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Anaemia in the elderly
La anemia del anciano
Susana Gómez Ramíreza,b, Ángel Francisco Remacha Sevillaa,c, Manuel Muñoz Gómeza,d,
Corresponding author
mmunoz@uma.es

Corresponding author.
a Anemia Working Group España (AWGE), Spain
b Unidad de Gestión Clínica de Medicina Interna, Hospital Clínico Virgen de la Victoria, Málaga, Spain
c Servicio de Hematología, Hospital Sant Pau, Barcelona, Spain
d Medicina Transfusional Perioperatoria, Facultad de Medicina, Universidad de Málaga, Málaga, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleDisplayedQuote" id="dsq0005"><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Growing old is like climbing a great mountain&#46; While you climb&#44; your strength grows weak&#44; but the gaze is freer&#44; the view more clear and serene</p><span class="elsevierStyleSource"><span class="elsevierStyleSmallCaps">Ingmar Bergman</span></span></span></p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0010" class="elsevierStylePara elsevierViewall">The average life expectancy has increased drastically over the last century &#40;from &#8776;60 years in 1900 to &#8776;80 years in 2015&#41; and is estimated to increase further in the future&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">1</span></a> In the European Union&#44; the proportion of individuals &#8805;80 years will triple between 2011 and 2060&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">2</span></a> With age there is an inevitable deterioration of the organic functionality &#40;ageing&#41; that eventually leads to death&#46; Age is also a risk factor for common processes&#44; whether diagnosed or not&#44; such as cardiovascular disease&#44; cancer&#44; diabetes or Alzheimer&#39;s disease&#44; which increase the risk of mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">1</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Factors responsible for the phenotypic changes leading to the loss of physiological reserve&#44; organic failure and reduction of the functionality have a role in the ageing process&#46; The sum of these factors would give rise to the clinical features in the elderly&#58; frailty&#44; anaemia&#44; malnutrition and poor immune response&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">1</span></a> Whether anaemia is an independent risk factor for functional impairment&#44; a surrogate marker of a worse health status or simply an additional comorbidity&#44; is something that we still do not know&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">A better understanding of the molecular basis of ageing would facilitate the development of interventions that&#44; if applied early&#44; could prevent&#44; delay&#44; alleviate or even reverse some of the diseases related to ageing&#44; thereby gaining years of independent living&#46; That is&#44; we would not only add &#8220;years to life&#8221;&#44; but also &#8220;life to years&#8221;&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Definition and prevalence of anaemia in the elderly</span><p id="par0025" class="elsevierStylePara elsevierViewall">According to the World Health Organization &#40;WHO&#41;&#44; the concentration of haemoglobin &#40;Hb&#41; that defines the presence of anaemia in the elderly would be &#60;13<span class="elsevierStyleHsp" style=""></span>g&#47;dl in men and &#60;12<span class="elsevierStyleHsp" style=""></span>g&#47;dl in women&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">3</span></a> With these definitions&#44; between 1993 and 2005 anaemia affected 24&#37; of the world&#39;s elderly &#40;164 million individuals&#41;&#44; although with important regional differences&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">4</span></a> However&#44; there are authors who question its validity in the elderly&#44; in whom an Hb value near the lower limit of normality could be associated with a worse physical and cognitive state&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">5</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">At the <span class="elsevierStyleItalic">Third US National Health and Nutrition Examination Survey</span> &#40;NHANES III&#44; Phases 1 and 2&#44; 1988&#8211;1994&#59; 26&#44;372 individuals&#41;&#44; the prevalence of anaemia in individuals &#8805;65 years of age progressively increased with age &#40;13&#37; in individuals aged 75&#8211;84 years&#44; 23&#37; in the 85 years old or more&#41; and was higher among men&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">6</span></a> In the recent EMPIRE study in Portugal&#44; the prevalence in 1617 individuals &#62;65 years old was also higher in men &#40;22&#46;2&#37;&#41; than in women &#40;19&#46;9&#37;&#41; and increased with age &#40;17&#46;3&#37; in 65&#8211;79 years&#44; 31&#46;4&#37; in &#8805;80 years&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">7</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The different prevalence of anaemia according to sex may reflect differences in incidence&#46; In an elderly population of Olmsted County &#40;Minnesota&#41;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>618&#44; the annual incidence increased with age and was higher in men &#40;90&#46;3 per 1000&#41; than in women &#40;69&#46;1 per 1000&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">8</span></a> In 465 cases &#40;75&#37;&#41; anaemia was detected during hospital admission&#44; although anaemia was the cause of hospitalization in only 57 cases&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">8</span></a> In contrast&#44; in the region of Piedmont &#40;Italy&#41;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>529&#44; the annual incidence of anaemia and mild anaemia were 24&#46;2 and 22&#46;5 per 1000&#44; respectively&#44; with no differences between sexes&#44; but increasing with age &#40;4&#46;9 per 1000 in the 65&#8211;69 years group&#44; 72&#46;4 per 1000 in the 80&#8211;84 years group&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">9</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">In a meta-analysis of 34 epidemiological studies &#40;85&#44;409 elderly&#41;&#44; the mean prevalence was 17&#37;&#44; but fell to 6&#37; when anaemia was defined by an Hb<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>11<span class="elsevierStyleHsp" style=""></span>g&#47;dl&#44; indicating that it was mild in most cases&#46; The prevalence was lower among the elderly living in the community &#40;12&#37;&#41; than those living in nursing homes &#40;47&#37;&#41; or that were hospitalized &#40;40&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">10</span></a> In the InCHIANTI study&#44; the prevalence of anaemia in the Italian population &#62;65 years of age was 11&#37;&#44; rising to 48&#8211;60&#37; in hospitalized individuals&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">11</span></a> In a series of &#62;300&#44;000 elderly males admitted for non-cardiac surgery in the United States&#44; 43&#37; had a haematocrit &#60;39&#37;&#44; but only &#60;33&#37; in 15&#37; of cases&#44; again indicating that anaemia was mild in most cases&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">12</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">In Spain&#44; a multicenter study revealed that the prevalence of anaemia in elderly who had undergone surgery<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1687 ranged from 14&#37; in prostate surgery to 61&#37; in colorectal cancer&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">13</span></a> Among non-operated hospitalized patients &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>796&#41; the mean prevalence was 57&#37; &#40;32&#37; mild&#44; 20&#37; moderate&#44; 5&#37; severe&#41;&#44; although there were differences according to the department&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">14</span></a> Among the outpatient population&#44; a study in the Huesca Sector &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>32&#44;666&#59; 2011&#8211;2015&#41; found that the prevalence of anaemia increased with age from 80 years onwards&#44; being higher in men &#40;16 and 12&#37; among the 80&#8211;89 years old&#59; 31&#46;6 and 22&#46;4&#37; in &#62;90 years old&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">15</span></a> The total Spanish population will decrease from 46&#44;507&#44;760 in 2014 to 45&#44;484&#44;908 in 2029&#44; while the population &#8805;65 years of age will grow from 8&#44;442&#44;887 &#40;18&#46;2&#37;&#41; to 11&#44;275&#44;805 &#40;24&#46;8&#37;&#41; &#40;<a href="http://www.ine.es/prensa/prensa.htm">www&#46;ine&#46;es&#47;prensa&#47;prensa&#46;htm</a>&#41;&#46; Extrapolating data from these studies&#44; the number of anaemic elderly will increase from 1100&#44;000 in 2014 to 1500&#44;000 in 2029 &#40;&#43;36&#37;&#41;&#44; which will be a significant burden on our health system&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Consequences of anaemia in the elderly</span><p id="par0050" class="elsevierStylePara elsevierViewall">Anaemia reduces physical capacity and muscle strength in the elderly&#44; decreasing mobility and quality of life&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">16</span></a> In addition&#44; it increases the risk of fatigue&#44; depression&#44; dementia&#44; hospitalization &#40;due to exacerbations of intercurrent disease&#44; falls&#41; or admission to nursing homes &#40;due to exacerbation of functional deterioration&#41; and mortality &#40;especially if accompanied by other disorders such as heart or kidney failure&#44; high blood pressure or diabetes&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0385"><span class="elsevierStyleSup">17&#44;18</span></a> In a meta-analysis of 24 studies &#40;949&#44;445 patients&#41;&#44; preoperative anaemia &#40;39&#37;&#41; showed an independent association with an increased risk of transfusion&#44; postoperative complications and mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">19</span></a> For this reason&#44; the detection&#44; classification and treatment of anaemia in the elderly should be a priority objective for the health system&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Hematin deficiencies without anaemia can also have consequences in the elderly&#46; Individuals with hematinic deficiency without anaemia may develop symptoms such as fatigue or decreased exercise tolerance&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">20</span></a> In congestive heart failure&#44; iron deficiency is associated with decreased physical performance and quality of life and with increased mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">21</span></a> Iron deficiency can cause secondary thrombocytosis in renal failure&#44; cancer or inflammatory bowel disease&#44; increasing the risk of thromboembolic phenomena&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">22</span></a> Generally&#44; preclinical or moderate vitamin B deficiency<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">12</span></a> &#40;5&#8211;20&#37; of the elderly population&#41; is not accompanied by anaemia but may contribute to cognitive impairment and increased thrombotic risk&#46;<a class="elsevierStyleCrossRefs" href="#bib0415"><span class="elsevierStyleSup">23&#44;24</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Causes of anaemia in the elderly</span><p id="par0060" class="elsevierStylePara elsevierViewall">Anaemia in the elderly usually has a multifactorial origin&#59; all pathophysiological mechanisms are possible and many of them are simultaneous&#46; In the NAHNES III study&#44; nutritional deficiencies were responsible for 34&#37; of the cases&#44; while chronic diseases&#44; with and without renal failure&#44; accounted for another 33&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">7</span></a> In 33&#37; of cases&#44; it was not possible to identify the aetiology &#40;unexplained anaemia in the elderly &#91;UAE&#93;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">7</span></a> The high prevalence of UAE &#40;25&#8211;45&#37;&#41; in large epidemiological studies on thousands of individuals could simply reflect the use of a limited number of diagnostic tests&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">17</span></a> When exhaustive studies &#40;necessarily with much fewer cases&#41; are carried out&#44; only 15&#37; of the anaemias are classified as UAE&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">25</span></a></p><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Nutrient deficiency</span><p id="par0065" class="elsevierStylePara elsevierViewall">Erythropoiesis needs about 20&#8211;25<span class="elsevierStyleHsp" style=""></span>mg of <span class="elsevierStyleItalic">iron</span> per day&#44; 99&#37; of which comes from Hb recycling of red blood cells in macrophages&#46; Intestinal absorption only contributes 1&#37; and compensates the daily losses&#46; When the absorption decreases or the losses increase &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>A&#41;&#44; iron deposits are used&#44; decreasing progressively&#46; This causes a progressive iron deficiency and finally iron deficiency anaemia &#40;IDA&#41;&#44; when enough iron is not available to synthesize Hb&#46;<a class="elsevierStyleCrossRefs" href="#bib0430"><span class="elsevierStyleSup">26&#44;27</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Vitamin B</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">12</span></span> is essential to produce red blood cells and the functioning of the nervous system&#46; Its absorption depends on the intrinsic factor &#40;synthesized by the gastric parietal cells&#41;&#44; and is produced by the &#8220;cubam receptor&#8221; of the distal ileum&#46; Decreased absorption of vitamin B<span class="elsevierStyleInf">12</span> leads to its deficiency &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>B&#41;&#46; The most common cause is the loss of the intrinsic factor secondary to autoimmune atrophic gastritis&#44; which may be found to be anti-intrinsic factor Ab and anti-gastric parietal cell Ab &#40;&#8220;pernicious anaemia&#8221; or Adisson-Biermer&#39;s anaemia&#41;&#46; The immune response is directed against the gastric H<span class="elsevierStyleSup">&#43;</span>K<span class="elsevierStyleSup">&#43;</span>-ATPase and is responsible for associated achlorhydria&#46; Autoimmune gastritis can cause malabsorption of iron&#59; with subsequent compromise of vitamin B absorption<span class="elsevierStyleInf">12</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">28</span></a> Lighter forms of atrophic gastritis&#44; with hypochlorhydria and food-bound vitamin malabsorption &#40;<span class="elsevierStyleItalic">food-cobalamin malabsorption</span>&#41;&#44; would lead to preclinical or moderate vitamin B deficiency<span class="elsevierStyleInf">12</span>&#46;<a class="elsevierStyleCrossRefs" href="#bib0415"><span class="elsevierStyleSup">23&#44;24&#44;28</span></a> Less common causes include absence of ileal absorption areas &#40;due to inflammatory enteritis or surgical resection&#41;&#44; blind loop syndrome&#44; chronic