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array:24 [ "pii" => "S2387020617307040" "issn" => "23870206" "doi" => "10.1016/j.medcle.2017.10.027" "estado" => "S300" "fechaPublicacion" => "2017-12-07" "aid" => "4171" "copyright" => "Elsevier España, S.L.U.. All rights reserved" "copyrightAnyo" => "2017" "documento" => "article" "crossmark" => 1 "subdocumento" => "rev" "cita" => "Med Clin. 2017;149:496-503" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 1 "PDF" => 1 ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S0025775317305110" "issn" => "00257753" "doi" => "10.1016/j.medcli.2017.06.025" "estado" => "S300" "fechaPublicacion" => "2017-12-07" "aid" => "4171" "copyright" => "Elsevier España, S.L.U." "documento" => "article" "crossmark" => 1 "subdocumento" => "rev" "cita" => "Med Clin. 2017;149:496-503" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 125 "formatos" => array:2 [ "HTML" => 93 "PDF" => 32 ] ] "es" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Revisión</span>" "titulo" => "Anemia del anciano" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "496" "paginaFinal" => "503" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Anaemia in the elderly" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figura 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1569 "Ancho" => 2330 "Tamanyo" => 234443 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Algoritmo simplificado para la clasificación de la anemia en el anciano.</p> <p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">AF: anemia ferropénica; AIA: anemia indeterminad del anciano; AIC: anemia inflamatoria crónica; AIC<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>F: anemia inflamatoria con ferropenia; CHr: hemoglobina reticulocitaria media; EPO: eritropoyetina; FGE: filtrado glomerular estimado (ml/min/1,73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>); GI: gastrointestinal; HCM: hemoglobina corpuscular media; PCR: proteína C reactiva; SMD: síndrome mielodisplásico; sTfR/log Ft: cociente receptor soluble de transferrina/log concentración de ferritina; VCM: volumen corpuscular medio; VSG: velocidad de sedimentación globular.</p> <p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Fuente: adaptado de Muñoz el al.<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">50</span></a>.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Susana Gómez Ramírez, Ángel Francisco Remacha Sevilla, Manuel Muñoz Gómez" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Susana" "apellidos" => "Gómez Ramírez" ] 1 => array:2 [ "nombre" => "Ángel Francisco" "apellidos" => "Remacha Sevilla" ] 2 => array:2 [ "nombre" => "Manuel" "apellidos" => "Muñoz Gómez" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2387020617307040" "doi" => "10.1016/j.medcle.2017.10.027" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020617307040?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775317305110?idApp=UINPBA00004N" "url" => "/00257753/0000014900000011/v2_201804270431/S0025775317305110/v2_201804270431/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S2387020617306939" "issn" => "23870206" "doi" => "10.1016/j.medcle.2017.10.016" "estado" => "S300" "fechaPublicacion" => "2017-12-07" "aid" => "4242" "copyright" => "Elsevier España, S.L.U." "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Med Clin. 2017;149:504-5" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Scientific letter</span>" "titulo" => "Atrioventricular block due to papillary fibroelastoma" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "504" "paginaFinal" => "505" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Bloqueo auriculoventricular por fibroelastoma papilar" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Elvis Amao-Ruiz, Ana María Correa-Fernández, Isabel Viqueira-Rodríguez" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Elvis" "apellidos" => "Amao-Ruiz" ] 1 => array:2 [ "nombre" => "Ana María" "apellidos" => "Correa-Fernández" ] 2 => array:2 [ "nombre" => "Isabel" "apellidos" => "Viqueira-Rodríguez" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0025775317306449" "doi" => "10.1016/j.medcli.2017.07.017" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775317306449?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020617306939?idApp=UINPBA00004N" "url" => "/23870206/0000014900000011/v1_201712130718/S2387020617306939/v1_201712130718/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S2387020617307052" "issn" => "23870206" "doi" => "10.1016/j.medcle.2017.10.028" "estado" => "S300" "fechaPublicacion" => "2017-12-07" "aid" => "4177" "copyright" => "Elsevier España, S.L.U." "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Med Clin. 2017;149:493-5" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 1 "PDF" => 1 ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial article</span>" "titulo" => "Importance of rigidity as a cardiovascular risk factor" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "493" "paginaFinal" => "495" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Importancia de la rigidez como factor de riesgo cardiovascular" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Leticia Gómez-Sánchez" "autores" => array:1 [ 0 => array:2 [ "nombre" => "Leticia" "apellidos" => "Gómez-Sánchez" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0025775317305171" "doi" => "10.1016/j.medcli.2017.06.031" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775317305171?