WHO stage III/IV, 79 (20%) had a CD4 cell count <200 cells/μl and 317 (89%) had HIV viral load <100 copies/ml. Severe anaemia was diagnosed in 84 (21%). Suspected multiple aetiologies were documented more frequently by enhanced care compared to standard care 267 (67%) vs 20 (5%); p<0.001. Suspected iron deficiency was the most frequent aetiology (n = 337; 84%), followed by chronic disease (n = 199; 50%), folate/vitamin B12 deficiency (n = 78; 20%) and haemoglobinopathy (n = 83; 21%). In 272 participants (68%), enhanced care revealed additional clinically relevant findings with impact on the treatment recommendation.
Conclusion
Remote interpretation of PBS combined with clinical information and blood cell count results can provide insights to the suspected aetiological diagnosis of moderate and severe anaemia in rural low-resource settings and impact specific treatment.
... 7,10,11 Er zijn aanwijzingen dat een uitgebreider analyseprotocol leidt tot een hoger percentage correcte diagnoses. 8,9,12 Daarbij zijn er ook aanwijzingen dat dit uiteindelijk een kosteneffectieve aanpak is. 13 ...
This commentary discusses the prevalence and causes of anemia in primary care in the Netherlands and the role of laboratory diagnostics in determining the cause of anemia. There are indications that guidelines in primary care regarding anemia are insufficiently followed; there are also indications that the correct laboratory measurements are requested too limited (under-diagnosis). A possible solution lies in the introduction of reflective testing, in which the laboratory specialist has additional diagnostic laboratory tests performed on the basis of the laboratory results and specific characteristics of the patient. Reflective testing is in contrast to reflex testing; in reflex testing, laboratory measurements are added automatically using a simple flowchart. In the future, Artificial Intelligence solutions could play a role in determining the most optimal laboratory diagnostic strategy for the diagnosis of anemia in primary care.
... Another study described that the severity of anemia was predictive for the underlying cause [98]: mild anemia was more frequently caused by chronic disease whereas severe anemia was more common with iron deficiency. These observations illustrate that the results from scientific studies of anemia can depend on the definition of anemia [95]. ...
... Taken together, the observations referred to above illustrate the importance of clearly stating the definition of anemia used in clinical studies. The use of the WHO definition is important to allow comparisons between different studies, but additional analyses using/comparing different definitions may also be useful [97,98]. ...
... The cause of anemia in elderly individuals has also been investigated in other studies [99,102,103], and the overall results show that a relatively large number of elderly patients with anemia has an unknown cause after a limited evaluation based on clinical examination and blood samples (Table 4). Table 4. Causes of anemia in elderly patients, a summary of the results from selected previous studies [98,99,102,103]. For a detailed discussion with additional references see Sections 3.5 and 3.6. ...
Anemia and systemic signs of inflammation are common in elderly individuals and are associated with decreased survival. The common biological context for these two states is then the hallmarks of aging, i.e., genomic instability, telomere shortening, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion and altered intercellular communication. Such aging-associated alterations of hematopoietic stem cells are probably caused by complex mechanisms and depend on both the aging of hematopoietic (stem) cells and on the supporting stromal cells. The function of inflammatory or immunocompetent cells is also altered by aging. The intracellular signaling initiated by soluble proinflammatory mediators (e.g., IL1, IL6 and TNFα) is altered during aging and contributes to the development of both the inhibition of erythropoiesis with anemia as well as to the development of the acute-phase reaction as a systemic sign of inflammation with increased CRP levels. Both anemia and increased CRP levels are associated with decreased overall survival and increased cardiovascular mortality. The handling of elderly patients with inflammation and/or anemia should in our opinion be individualized; all of them should have a limited evaluation with regard to the cause of the abnormalities, but the extent of additional and especially invasive diagnostic evaluation should be based on an overall clinical evaluation and the possible therapeutic consequences.
... This suggests that in some anemic subjects classified as deficient, the coexisting non-deficiency factor (e.g., renal function impairment or inflammation) may play a greater role in the etiopathogenesis of anemia than the deficiency itself. In the study performed in the city of Dordrecht area, the Netherlands, performed on the group of over 4000 anemic persons aged >50, the anemia related to multiple causes was found in 22% of subjects and the coexistence of vitamin B12 or folate deficiency with other etiologies was the most common [36]. These results are consistent with our observation, where the coexistence of non-deficient etiology was more often observed in vitamin B12 or folate deficiency compared to iron deficiency. ...