pancreatitis&#44; and use of certain drugs&#44; such as metformin &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>B&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">28</span></a><span class="elsevierStyleItalic">Folate</span> deficiency is more uncommon and may be caused by insufficient intake&#44; absorption problems or drug interactions &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>C&#41;&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Vitamin D</span> reduces the release of proinflammatory cytokines and hepcidin synthesis&#44; and its deficiency has been associated with chronic inflammatory anaemia &#40;CIA&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">29</span></a> Individuals with concentrations of 25OHD<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>20<span class="elsevierStyleHsp" style=""></span>ng&#47;ml are more likely to have anemia&#46;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">30</span></a> In healthy volunteers&#44; oral administration of vitamin<span class="elsevierStyleHsp" style=""></span>D<span class="elsevierStyleInf">2</span> &#40;100&#44;000<span class="elsevierStyleHsp" style=""></span>IU&#41; increased levels of 25OHD &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41; and reduced hepcidin by 34&#37; during the following 24<span class="elsevierStyleHsp" style=""></span>h &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#44; confirming the regulatory role of vitamin D on the hepcidin-ferroportin axis&#46;<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">31</span></a> It is important to pay attention to <span class="elsevierStyleItalic">vitamin B</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">6</span></span>&#44; since it is involved in the synthesis of the heme group&#44; and <span class="elsevierStyleItalic">vitamin C</span>&#44; which facilitates cellular uptake of transferrin-bound iron&#46;<a class="elsevierStyleCrossRefs" href="#bib0430"><span class="elsevierStyleSup">26&#44;27&#44;32</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Chronic inflammatory processes</span><p id="par0080" class="elsevierStylePara elsevierViewall">CIA is related to the pathophysiological changes of the underlying disease &#40;neoplastic&#44; infectious or inflammatory processes&#41; and is usually moderate and normochromic-normocytic&#46; Some proinflammatory cytokines &#40;tumour necrosis factor-alpha&#44; interleukin-1&#44; interleukin-6 and interferon-gamma&#41; are involved in its development&#44; causing a triple effect&#58; &#40;1&#41; decreased production of erythropoietin &#40;EPO&#41; in response to decreased erythrocyte mass&#59; &#40;2&#41; inhibition of the effect of EPO on erythroid precursors&#44; and &#40;3&#41; poor use of iron by inhibiting its intestinal absorption and reducing its release from macrophages &#40;iron sequestration&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0430"><span class="elsevierStyleSup">26&#44;27&#44;33</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Renal failure</span><p id="par0085" class="elsevierStylePara elsevierViewall">It is one of the most common causes of anaemia in the elderly&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">7</span></a> Even moderate renal failures &#40;estimated glomerular filtration rate &#91;EGFR&#93;<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>60<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#41; may develop with inadequate synthesis of EPO and anaemia&#44; which in turn may worsen the clinical course of other processes&#44; especially cardiac and respiratory&#46; This anaemia usually responds to relatively low doses of erythropoiesis stimulating agents &#40;ESAs&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">34</span></a> Some comorbidities and treatments may increase the risk of renal failure &#40;hypertension&#44; diabetes&#44; nonsteroidal anti-inflammatory drugs&#41; and&#47;or reduce the synthesis of EPO &#40;angiotensin-converting enzyme inhibitors&#41;&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Myelodysplastic syndromes</span><p id="par0090" class="elsevierStylePara elsevierViewall">Myelodysplastic syndromes &#40;MDS&#41; are common in the elderly and account for up to 5&#8211;15&#37; of anaemia in this population&#46;<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">35</span></a> It should be suspected when there is a macrocytic anaemia&#44; with normal maturation factors&#44; and other cytopenias&#46;<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">35</span></a> In addition to decreasing survival&#44; MDS have an impact on quality of life&#46; Even forms with better prognosis&#44; such as sideroblastic anaemias&#44; eventually produce important anaemia or thrombopenia&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">The elderly often present molecular lesions similar to those found in patients with established MDS&#46; It is known as <span class="elsevierStyleItalic">clonal haematopoiesis of indeterminate potential</span> &#40;CHIP&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">36</span></a> CHIP&#44; similar to lymphocytosis B and monoclonal gammopathies&#44; also very common in the elderly&#44; it is a stage to follow&#44; since a percentage&#44; which increases with age&#44; will evolve to haematological malignancies &#40;chronic lymphocytic leukaemia&#44; myeloma&#44; MDS&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">37</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Unexplained anaemia in the elderly</span><p id="par0100" class="elsevierStylePara elsevierViewall">It will always be a diagnosis of exclusion&#44; once other causes are ruled out&#46; It is usually a mild to moderate anaemia &#40;Hb<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>g&#47;dl&#41;&#44; hyporegenerative&#44; with low reticulocyte index&#44; inappropriate EPO secretion and normal inflammation markers &#40;IL-6&#44; CRP&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0490"><span class="elsevierStyleSup">38&#8211;43</span></a> Several factors can contribute to UAE&#58; &#40;1&#41; the systemic effects of chronic or subclinical inflammation&#44; including obesity &#40;<span class="elsevierStyleItalic">inflammaging</span>&#41;&#44; through the production of reactive oxygen species and alterations of the medullary microenvironment&#59; &#40;2&#41; decreased production and&#47;or sensitivity to EPO&#44; and reduced availability of micronutrients&#59; &#40;3&#41; the reduction of erythropoietic progenitors &#40;due to the reduction of their self-renewal caused by telomere shortening&#44; DNA damage or epigenetic changes&#41; or their proliferation and maturation capacity&#59; &#40;4&#41; endocrine dysfunctions &#40;decreased androgen and oestrogen&#41;&#59; &#40;5&#41; the medullary toxic effects of some drugs &#40;chemotherapeutic&#44; immunosuppressive&#44; antiviral&#44; anti-folate&#44; etc&#46;&#41; and recreational drugs &#40;alcohol&#41;&#44; or &#40;6&#41; the impact of comorbidity &#40;diabetes&#44; hypertension&#44; sarcopenia&#44; etc&#46;&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0490"><span class="elsevierStyleSup">38&#8211;43</span></a></p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Diagnosis of anaemia in the elderly</span><p id="par0105" class="elsevierStylePara elsevierViewall">Anaemia in the elderly is usually mild-moderate and the onset of symptoms is insidious&#44; so its clinical symptoms are not normally very helpful for diagnosis&#46; Decreased physical activity&#44; fatigue&#44; weakness and dyspnoea can be attributed to the