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020617307052?idApp=UINPBA00004N" "url" => "/23870206/0000014900000011/v1_201712130718/S2387020617307052/v1_201712130718/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Review</span>" "titulo" => "Anaemia in the elderly" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "496" "paginaFinal" => "503" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Susana Gómez Ramírez, Ángel Francisco Remacha Sevilla, Manuel Muñoz Gómez" "autores" => array:3 [ 0 => array:3 [ "nombre" => "Susana" "apellidos" => "Gómez Ramírez" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 1 => array:3 [ "nombre" => "Ángel Francisco" "apellidos" => "Remacha Sevilla" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 2 => array:4 [ "nombre" => "Manuel" "apellidos" => "Muñoz Gómez" "email" => array:1 [ 0 => "mmunoz@uma.es" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Anemia Working Group España (AWGE), Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Unidad de Gestión Clínica de Medicina Interna, Hospital Clínico Virgen de la Victoria, Málaga, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Hematología, Hospital Sant Pau, Barcelona, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Medicina Transfusional Perioperatoria, Facultad de Medicina, Universidad de Málaga, Málaga, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "La anemia del anciano" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1569 "Ancho" => 2330 "Tamanyo" => 239188 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Simplified algorithm for the classification of anaemia in the elderly.</p> <p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">IDA: iron deficiency anaemia; UAE: unexplained anaemia in the elderly; CIA: chronic inflammatory anaemia; CIA<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>ID: chronic inflammatory anaemia with iron deficiency; CHr: mean reticulocyte haemoglobin; EPO: erythropoietin; EGFR: estimated glomerular filtrate rate (ml/min/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>); GI: gastrointestinal; MCH: mean corpuscular haemoglobin; CRP: C-reactive protein; MDS: myelodysplastic syndrome; sTfR/log<span class="elsevierStyleHsp" style=""></span>Ft: soluble transferrin receptor ratio/log ferritin concentration; MCV: mean corpuscular volume; ESR: erythrocyte sedimentation rate.</p> <p id="spar0045" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Source</span>: adapted from Muñoz al.<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">50</span></a></p>" ] ] ] "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. While you climb, your strength grows weak, but the gaze is freer, 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 (from ≈60 years in 1900 to ≈80 years in 2015) and is estimated to increase further in the future.<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">1</span></a> In the European Union, the proportion of individuals ≥80 years will triple between 2011 and 2060.<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">2</span></a> With age there is an inevitable deterioration of the organic functionality (ageing) that eventually leads to death. Age is also a risk factor for common processes, whether diagnosed or not, such as cardiovascular disease, cancer, diabetes or Alzheimer's disease, which increase the risk of mortality.<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, organic failure and reduction of the functionality have a role in the ageing process. The sum of these factors would give rise to the clinical features in the elderly: frailty, anaemia, malnutrition and poor immune response.<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">1</span></a> Whether anaemia is an independent risk factor for functional impairment, a surrogate marker of a worse health status or simply an additional comorbidity, is something that we still do not know.</p><p id="par0020" class="elsevierStylePara elsevierViewall">A better understanding of the molecular basis of ageing would facilitate the development of interventions that, if applied early, could prevent, delay, alleviate or even reverse some of the diseases related to ageing, thereby gaining years of independent living. That is, we would not only add “years to life”, but also “life to years”.</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 (WHO), the concentration of haemoglobin (Hb) that defines the presence of anaemia in the elderly would be <13<span class="elsevierStyleHsp" style=""></span>g/dl in men and <12<span class="elsevierStyleHsp" style=""></span>g/dl in women.<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">3</span></a> With these definitions, between 1993 and 2005 anaemia affected 24% of the world's elderly (164 million individuals), although with important regional differences.<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">4</span></a> However, there are authors who question its validity in the elderly, in whom an Hb value near the lower limit of normality could be associated with a worse physical and cognitive state.<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> (NHANES III, Phases 1 and 2, 1988–1994; 26,372 individuals), the prevalence of anaemia in individuals ≥65 years of age progressively increased with age (13% in individuals aged 75–84 years, 23% in the 85 years old or more) and was higher among men.<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">6</span></a> In the recent EMPIRE study in Portugal, the prevalence in 1617 individuals >65 years old was also higher in men (22.2%) than in women (19.9%) and increased with age (17.3% in 65–79 years, 31.4% in ≥80 years).<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. In an elderly population of Olmsted County (Minnesota)<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>618, the annual incidence increased with age and was higher in men (90.3 per 1000) than in women (69.1 per 1000).<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">8</span></a> In 465 cases (75%) anaemia was detected during hospital admission, although anaemia was the cause of hospitalization in only 57 cases.<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">8</span></a> In contrast, in the region of Piedmont (Italy)<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>529, the annual incidence of anaemia and mild anaemia were 24.2 and 22.5 per 1000, respectively, with no differences between sexes, but increasing with age (4.9 per 1000 in the 65–69 years group, 72.4 per 1000 in the 80–84 years group).