Vitamin B12, folate, iron deficiency (IDA), chronic kidney disease (CKD), and anemia of inflammation (AI) are among the main causes of anemia in the elderly. WHO criteria of nutritional deficiencies neglect aging-related changes in absorption, metabolism, and utilization of nutrients. Age-specific criteria for the diagnosis of functional nutritional deficiency related to anemia are necessary. We examined the nationally representative sample of Polish seniors. Complete blood count, serum iron, ferritin, vitamin B12, folate, and renal parameters were assessed in 3452 (1632 women, 1820 men) participants aged above 64. Cut-off points for nutritional deficiencies were determined based on the WHO criteria (method-A), lower 2.5 percentile of the studied population (method-B), and receiver operating characteristic (ROC) analysis (method-C). Method-A leads to an overestimation of the prevalence of vitamin B12 and folate deficiency, while method-B to their underestimation with over 50% of unexplained anemia. Based on method-C, anemia was classified as nutritional in 55.9%. In 22.3% of cases, reasons for anemia remained unexplained, the other 21.8% were related to CKD or AI. Mild cases were less common in IDA, and more common in non-deficiency anemia. Serum folate had an insignificant impact on anemia. It is necessary to adopt the age-specific criteria for nutrient deficiency in an old population.
... The original cohort study was designed by general practitioners, clinical chemists and internists (10). Patient data were selected from a database with patients from general practice. ...
... Both panels consisted of an extensive laboratory work-up for all patients at the time of anaemia diagnosis; i.e. measurement of haemoglobin, MCV, reticulocyte count, thrombocyte count, leucocyte count, lactate dehydrogenase, vitamin B12, folic acid, ferritin, transferrin, serum iron and creatinine (sidenote: creatinine was only included in one of two panels). More detailed information about the study population can be found in a previously published study (10). The project operated from 1 February 2007 until 1 February 2017. ...
... Each definition was based on literature and the Dutch general practitioners' guideline of anaemia (2,3,(11)(12)(13)(14). The definitions are added as Supplemental Data 1 (10). The definitions were strictly applied, which made it possible to have multiple aetiologies in one patient. ...
Background
Anemia can be categorized into micro-, normo- or macrocytic anemia based on the mean corpuscular volume (MCV). This categorization might help to define the etiology of anemia.
Methods
The cohort consisted of patients newly diagnosed with anaemia in primary care. Seven aetiologies of anaemia were defined, based on an extensive laboratory protocol. Two assumptions were tested: (i) MCV <80 fl (microcytic) excludes vitamin B12 deficiency, folic acid deficiency, suspected haemolysis and suspected bone marrow disease as anaemia aetiology. (ii) MCV >100 fl (macrocytic) excludes iron deficiency anaemia, anaemia of chronic disease and renal anaemia as anaemia aetiology.
Results
Data of 4129 patients were analysed. One anaemia aetiology could be assigned to 2422 (59%) patients, more than one anaemia aetiology to 888 (22%) patients and uncertainty regarding the aetiology remained in 819 (20%) patients. MCV values were within the normal range in 3505 patients (85%). In 59 of 365 microcytic patients (16%), the anaemia aetiology was not in accordance with the first assumption. In 233 of 259 macrocytic patients (90%), the anaemia aetiology was not in accordance with the second assumption.
Conclusions
Anaemia aetiologies might be ruled out incorrectly if MCV guided classification is used as a first step in the diagnostic work-up of anaemia. We recommend using a broader set of laboratory tests, independent of MCV.
Iron is an essential micronutrient for life. In mammals, dietary iron is primarily absorbed in the small intestine. Currently, the impacts of dietary iron on the taxonomic structure and function of the gut microbiome and reciprocal effects on the animal host are not well understood. Here, we establish a mouse model of low-iron challenge in which intestinal biomarkers and reduced fecal iron reveal iron stress while serum iron and mouse behavioral markers indicate maintenance of iron homeostasis. We show that the diversity of the gut microbiome in conventional C57BL/6 mice changes dramatically during two-weeks on a low-iron diet. We also show the effects of a low-iron diet on microbiome diversity are long-lasting and not easily recovered when iron is returned to the diet. Finally, after optimizing taxon association methods, we show that some bacteria are unable to fully recover after the low-iron challenge and appear to be extirpated from the gut entirely. In particular, OTUs from the Prevotellaceae and Porphyromonadaceae families and Bacteroidales order are highly sensitive to low-iron conditions, while other seemingly insensitive OTUs recover. These results provide new insights into the iron requirements of gut microbiome members and add to the growing understanding of mammalian iron cycling.
IMPORTANCE
All cells need iron. Both too much iron and too little lead to diseases and unwanted outcomes. Although the impact of dietary iron on human cells and tissues has been well studied, there is currently a lack of understanding about how different levels of iron influence the abundant and diverse members of the human microbiome. This study develops a well-characterized mouse model for studying low-iron levels and identifies key groups of bacteria that are most affected. We found that the microbiome undergoes large changes when iron is removed from the diet but that many individual bacteria are able to rebound when iron levels are changed by to normal. That said, a select few members, referred to as “iron-sensitive” bacteria seem to be lost. This study begins to identify individual members of the mammalian microbiome most affected by changes in dietary iron levels.