ageing process or the worsening of intercurrent diseases&#59; not so the pallor reflected by low levels of Hb &#40;&#60;9<span class="elsevierStyleHsp" style=""></span>g&#47;dl&#41;&#46; It is often a casual finding in laboratory tests requested for any other cause &#40;e&#46;g&#46;&#44; preoperative laboratory tests&#44; health examinations&#41;&#46;</p><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Medical history and physical examination</span><p id="par0110" class="elsevierStylePara elsevierViewall">They often clarify the aetiology of anaemia&#46; Ask for signs and symptoms associated with bleeding&#44; such as chronic indigestion or dark stools &#40;suggestive of gastrointestinal bleeding&#41;&#44; dark urine &#40;suggestive of haematuria&#41;&#44; or recent surgery&#46; Dietary history is important&#59; strict vegetarian diets increase the risk of vitamin B deficiency<span class="elsevierStyleInf">12</span>&#44; and excessive alcohol consumption that of folate deficiency and bleeding of oesophageal varices and peptic ulcers&#46; Chronic kidney disease and chronic inflammatory diseases are associated with anaemia&#46; Long-term anaemia suggests genetic alterations&#44; such as thalassemia and hereditary spherocytosis&#46; Medications that increase the risk of bleeding &#40;e&#46;g&#46;&#44; anti-inflammatory&#44; antiplatelet&#44; anticoagulant&#41; or alter nutrient absorption &#40;e&#46;g&#46;&#44; antacids&#44; proton pump inhibitors&#44; tetracyclines&#44; metformin&#41; should be checked&#46; The <span class="elsevierStyleItalic">anamnesis</span> &#40;case history-taking&#41; can identify signs of alarm &#40;recent immobility&#44; anorexia&#44; night sweats&#44; weight loss&#44; lymphadenopathy&#44; localized bone pain&#41; suggestive of malignant disease or underlying infection&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Lab tests</span><p id="par0115" class="elsevierStylePara elsevierViewall">Initially&#44; they should include&#58; complete blood count&#44; reticulocytes&#44; creatinine &#40;EGFR&#41;&#44; ferritin&#44; transferrin saturation &#40;TSAT&#41; and C-reactive protein &#40;CRP&#41;&#44; B<span class="elsevierStyleInf">12</span> and folic acid&#46;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">27</span></a> These data will allow us to diagnose the most common anaemias&#58; IDA&#44; CIA&#44; mixed &#40;inflammatory anaemia with iron deficiency&#44; CIA<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>ID&#41;&#44; renal and macrocytic &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; The percentage of hypochromic erythrocytes &#40;&#62;5&#37;&#41;&#44; reticulocyte haemoglobin &#40;CHr<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>28<span class="elsevierStyleHsp" style=""></span>pg&#41;&#44; the soluble transferrin receptor and&#44; above all&#44; the soluble transferrin receptor&#47;log ferritin ratio &#40;&#62;2 in iron deficiency&#41; are useful for differentiating CIA from CIA<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>ID&#44; as well as to predict response to iron treatment&#44; but are not available in all laboratories&#46;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">27</span></a></p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0120" class="elsevierStylePara elsevierViewall">Once IDA has been diagnosed&#44; its origin must be investigated&#46; Digestive pathology &#40;especially blood loss&#41; is often the leading cause in the elderly &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>A&#41;&#46; Invasive tests &#40;gastroscopy&#44; colonoscopy&#44; endoscopic capsule&#41; and non-invasive tests &#40;diagnosis of <span class="elsevierStyleItalic">Helicobacter pylori</span> infection&#44; celiac disease and autoimmune gastritis&#41; should be performed&#46; The determination of occult blood in stools is important&#44; since iron losses due to bleeding higher than 5&#8211;10<span class="elsevierStyleHsp" style=""></span>ml&#47;day exceed the amount of iron the intestine can absorb from a normal diet&#46; In addition&#44; patients with gastroduodenal bleeding up to 100<span class="elsevierStyleHsp" style=""></span>ml&#47;day may present stools with normal appearance&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">If there is no alteration in iron homeostasis&#44; renal failure must be ruled out &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0435"><span class="elsevierStyleSup">27&#44;34</span></a> If the EGFR is &#60;60<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#44; we will consider the presence of renal anaemia &#40;administer EPO&#41;&#59; if it is &#62;60<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> &#40;e&#46;g&#46;&#44; atrophy or gastric resection&#44; bariatric surgery&#44; vegetarian&#44; etc&#46;&#41;&#44; in order to rule out megaloblastic anaemia &#40;vitamin B<span class="elsevierStyleInf">12</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>270<span class="elsevierStyleHsp" style=""></span>pg&#47;ml and folates<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>3<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>B and C&#41;&#46; To calculate the limit values of vitamin B<span class="elsevierStyleInf">12</span> and folates&#44; it is useful to determine the levels of homocysteine &#40;5&#8211;14<span class="elsevierStyleHsp" style=""></span>&#956;mol&#47;l&#41; and methylmalonic acid &#40;70&#8211;270<span class="elsevierStyleHsp" style=""></span>nmol&#47;l&#41;&#46; If both are elevated&#44; vitamin deficiency is confirmed B<span class="elsevierStyleInf">12</span>&#44; although there may be folate deficiency&#46; If homocysteine is high and methylmalonic acid is normal&#44; there is folate deficiency&#46; If the anaemia is associated to a vitamin B deficiency<span class="elsevierStyleInf">12</span>&#44; it is essential to perform a gastroscopy with biopsy to rule out atrophic gastritis&#46;<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">44</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">If maturation factors are normal&#44; we will consider possible haemolysis &#40;haptoglobin&#44; bilirubin&#44; lactate dehydrogenase&#44; erythrocyte morphology&#44; reticulocyte count&#41;&#44; plasma cell dyscrasias &#40;serum and urine protein electrophoresis&#41;&#44; hemoglobinopathies &#40;Hb ID and Hb A2 determinations&#44; Hb electrophoresis&#41; or altered thyroid or hepatic function &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; A macrocytosis associated with other cytopenias suggests MDS or aplastic anaemia &#40;bone marrow examination&#41;&#46; Finally&#44; anaemia will remain as an UAE in a significant number of patients&#46;</p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Treatment of anaemia in the elderly</span><p id="par0135" class="elsevierStylePara elsevierViewall">Healthy elderly do not have to suffer anaemia&#44; rather&#44; they should have levels that are close to the lower limit of normal&#46; Therefore&#44; it is very common for anaemia to be of mixed aetiology&#44; depending on the comorbidities&#44; and its treatment must be etiological &#40;or&#44; failing that&#44; pathophysiological&#41;&#46; Iron and maturation factor supplementation and erythropoiesis stimulating agents &#40;ESA&#41; form the basis of treatment&#44; together with that of the underlying disease&#44; with red blood cell transfusion being reserved for severe cases&#46;</p><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Oral iron</span><p id="par0140" class="elsevierStylePara elsevierViewall">Treatment with iron salts must be initiated