<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 (85,409 elderly), the mean prevalence was 17%, but fell to 6% when anaemia was defined by an Hb<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>11<span class="elsevierStyleHsp" style=""></span>g/dl, indicating that it was mild in most cases. The prevalence was lower among the elderly living in the community (12%) than those living in nursing homes (47%) or that were hospitalized (40%).<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">10</span></a> In the InCHIANTI study, the prevalence of anaemia in the Italian population >65 years of age was 11%, rising to 48–60% in hospitalized individuals.<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">11</span></a> In a series of >300,000 elderly males admitted for non-cardiac surgery in the United States, 43% had a haematocrit <39%, but only <33% in 15% of cases, again indicating that anaemia was mild in most cases.<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">12</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">In Spain, a multicenter study revealed that the prevalence of anaemia in elderly who had undergone surgery<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1687 ranged from 14% in prostate surgery to 61% in colorectal cancer.<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">13</span></a> Among non-operated hospitalized patients (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>796) the mean prevalence was 57% (32% mild, 20% moderate, 5% severe), although there were differences according to the department.<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">14</span></a> Among the outpatient population, a study in the Huesca Sector (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>32,666; 2011–2015) found that the prevalence of anaemia increased with age from 80 years onwards, being higher in men (16 and 12% among the 80–89 years old; 31.6 and 22.4% in >90 years old).<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">15</span></a> The total Spanish population will decrease from 46,507,760 in 2014 to 45,484,908 in 2029, while the population ≥65 years of age will grow from 8,442,887 (18.2%) to 11,275,805 (24.8%) (<a href="http://www.ine.es/prensa/prensa.htm">www.ine.es/prensa/prensa.htm</a>). Extrapolating data from these studies, the number of anaemic elderly will increase from 1100,000 in 2014 to 1500,000 in 2029 (+36%), which will be a significant burden on our health system.</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, decreasing mobility and quality of life.<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">16</span></a> In addition, it increases the risk of fatigue, depression, dementia, hospitalization (due to exacerbations of intercurrent disease, falls) or admission to nursing homes (due to exacerbation of functional deterioration) and mortality (especially if accompanied by other disorders such as heart or kidney failure, high blood pressure or diabetes).<a class="elsevierStyleCrossRefs" href="#bib0385"><span class="elsevierStyleSup">17,18</span></a> In a meta-analysis of 24 studies (949,445 patients), preoperative anaemia (39%) showed an independent association with an increased risk of transfusion, postoperative complications and mortality.<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">19</span></a> For this reason, the detection, classification and treatment of anaemia in the elderly should be a priority objective for the health system.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Hematin deficiencies without anaemia can also have consequences in the elderly. Individuals with hematinic deficiency without anaemia may develop symptoms such as fatigue or decreased exercise tolerance.<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">20</span></a> In congestive heart failure, iron deficiency is associated with decreased physical performance and quality of life and with increased mortality.<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">21</span></a> Iron deficiency can cause secondary thrombocytosis in renal failure, cancer or inflammatory bowel disease, increasing the risk of thromboembolic phenomena.<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">22</span></a> Generally, preclinical or moderate vitamin B deficiency<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">12</span></a> (5–20% of the elderly population) is not accompanied by anaemia but may contribute to cognitive impairment and increased thrombotic risk.<a class="elsevierStyleCrossRefs" href="#bib0415"><span class="elsevierStyleSup">23,24</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; all pathophysiological mechanisms are possible and many of them are simultaneous. In the NAHNES III study, nutritional deficiencies were responsible for 34% of the cases, while chronic diseases, with and without renal failure, accounted for another 33%.<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">7</span></a> In 33% of cases, it was not possible to identify the aetiology (unexplained anaemia in the elderly [UAE]).<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">7</span></a> The high prevalence of UAE (25–45%) in large epidemiological studies on thousands of individuals could simply reflect the use of a limited number of diagnostic tests.<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">17</span></a> When exhaustive studies (necessarily with much fewer cases) are carried out, only 15% of the anaemias are classified as UAE.<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 20–25<span class="elsevierStyleHsp" style=""></span>mg of <span class="elsevierStyleItalic">iron</span> per day, 99% of which comes from Hb recycling of red blood cells in macrophages. Intestinal absorption only contributes 1% and compensates the daily losses. When the absorption decreases or the losses increase (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>A), iron deposits are used, decreasing progressively. This causes a progressive iron deficiency and finally iron deficiency anaemia (IDA), when enough iron is not available to synthesize Hb.<a class="elsevierStyleCrossRefs" href="#bib0430"><span class="elsevierStyleSup">26,27</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. Its absorption depends on the intrinsic factor (synthesized by the gastric parietal cells), and is produced by the “cubam receptor” of the distal ileum. Decreased absorption of vitamin B<span class="elsevierStyleInf">12</span> leads to its deficiency (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>B). The most common cause is the loss of the intrinsic factor secondary to autoimmune atrophic gastritis, which may be found to be anti-intrinsic factor Ab and anti-gastric parietal cell Ab (“pernicious anaemia” or Adisson-Biermer's anaemia). The immune response is directed against the gastric H<span class="elsevierStyleSup">+</span>K<span class="elsevierStyleSup">+</span>-ATPase and is responsible for associated achlorhydria. Autoimmune gastritis can cause malabsorption of iron; with subsequent compromise of vitamin B absorption<span class="elsevierStyleInf">12</span>.<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">28</span></a> Lighter forms of atrophic gastritis, with hypochlorhydria and food-bound vitamin malabsorption (<span class="elsevierStyleItalic">food-cobalamin malabsorption</span>), would lead to preclinical or moderate vitamin B deficiency<span class="elsevierStyleInf">12</span>.<a class="elsevierStyleCrossRefs" href="#bib0415"><span class="elsevierStyleSup">23,24,28</span></a> Less common causes include absence of ileal absorption areas (due to inflammatory enteritis or surgical resection), blind loop syndrome, chronic pancreatitis, and use of certain drugs, such as metformin (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>B).<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, absorption problems or drug interactions (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>C).</p><p id="par0075" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Vitamin D</span> reduces the release of proinflammatory cytokines and hepcidin synthesis, and its deficiency has been associated with chronic inflammatory anaemia (CIA).<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">29</span></a> Individuals with concentrations of 25OHD<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>20<span class="elsevierStyleHsp" style=""></span>ng/ml are more likely to have anemia.<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">30</span></a> In healthy volunteers, oral administration of vitamin<span class="elsevierStyleHsp" style=""></span>D<span class="elsevierStyleInf">2</span> (100,000<span class="elsevierStyleHsp" style=""></span>IU) increased levels of 25OHD (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.01) and reduced hepcidin by 34% during the following 24<span class="elsevierStyleHsp" style=""></span>h (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05), confirming the regulatory role of vitamin D on the hepcidin-ferroportin axis.<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>, since it is involved in the synthesis of the heme group, and <span class="elsevierStyleItalic">vitamin C</span>, which facilitates cellular uptake of transferrin-bound iron.<a class="elsevierStyleCrossRefs" href="#bib0430"><span class="elsevierStyleSup">26,27,32</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 (neoplastic, infectious or inflammatory processes) and is usually moderate and normochromic-normocytic. Some proinflammatory cytokines (tumour necrosis factor-alpha, interleukin-1, interleukin-6 and interferon-gamma) are involved in its development, causing a triple effect: (1) decreased production of erythropoietin (EPO) in response to decreased erythrocyte mass; (2) inhibition of the effect of EPO on erythroid precursors, and (3) poor use of iron by inhibiting its intestinal absorption and reducing its release from macrophages (iron sequestration).<a class="elsevierStyleCrossRefs" href="#bib0430"><span class="elsevierStyleSup">26,27,33</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.<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">7</span></a> Even moderate renal failures (estimated glomerular filtration rate [EGFR]<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>60<span class="elsevierStyleHsp" style=""></span>ml/min/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>) may develop with inadequate synthesis of EPO and anaemia, which in turn may worsen the clinical course of other processes, especially cardiac and respiratory. This anaemia usually responds to relatively low doses of erythropoiesis stimulating agents (ESAs).<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">34</span></a> Some comorbidities and treatments may increase the risk of renal failure (hypertension, diabetes, nonsteroidal anti-inflammatory drugs) and/or reduce the synthesis of EPO (angiotensin-converting enzyme inhibitors).</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Myelodysplastic syndromes</span><p id="par0090" class="elsevierStylePara elsevierViewall">Myelodysplastic syndromes (MDS) are common in the elderly and account for up to 5–15% of anaemia in this population.<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">35</span></a> It should be suspected when there is a macrocytic anaemia, with normal maturation factors, and other cytopenias.<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">35</span></a> In addition to decreasing survival, MDS have an impact on quality of life. Even forms with better prognosis, such as sideroblastic anaemias, eventually produce important anaemia or thrombopenia.</p><p id="par0095" class="elsevierStylePara elsevierViewall">The elderly often present molecular lesions similar to those found in patients with established MDS. It is known as <span class="elsevierStyleItalic">clonal haematopoiesis of indeterminate potential</span> (CHIP).