in cases of hematin deficiency without anaemia&#44; in isolated IDA and in CIA with iron deficiency due to its efficacy&#44; low cost and acceptable tolerance&#44; although many of the gastrointestinal effects of iron sulfate are dosage independent&#46;<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">45</span></a> In general&#44; it is recommended&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1&#46;</span><p id="par0145" class="elsevierStylePara elsevierViewall">To use low daily &#40;60<span class="elsevierStyleHsp" style=""></span>mg&#41; doses or moderate &#40;100<span class="elsevierStyleHsp" style=""></span>mg&#41; doses every other day&#46; The administration of doses &#8805;60<span class="elsevierStyleHsp" style=""></span>mg increase hepcidin levels for more than 24<span class="elsevierStyleHsp" style=""></span>h&#44; which causes iron absorption to be reduced in the next dose&#46;<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">46</span></a> Doses of 15&#8211;50<span class="elsevierStyleHsp" style=""></span>mg&#47;day have shown efficacy in raising Hb and ferritin in anaemic elderly&#44; with few adverse effects&#46;<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">47</span></a></p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2&#46;</span><p id="par0150" class="elsevierStylePara elsevierViewall">A period of 12<span class="elsevierStyleHsp" style=""></span>h should be observed between administrations in the case of drugs that interfere with the absorption of iron &#40;e&#46;g&#46;&#44; tetracyclines&#44; antacids&#44; proton pump inhibitors&#44; etc&#46;&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">3&#46;</span><p id="par0155" class="elsevierStylePara elsevierViewall">Remember that simultaneous food ingestion reduces its absorption but increases tolerance and therapeutic compliance&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">4&#46;</span><p id="par0160" class="elsevierStylePara elsevierViewall">If there is intolerance to iron salts&#44; switch to an iron compound &#40;iron polymaltose&#44; ferrimanitol ovalbumin&#44; iron casein-succinylate&#44; liposomal iron&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0540"><span class="elsevierStyleSup">48&#44;49</span></a></p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">5&#46;</span><p id="par0165" class="elsevierStylePara elsevierViewall">Re-evaluate after 6&#8211;8 weeks of treatment and change to intravenous &#40;iv&#41; iron if no improvement is observed in Hb&#46;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">27</span></a></p></li></ul></p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Intravenous iron</span><p id="par0170" class="elsevierStylePara elsevierViewall">IV iron administration is a safe and effective alternative for the management of iron deficiency in the elderly&#44; resulting in a better bone marrow response and faster filling of deposits&#46; IV iron would be indicated in cases of contraindication&#44; resistance or intolerance to oral iron&#44; persistent chronic inflammation or bleeding&#44; severe IDA&#44; use of ESA&#44; or preparation for surgery with moderate-to-high bleeding&#46;<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">50</span></a> It would also be indicated in polypharmacy patients in whom pharmacological interactions prevent a correct oral iron absorption&#46; In outpatients&#44; formulations that allow rapid administration &#40;15&#8211;30<span class="elsevierStyleHsp" style=""></span>min&#41; of high doses &#40;e&#46;g&#46;&#44; 1000<span class="elsevierStyleHsp" style=""></span>mg&#41; in a single session &#40;iron carboxymaltose&#44; iron isomaltoside-1000&#41; facilitate the treatment&#46; Lower doses could be used in hospitalized patients &#40;e&#46;g&#46;&#44; sucrose iron&#44; 200<span class="elsevierStyleHsp" style=""></span>mg&#47;session&#41; depending on haematological deficiencies and the estimated length of stay&#46;<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">50</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">Properly indicated and given at appropriate doses&#44; the benefits of IV iron outweigh the risks&#44; the incidence of serious allergic reactions is very low and there are no safety differences among the available preparations&#46;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">51</span></a> However&#44; iv iron is recommended in a healthcare setting with trained personnel and with the means to perform cardiopulmonary resuscitation&#46;<a class="elsevierStyleCrossRefs" href="#bib0555"><span class="elsevierStyleSup">51&#44;52</span></a></p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Vitamin B<span class="elsevierStyleInf">12</span> and folic acid</span><p id="par0180" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Vitamin B</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">12</span></span> is available in the form of hydroxocobalamin and cyanocobalamin&#44; with intramuscular route being the most used &#40;treatment&#58; 1<span class="elsevierStyleHsp" style=""></span>mg&#47;week for 4&#8211;6 weeks&#59; maintenance&#58; 1<span class="elsevierStyleHsp" style=""></span>mg&#47;month&#41;&#46; Use IV route in anticoagulated or haemophilic patients&#44; or oral &#40;500&#8211;1000<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41; in vegetarians&#46; Vitamin B<span class="elsevierStyleInf">12</span> in itself&#44; has no side effects&#44; although cases of anaphylactic shock&#44; angioedema or transient hypertension have been reported after parenteral administration&#44; therefore a test dose is recommended in patients at risk of hypersensitivity&#46;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">53</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Folic acid</span> is primarily administered orally &#40;treatment&#58; 5<span class="elsevierStyleHsp" style=""></span>mg&#47;day for 4 months&#59; maintenance&#58; 5<span class="elsevierStyleHsp" style=""></span>mg&#47;week&#41;&#46; Parenteral administration &#40;folinic acid&#41; is used in patients with poor enteric absorption and to decrease the toxicity of folic acid and 5-fluorouracil antagonists&#46; Folic acid preparations lack side effects&#44; even when given at high doses&#46;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">53</span></a></p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Erythropoiesis stimulating agents</span><p id="par0190" class="elsevierStylePara elsevierViewall">Recent data&#44; while controversial&#44; suggest that ESAs &#40;epoetin&#44; darbepoetin&#44; methoxypolyethylene glycol epoetin&#41; may increase the risk of thrombosis and cancer progression&#44; two adverse events for which the elderly already have an increased risk&#46;<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">54</span></a> Therefore&#44; it seems prudent to associate iron supplements and&#47;or antithrombotic prophylaxis to the administration of ESA and to restrict its use to the approved indications observing the treatment objectives&#58; anaemia in chronic renal failure &#40;target Hb<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>12<span class="elsevierStyleHsp" style=""></span>g&#47;dl&#41;&#44; anaemia in oncology &#40;only for palliative treatment&#59; target Hb<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>12<span class="elsevierStyleHsp" style=""></span>g&#47;dl&#41; and anaemia in elective orthopaedic surgery &#40;baseline Hb 10&#8211;13<span class="elsevierStyleHsp" style=""></span>g&#47;dl&#59; target Hb<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>15<span