<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">36</span></a> CHIP, similar to lymphocytosis B and monoclonal gammopathies, also very common in the elderly, it is a stage to follow, since a percentage, which increases with age, will evolve to haematological malignancies (chronic lymphocytic leukaemia, myeloma, MDS).<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, once other causes are ruled out. It is usually a mild to moderate anaemia (Hb<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>g/dl), hyporegenerative, with low reticulocyte index, inappropriate EPO secretion and normal inflammation markers (IL-6, CRP) (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<a class="elsevierStyleCrossRefs" href="#bib0490"><span class="elsevierStyleSup">38–43</span></a> Several factors can contribute to UAE: (1) the systemic effects of chronic or subclinical inflammation, including obesity (<span class="elsevierStyleItalic">inflammaging</span>), through the production of reactive oxygen species and alterations of the medullary microenvironment; (2) decreased production and/or sensitivity to EPO, and reduced availability of micronutrients; (3) the reduction of erythropoietic progenitors (due to the reduction of their self-renewal caused by telomere shortening, DNA damage or epigenetic changes) or their proliferation and maturation capacity; (4) endocrine dysfunctions (decreased androgen and oestrogen); (5) the medullary toxic effects of some drugs (chemotherapeutic, immunosuppressive, antiviral, anti-folate, etc.) and recreational drugs (alcohol), or (6) the impact of comorbidity (diabetes, hypertension, sarcopenia, etc.) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).<a class="elsevierStyleCrossRefs" href="#bib0490"><span class="elsevierStyleSup">38–43</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, so its clinical symptoms are not normally very helpful for diagnosis. Decreased physical activity, fatigue, weakness and dyspnoea can be attributed to the ageing process or the worsening of intercurrent diseases; not so the pallor reflected by low levels of Hb (<9<span class="elsevierStyleHsp" style=""></span>g/dl). It is often a casual finding in laboratory tests requested for any other cause (e.g., preoperative laboratory tests, health examinations).</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. Ask for signs and symptoms associated with bleeding, such as chronic indigestion or dark stools (suggestive of gastrointestinal bleeding), dark urine (suggestive of haematuria), or recent surgery. Dietary history is important; strict vegetarian diets increase the risk of vitamin B deficiency<span class="elsevierStyleInf">12</span>, and excessive alcohol consumption that of folate deficiency and bleeding of oesophageal varices and peptic ulcers. Chronic kidney disease and chronic inflammatory diseases are associated with anaemia. Long-term anaemia suggests genetic alterations, such as thalassemia and hereditary spherocytosis. Medications that increase the risk of bleeding (e.g., anti-inflammatory, antiplatelet, anticoagulant) or alter nutrient absorption (e.g., antacids, proton pump inhibitors, tetracyclines, metformin) should be checked. The <span class="elsevierStyleItalic">anamnesis</span> (case history-taking) can identify signs of alarm (recent immobility, anorexia, night sweats, weight loss, lymphadenopathy, localized bone pain) suggestive of malignant disease or underlying infection.</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Lab tests</span><p id="par0115" class="elsevierStylePara elsevierViewall">Initially, they should include: complete blood count, reticulocytes, creatinine (EGFR), ferritin, transferrin saturation (TSAT) and C-reactive protein (CRP), B<span class="elsevierStyleInf">12</span> and folic acid.<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">27</span></a> These data will allow us to diagnose the most common anaemias: IDA, CIA, mixed (inflammatory anaemia with iron deficiency, CIA<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>ID), renal and macrocytic (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). The percentage of hypochromic erythrocytes (>5%), reticulocyte haemoglobin (CHr<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>28<span class="elsevierStyleHsp" style=""></span>pg), the soluble transferrin receptor and, above all, the soluble transferrin receptor/log ferritin ratio (>2 in iron deficiency) are useful for differentiating CIA from CIA<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>ID, as well as to predict response to iron treatment, but are not available in all laboratories.<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, its origin must be investigated. Digestive pathology (especially blood loss) is often the leading cause in the elderly (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>A). Invasive tests (gastroscopy, colonoscopy, endoscopic capsule) and non-invasive tests (diagnosis of <span class="elsevierStyleItalic">Helicobacter pylori</span> infection, celiac disease and autoimmune gastritis) should be performed. The determination of occult blood in stools is important, since iron losses due to bleeding higher than 5–10<span class="elsevierStyleHsp" style=""></span>ml/day exceed the amount of iron the intestine can absorb from a normal diet. In addition, patients with gastroduodenal bleeding up to 100<span class="elsevierStyleHsp" style=""></span>ml/day may present stools with normal appearance.</p><p id="par0125" class="elsevierStylePara elsevierViewall">If there is no alteration in iron homeostasis, renal failure must be ruled out (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).