class="elsevierStyleHsp" style=""></span>g&#47;dl&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">54</span></a> In the UAE&#44; ESAs could also be used &#40;baseline Hb<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>11<span class="elsevierStyleHsp" style=""></span>g&#47;dl&#59; target Hb 11&#8211;12<span class="elsevierStyleHsp" style=""></span>g&#47;dl&#41;&#44; better with IV iron supplements&#44; avoiding sudden variations of Hb and monitoring blood pressure&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">34</span></a></p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Other drugs</span><p id="par0195" class="elsevierStylePara elsevierViewall">Several agents for the treatment of systemic dysfunction&#44; such as the proinflammatory state of ageing&#44; could improve erythropoiesis in the elderly&#46; <span class="elsevierStyleItalic">Nandrolone</span> can enhance the effects of EPO and improve its efficacy in the correction of anaemia&#46; <span class="elsevierStyleItalic">Salsalate</span> reduces low-grade inflammation and improves glycaemic response in obese subjects&#46; <span class="elsevierStyleItalic">Rosuvastatin</span> reduces CRP levels and the incidence of cardiovascular events in adults without hyperlipidaemia&#44; although its anti-inflammatory effects may be accompanied by myalgia and myopathy in 5&#8211;10&#37; of treated patients&#46; <span class="elsevierStyleItalic">Lenalidomide</span> has been used successfully to avoid transfusions in MDS and its administration as an anti-inflammatory may be useful in certain subgroups of anaemic elderly&#46;<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">40</span></a></p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Transfusion of red blood cells</span><p id="par0200" class="elsevierStylePara elsevierViewall">The sole purpose of packed red cells transfusion &#40;PRCT&#41; is to increase the supply of tissue oxygen to alleviate the effects of hypoxia and improve clinical outcome&#46; However&#44; in different medical and surgical settings&#44; an independent association of PRCT with an increased incidence of infections&#44; thromboembolic events&#44; myocardial infarction&#44; in-hospital and at 30 days mortality&#44; prolonged hospital stay&#44; and even increased tumour recurrence&#46;<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">54</span></a></p><p id="par0205" class="elsevierStylePara elsevierViewall">These PRCT disadvantages have led to the recommendation of the use of restrictive transfusion criteria &#40;Hb<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>7&#8211;8<span class="elsevierStyleHsp" style=""></span>g&#47;dl&#41; against more permissive or liberal criteria &#40;Hb<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>9&#8211;10<span class="elsevierStyleHsp" style=""></span>g&#47;dl&#41;&#44; since they reduce the transfusion requirements and the incidence of infections&#44; without increasing morbimortality or hospital stay&#46;<a class="elsevierStyleCrossRefs" href="#bib0575"><span class="elsevierStyleSup">55&#44;56</span></a> However&#44; the studies performed have limitations &#40;e&#46;g&#46;&#44; possible selection bias&#44; lack of a &#8220;routine clinical practice&#8221; group&#44; insufficient sample size or follow-up period to identify low incidence or late onset risks&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">54</span></a> In recent studies&#44; PRCT with &#8220;somewhat more liberal&#8221; criteria would reduce mortality in patients with symptomatic coronary artery disease&#44; cardiac surgery&#44; or non-cardiac major oncologic surgery&#46;<a class="elsevierStyleCrossRefs" href="#bib0585"><span class="elsevierStyleSup">57&#8211;59</span></a> That is&#44; in some groups of patients the use of predefined transfusion thresholds could increase the risk of under-transfusion&#44; compromising their safety&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">Therefore&#44; in elderly medical&#44; critical or surgical patients we should consider that PRCT&#58; &#40;1&#41; is a transitory measure&#59; &#40;2&#41; should be a &#8220;personalized treatment&#8221; based on patient characteristics&#44; Hb concentration&#44; clinical signs and symptoms of anaemia and the degree of monitoring&#59; &#40;3&#41; Hb should be increased or maintained in a &#8220;safety zone&#8221; &#40;usually between 8 and 10<span class="elsevierStyleHsp" style=""></span>g&#47;dl&#41; while anaemia is actively treated&#44; if possible &#40;only one PRBC is an option&#41;&#44; and &#40;4&#41; should be available &#8220;as needed&#8221; &#40;blood bank response time&#41; and be administered by adjusting the infusion to the patient&#39;s cardiovascular characteristics to avoid circulatory overload&#46;<a class="elsevierStyleCrossRefs" href="#bib0570"><span class="elsevierStyleSup">54&#44;55&#44;60</span></a></p></span></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conclusions</span><p id="par0215" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">&#8226;</span><p id="par0220" class="elsevierStylePara elsevierViewall">Anaemia in the elderly is common&#44; increases with age and is an independent risk factor for greater morbidity and mortality in this population&#46;</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">&#8226;</span><p id="par0225" class="elsevierStylePara elsevierViewall">There is no consensus on the level of Hb that defines the presence of anaemia in the elderly&#44; nor on what is the &#8220;healthy level of Hb&#8221; in these individuals&#44; according to their age and comorbidity&#46;</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">&#8226;</span><p id="par0230" class="elsevierStylePara elsevierViewall">The correct classification of anaemia in the elderly can be complicated due to the presence of multiple comorbidities&#44; it requires persistence and yet it is not achieved in a significant proportion of cases &#40;10&#8211;15&#37;&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">&#8226;</span><p id="par0235" class="elsevierStylePara elsevierViewall">When anaemia is of &#8220;unexplained origin&#8221; we have few alternatives with a sound scientific basis for treatment&#46;</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">&#8226;</span><p id="par0240" class="elsevierStylePara elsevierViewall">We do not know if the correction of anaemia eliminates the excess risk of mortality and functional deterioration&#44; although this should not be an obstacle to its treatment&#46;</p></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">&#8226;</span><p id="par0245" class="elsevierStylePara elsevierViewall">We need more studies to know the molecular basis of the pathogenesis of this anaemia and what interventions can improve Hb levels and the physical and functional capacity of these patients&#46;</p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">&#8226;</span><p id="par0250" class="elsevierStylePara elsevierViewall">We should integrate all available information in Clinical Practice Guidelines that facilitate the management of these patients from a multidisciplinary and multimodal perspective&#46;</p></li></ul></p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Conflict of interest</span><p id="par0255" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest&#46;</p></span></span>"
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          "titulo" => "Definition and prevalence of anaemia in the elderly"
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          "titulo" => "Consequences of anaemia in the elderly"