<a class="elsevierStyleCrossRefs" href="#bib0435"><span class="elsevierStyleSup">27,34</span></a> If the EGFR is <60<span class="elsevierStyleHsp" style=""></span>ml/min/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>, we will consider the presence of renal anaemia (administer EPO); if it is >60<span class="elsevierStyleHsp" style=""></span>ml/min/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> (e.g., atrophy or gastric resection, bariatric surgery, vegetarian, etc.), in order to rule out megaloblastic anaemia (vitamin B<span class="elsevierStyleInf">12</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>270<span class="elsevierStyleHsp" style=""></span>pg/ml and folates<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>3<span class="elsevierStyleHsp" style=""></span>ng/ml) (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>B and C). To calculate the limit values of vitamin B<span class="elsevierStyleInf">12</span> and folates, it is useful to determine the levels of homocysteine (5–14<span class="elsevierStyleHsp" style=""></span>μmol/l) and methylmalonic acid (70–270<span class="elsevierStyleHsp" style=""></span>nmol/l). If both are elevated, vitamin deficiency is confirmed B<span class="elsevierStyleInf">12</span>, although there may be folate deficiency. If homocysteine is high and methylmalonic acid is normal, there is folate deficiency. If the anaemia is associated to a vitamin B deficiency<span class="elsevierStyleInf">12</span>, it is essential to perform a gastroscopy with biopsy to rule out atrophic gastritis.<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">44</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">If maturation factors are normal, we will consider possible haemolysis (haptoglobin, bilirubin, lactate dehydrogenase, erythrocyte morphology, reticulocyte count), plasma cell dyscrasias (serum and urine protein electrophoresis), hemoglobinopathies (Hb ID and Hb A2 determinations, Hb electrophoresis) or altered thyroid or hepatic function (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). A macrocytosis associated with other cytopenias suggests MDS or aplastic anaemia (bone marrow examination). Finally, anaemia will remain as an UAE in a significant number of patients.</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, rather, they should have levels that are close to the lower limit of normal. Therefore, it is very common for anaemia to be of mixed aetiology, depending on the comorbidities, and its treatment must be etiological (or, failing that, pathophysiological). Iron and maturation factor supplementation and erythropoiesis stimulating agents (ESA) form the basis of treatment, together with that of the underlying disease, with red blood cell transfusion being reserved for severe cases.</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, in isolated IDA and in CIA with iron deficiency due to its efficacy, low cost and acceptable tolerance, although many of the gastrointestinal effects of iron sulfate are dosage independent.<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">45</span></a> In general, it is recommended:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1.</span><p id="par0145" class="elsevierStylePara elsevierViewall">To use low daily (60<span class="elsevierStyleHsp" style=""></span>mg) doses or moderate (100<span class="elsevierStyleHsp" style=""></span>mg) doses every other day. The administration of doses ≥60<span class="elsevierStyleHsp" style=""></span>mg increase hepcidin levels for more than 24<span class="elsevierStyleHsp" style=""></span>h, which causes iron absorption to be reduced in the next dose.<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">46</span></a> Doses of 15–50<span class="elsevierStyleHsp" style=""></span>mg/day have shown efficacy in raising Hb and ferritin in anaemic elderly, with few adverse effects.<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">47</span></a></p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2.</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 (e.g., tetracyclines, antacids, proton pump inhibitors, etc.).</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">3.</span><p id="par0155" class="elsevierStylePara elsevierViewall">Remember that simultaneous food ingestion reduces its absorption but increases tolerance and therapeutic compliance.</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">4.</span><p id="par0160" class="elsevierStylePara elsevierViewall">If there is intolerance to iron salts, switch to an iron compound (iron polymaltose, ferrimanitol ovalbumin, iron casein-succinylate, liposomal iron).<a class="elsevierStyleCrossRefs" href="#bib0540"><span class="elsevierStyleSup">48,49</span></a></p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">5.</span><p id="par0165" class="elsevierStylePara elsevierViewall">Re-evaluate after 6–8 weeks of treatment and change to intravenous (iv) iron if no improvement is observed in Hb.<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, resulting in a better bone marrow response and faster filling of deposits. IV iron would be indicated in cases of contraindication, resistance or intolerance to oral iron, persistent chronic inflammation or bleeding, severe IDA, use of ESA, or preparation for surgery with moderate-to-high bleeding.<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. In outpatients, formulations that allow rapid administration (15–30<span class="elsevierStyleHsp" style=""></span>min) of high doses (e.g., 1000<span class="elsevierStyleHsp" style=""></span>mg) in a single session (iron carboxymaltose, iron isomaltoside-1000) facilitate the treatment. Lower doses could be used in hospitalized patients (e.g., sucrose iron, 200<span class="elsevierStyleHsp" style=""></span>mg/session) depending on haematological deficiencies and the estimated length of stay.<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, the benefits of IV iron outweigh the risks, the incidence of serious allergic reactions is very low and there are no safety differences among the available preparations.<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">51</span></a> However, iv iron is recommended in a healthcare setting with trained personnel and with the means to perform cardiopulmonary resuscitation.