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          "titulo" => "Causes of anaemia in the elderly"
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              "identificador" => "sec0025"
              "titulo" => "Nutrient deficiency"
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              "titulo" => "Chronic inflammatory processes"
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              "titulo" => "Renal failure"
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              "titulo" => "Myelodysplastic syndromes"
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              "titulo" => "Unexplained anaemia in the elderly"
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          "titulo" => "Diagnosis of anaemia in the elderly"
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              "titulo" => "Medical history and physical examination"
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              "titulo" => "Intravenous iron"
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              "titulo" => "Vitamin B and folic acid"
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              "titulo" => "Erythropoiesis stimulating agents"
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              "titulo" => "Other drugs"
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    "fechaAceptado" => "2017-06-17"
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            1 => "Elderly"
            2 => "Nutritional deficiencies"
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            0 => "Anemia"
            1 => "Ancianos"
            2 => "Deficiencias nutricionales"
            3 => "Eritropoyetina"
            4 => "Inflamaci&#243;n"
            5 => "Anemia indeterminada"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Anaemia is common in the elderly and is associated with an increased risk of physical&#44; functional&#44; and cognitive impairment&#44; hospitalization and mortality&#46; Although it is unknown whether anaemia is a causal factor or a subrogated marker of worse health status&#44; its correction can improve the patients&#8217; physical and functional capacity&#46; Detection&#44; classification&#44; and treatment of anaemia should be a priority for the health system&#46; The main causes of anaemia in the elderly are nutritional deficiencies and chronic disease&#44; with or without kidney failure&#44; although some cases are of indeterminate origin&#46; Medical history and physical examination help to clarify its aetiology&#46; A diagnostic algorithm based on data from the lab allows anaemia classification with a therapeutic orientation&#46; Supplements of iron and maturation factors&#44; as well as erythropoiesis-stimulating agents&#44; constitute the mainstay of treatment&#44; along with that of the underlying disease&#44; whereas red blood cell transfusion should be reserved for severe cases&#46;</p></span>"
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      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La anemia es frecuente en los ancianos y se asocia con un mayor riesgo de deterioro f&#237;sico&#44; funcional y cognitivo&#44; hospitalizaci&#243;n y mortalidad&#46; Aunque desconocemos si es un factor causal o un marcador subrogado de un peor estado de salud&#44; su correcci&#243;n puede mejorar la capacidad f&#237;sica y funcional&#46; Su detecci&#243;n&#44; su clasificaci&#243;n y su tratamiento deber&#237;an ser objetivos prioritarios para el sistema de salud&#46; Sus principales causas son las deficiencias nutricionales y las enfermedades cr&#243;nicas&#44; con y sin insuficiencia renal&#44; aunque algunas son de origen desconocido&#46; La historia cl&#237;nica y la exploraci&#243;n f&#237;sica ayudan a aclarar su etiolog&#237;a&#46; Un algoritmo diagn&#243;stico basado en los datos del laboratorio permite su clasificaci&#243;n con orientaci&#243;n terap&#233;utica&#46; Los suplementos de hierro y factores madurativos y los agentes estimuladores de la eritropoyesis constituyen la base del tratamiento&#44; junto con el de la enfermedad de base&#44; reserv&#225;ndose la transfusi&#243;n de hemat&#237;es para los casos graves&#46;</p></span>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; G&#243;mez Ram&#237;rez S&#44; Remacha Sevilla &#193;F&#44; Mu&#241;oz G&#243;mez M&#46; La anemia del anciano&#46; Med Clin &#40;Barc&#41;&#46; 2017&#59;149&#58;496&#8211;503&#46;</p>"
      ]
    ]
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      0 => array:7 [
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        "etiqueta" => "Fig&#46; 1"
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        "figura" => array:1 [
          0 => array:4 [
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        "descripcion" => array:1 [
          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Factors that may contribute to unexplained anaemia in the elderly&#46;</p> <p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">&#42;Decreased production of erythropoietin &#40;EPO&#41; may also be due to kidney disease &#40;diabetes&#44; hypertension&#41; or a decreased <span class="elsevierStyleItalic">hypoxia-inducible factor</span> &#40;HIF&#41;&#46;</p> <p id="spar0030" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Source</span>&#58; adapted from Makipour et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">38</span></a> Ferrucci et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">39</span></a> Merchant and Roy&#44;<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">40</span></a> Baylis et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">41</span></a> Gowanlock et al&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">42</span></a> and Anpalahan et al&#46;<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">43</span></a></p>"
        ]
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      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Fig&#46; 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
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        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Simplified algorithm for the classification of anaemia in the elderly&#46;</p> <p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">IDA&#58; iron deficiency anaemia&#59; UAE&#58; unexplained anaemia in the elderly&#59; CIA&#58; chronic inflammatory anaemia&#59; CIA<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>ID&#58; chronic inflammatory anaemia with iron deficiency&#59; CHr&#58; mean reticulocyte haemoglobin&#59; EPO&#58; erythropoietin&#59; EGFR&#58; estimated glomerular filtrate rate &#40;ml&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#41;&#59; GI&#58; gastrointestinal&#59; MCH&#58; mean corpuscular haemoglobin&#59; CRP&#58; C-reactive protein&#59; MDS&#58; myelodysplastic syndrome&#59; sTfR&#47;log<span class="elsevierStyleHsp" style=""></span>Ft&#58; soluble transferrin receptor ratio&#47;log ferritin concentration&#59; MCV&#58; mean corpuscular volume&#59; ESR&#58; erythrocyte sedimentation rate&#46;</p> <p id="spar0045" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Source</span>&#58; adapted from Mu&#241;oz al&#46;<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">50</span></a></p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
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        "detalles" => array:1 [