<a class="elsevierStyleCrossRefs" href="#bib0555"><span class="elsevierStyleSup">51,52</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, with intramuscular route being the most used (treatment: 1<span class="elsevierStyleHsp" style=""></span>mg/week for 4–6 weeks; maintenance: 1<span class="elsevierStyleHsp" style=""></span>mg/month). Use IV route in anticoagulated or haemophilic patients, or oral (500–1000<span class="elsevierStyleHsp" style=""></span>mg/day) in vegetarians. Vitamin B<span class="elsevierStyleInf">12</span> in itself, has no side effects, although cases of anaphylactic shock, angioedema or transient hypertension have been reported after parenteral administration, therefore a test dose is recommended in patients at risk of hypersensitivity.<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 (treatment: 5<span class="elsevierStyleHsp" style=""></span>mg/day for 4 months; maintenance: 5<span class="elsevierStyleHsp" style=""></span>mg/week). Parenteral administration (folinic acid) is used in patients with poor enteric absorption and to decrease the toxicity of folic acid and 5-fluorouracil antagonists. Folic acid preparations lack side effects, even when given at high doses.<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, while controversial, suggest that ESAs (epoetin, darbepoetin, methoxypolyethylene glycol epoetin) may increase the risk of thrombosis and cancer progression, two adverse events for which the elderly already have an increased risk.<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">54</span></a> Therefore, it seems prudent to associate iron supplements and/or antithrombotic prophylaxis to the administration of ESA and to restrict its use to the approved indications observing the treatment objectives: anaemia in chronic renal failure (target Hb<span class="elsevierStyleHsp" style=""></span>≤<span class="elsevierStyleHsp" style=""></span>12<span class="elsevierStyleHsp" style=""></span>g/dl), anaemia in oncology (only for palliative treatment; target Hb<span class="elsevierStyleHsp" style=""></span>≤<span class="elsevierStyleHsp" style=""></span>12<span class="elsevierStyleHsp" style=""></span>g/dl) and anaemia in elective orthopaedic surgery (baseline Hb 10–13<span class="elsevierStyleHsp" style=""></span>g/dl; target Hb<span class="elsevierStyleHsp" style=""></span>≤<span class="elsevierStyleHsp" style=""></span>15<span class="elsevierStyleHsp" style=""></span>g/dl).<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">54</span></a> In the UAE, ESAs could also be used (baseline Hb<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>11<span class="elsevierStyleHsp" style=""></span>g/dl; target Hb 11–12<span class="elsevierStyleHsp" style=""></span>g/dl), better with IV iron supplements, avoiding sudden variations of Hb and monitoring blood pressure.<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, such as the proinflammatory state of ageing, could improve erythropoiesis in the elderly. <span class="elsevierStyleItalic">Nandrolone</span> can enhance the effects of EPO and improve its efficacy in the correction of anaemia. <span class="elsevierStyleItalic">Salsalate</span> reduces low-grade inflammation and improves glycaemic response in obese subjects. <span class="elsevierStyleItalic">Rosuvastatin</span> reduces CRP levels and the incidence of cardiovascular events in adults without hyperlipidaemia, although its anti-inflammatory effects may be accompanied by myalgia and myopathy in 5–10% of treated patients. <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.<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 (PRCT) is to increase the supply of tissue oxygen to alleviate the effects of hypoxia and improve clinical outcome. However, in different medical and surgical settings, an independent association of PRCT with an increased incidence of infections, thromboembolic events, myocardial infarction, in-hospital and at 30 days mortality, prolonged hospital stay, and even increased tumour recurrence.<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 (Hb<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>7–8<span class="elsevierStyleHsp" style=""></span>g/dl) against more permissive or liberal criteria (Hb<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>9–10<span class="elsevierStyleHsp" style=""></span>g/dl), since they reduce the transfusion requirements and the incidence of infections, without increasing morbimortality or hospital stay.<a class="elsevierStyleCrossRefs" href="#bib0575"><span class="elsevierStyleSup">55,56</span></a> However, the studies performed have limitations (e.g., possible selection bias, lack of a “routine clinical practice” group, insufficient sample size or follow-up period to identify low incidence or late onset risks).<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">54</span></a> In recent studies, PRCT with “somewhat more liberal” criteria would reduce mortality in patients with symptomatic coronary artery disease, cardiac surgery, or non-cardiac major oncologic surgery.<a class="elsevierStyleCrossRefs" href="#bib0585"><span class="elsevierStyleSup">57–59</span></a> That is, in some groups of patients the use of predefined transfusion thresholds could increase the risk of under-transfusion, compromising their safety.</p><p id="par0210" class="elsevierStylePara elsevierViewall">Therefore, in elderly medical, critical or surgical patients we should consider that PRCT: (1) is a transitory measure; (2) should be a “personalized treatment” based on patient characteristics, Hb concentration, clinical signs and symptoms of anaemia and the degree of monitoring; (3) Hb should be increased or maintained in a “safety zone” (usually between 8 and 10<span class="elsevierStyleHsp" style=""></span>g/dl) while anaemia is actively treated, if possible (only one PRBC is an option), and (4) should be available “as needed” (blood bank response time) and be administered by adjusting the infusion to the patient's cardiovascular characteristics to avoid circulatory overload.