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            "identificador" => "at1"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">NSAIDs&#58; non-steroidal anti-inflammatory drugs&#59; AntiH<span class="elsevierStyleInf">2</span>&#58; of histamine H-<span class="elsevierStyleInf">2</span> receptor antagonist&#59; PPI&#44; proton pump inhibitor&#46;</p><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Source</span>&#58; adapted from Evstatiev&#44;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">22</span></a> Ferrucci et al&#46;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">39</span></a> and Pisani et al&#46;<a class="elsevierStyleCrossRef" href="#bib0545"><span class="elsevierStyleSup">49</span></a></p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleBold">A&#46; Iron deficiency</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Increased iron losses</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Peptic ulcer &#40;gastric&#44; duodenal&#44; Cameron&#39;s esophagitis&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Benign or malignant neoplasms&#58; colon&#44; stomach&#44; oesophagus&#44; small intestine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Use of NSAIDs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Inflammatory bowel disease&#58; ulcerative colitis&#44; Crohn&#39;s disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Intestinal parasitosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Vascular disorders&#58; angiodysplasia&#44; hereditary haemorrhagic telangiectasia&#44; gastric antral vascular ectasia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Genitourinary losses&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Decreased absorption of iron</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Celiac disease&#44; Whipple&#39;s syndrome&#44; lymphangiectasis&#44; bacterial overgrowth&#44; gastric atrophy&#44; gastrectomy&#44; intestinal resection or <span class="elsevierStyleItalic">bypass</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Medication&#58; AntiH<span class="elsevierStyleInf">2</span>&#44; PPIs&#44; antacids&#44; etc&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Excess fibre in the diet &#40;especially in vegetarians&#41;&#44; phenolic compounds in tea and coffee&#44; soy &#40;however&#44; absorption of iron increases with intake of fermented foods and proteins&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleVsp" style="height:1.0px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleBold">B&#46; Vitamin B deficiency</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">12</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Inadequate intake&#58; strict vegetarians&#44; alcoholism&#44; malnutrition</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Gastric diseases&#58; pernicious anaemia&#44; gastrectomy&#44; chronic atrophic gastritis</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Diseases of the small intestine&#58; malabsorption syndromes&#44; ileal resection or bypass&#44; Ileal Crohn&#39;s disease&#44; blind loop syndrome</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Pancreatic disease&#58; pancreatic failure</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Drugs&#58; PPI and anti-H</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">2</span></span><span class="elsevierStyleItalic">&#44; metformin&#44; colchicine&#44; neomycin&#44; cholestyramine</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleVsp" style="height:1.0px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleBold">C&#46; Folate deficiency</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Nutritional deficiency&#58; alcoholism&#44; drug addiction&#44; inadequate intake&#44; highly cooked foods</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Malabsorption&#58; inflammatory bowel disease&#44; celiac disease&#44; short bowel syndrome&#44; other small intestinal diseases</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Drugs&#58; methotrexate&#44; trimethoprim&#44; sulfasalazine&#44; phenytoin</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Increased requirements&#58; haemolysis&#44; exfoliative dermatitis</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Main causes of iron deficiency and maturation factors in the elderly&#46;</p>"
        ]
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        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
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          0 => array:3 [
            "identificador" => "at2"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">CRP&#58; C-reactive protein&#59; MCV&#58; mean corpuscular volume&#59; ESR&#58; rate of globular sedimentation&#46;</p><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Source</span>&#58; Adapted from Makipour et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">38</span></a> Ferrucci et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">39</span></a> Merchant and Roy&#44;<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">40</span></a> Baylis et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">41</span></a> Gowanlock et al&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">42</span></a> and Anpalahan et al&#46;<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">43</span></a></p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Parameters&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Common values&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hb&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10&#46;5&#8211;12<span class="elsevierStyleHsp" style=""></span>g&#47;dl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">MCV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">80&#8211;95<span class="elsevierStyleHsp" style=""></span>fL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Platelets and leukocytes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Normal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Morphology&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No signs of dysplasia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Reticulocyte index&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Decreased&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sideremia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Normal &#40;decreased&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total iron transport capacity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Normal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Saturation index&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Normal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Vitamin B<span class="elsevierStyleInf">12</span> and folate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Normal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Thyroid function&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Normal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ESR&#47;CRP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Normal &#40;slightly increased&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Erythropoietin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Not high&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Creatinine clearance&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#62;30<span class="elsevierStyleHsp" style=""></span>ml&#47;min&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hepcidin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Normal &#40;slightly increased&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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Original language: English
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es en pt

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