<a class="elsevierStyleCrossRefs" href="#bib0570"><span class="elsevierStyleSup">54,55,60</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">•</span><p id="par0220" class="elsevierStylePara elsevierViewall">Anaemia in the elderly is common, increases with age and is an independent risk factor for greater morbidity and mortality in this population.</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">•</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, nor on what is the “healthy level of Hb” in these individuals, according to their age and comorbidity.</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">•</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, it requires persistence and yet it is not achieved in a significant proportion of cases (10–15%).</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">•</span><p id="par0235" class="elsevierStylePara elsevierViewall">When anaemia is of “unexplained origin” we have few alternatives with a sound scientific basis for treatment.</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">•</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, although this should not be an obstacle to its treatment.</p></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">•</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.</p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">•</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.</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.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:13 [ 0 => array:3 [ "identificador" => "xres954873" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec926554" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres954872" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec926553" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Definition and prevalence of anaemia in the elderly" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Consequences of anaemia in the elderly" ] 7 => array:3 [ "identificador" => "sec0020" "titulo" => "Causes of anaemia in the elderly" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "Nutrient deficiency" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "Chronic inflammatory processes" ] 2 => array:2 [ "identificador" => "sec0035" "titulo" => "Renal failure" ] 3 => array:2 [ "identificador" => "sec0040" "titulo" => "Myelodysplastic syndromes" ] 4 => array:2 [ "identificador" => "sec0045" "titulo" => "Unexplained anaemia in the elderly" ] ] ] 8 => array:3 [ "identificador" => "sec0050" "titulo" => "Diagnosis of anaemia in the elderly" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0055" "titulo" => "Medical history and physical examination" ] 1 => array:2 [ "identificador" => "sec0060" "titulo" => "Lab tests" ] ] ] 9 => array:3 [ "identificador" => "sec0065" "titulo" => "Treatment of anaemia in the elderly" "secciones" => array:6 [ 0 => array:2 [ "identificador" => "sec0070" "titulo" => "Oral iron" ] 1 => array:2 [ "identificador" => "sec0075" "titulo" => "Intravenous iron" ] 2 => array:2 [ "identificador" => "sec0080" "titulo" => "Vitamin B and folic acid" ] 3 => array:2 [ "identificador" => "sec0085" "titulo" => "Erythropoiesis stimulating agents" ] 4 => array:2 [ "identificador" => "sec0090" "titulo" => "Other drugs" ] 5 => array:2 [ "identificador" => "sec0095" "titulo" => "Transfusion of red blood cells" ] ] ] 10 => array:2 [ "identificador" => "sec0100" "titulo" => "Conclusions" ] 11 => array:2 [ "identificador" => "sec0105" "titulo" => "Conflict of interest" ] 12 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2017-06-06" "fechaAceptado" => "2017-06-17" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec926554" "palabras" => array:6 [ 0 => "Anaemia" 1 => "Elderly" 2 => "Nutritional deficiencies" 3 => "Erythropoietin" 4 => "Inflammation" 5 => "Indeterminate anaemia" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec926553" "palabras" => array:6 [ 0 => "Anemia" 1 => "Ancianos" 2 => "Deficiencias nutricionales" 3 => "Eritropoyetina" 4 => "Inflamación" 5 => "Anemia indeterminada" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "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, functional, and cognitive impairment, hospitalization and mortality. Although it is unknown whether anaemia is a causal factor or a subrogated marker of worse health status, its correction can improve the patients’ physical and functional capacity. Detection, classification, and treatment of anaemia should be a priority for the health system. The main causes of anaemia in the elderly are nutritional deficiencies and chronic disease, with or without kidney failure, although some cases are of indeterminate origin. Medical history and physical examination help to clarify its aetiology. A diagnostic algorithm based on data from the lab allows anaemia classification with a therapeutic orientation. Supplements of iron and maturation factors, as well as erythropoiesis-stimulating agents, constitute the mainstay of treatment, along with that of the underlying disease, whereas red blood cell transfusion should be reserved for severe cases.</p></span>" ] "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 físico, funcional y cognitivo, hospitalización y mortalidad. Aunque desconocemos si es un factor causal o un marcador subrogado de un peor estado de salud, su corrección puede mejorar la capacidad física y funcional. Su detección, su clasificación y su tratamiento deberían ser objetivos prioritarios para el sistema de salud. Sus principales causas son las deficiencias nutricionales y las enfermedades crónicas, con y sin insuficiencia renal, aunque algunas son de origen desconocido. La historia clínica y la exploración física ayudan a aclarar su etiología. Un algoritmo diagnóstico basado en los datos del laboratorio permite su clasificación con orientación terapéutica. Los suplementos de hierro y factores madurativos y los agentes estimuladores de la eritropoyesis constituyen la base del tratamiento, junto con el de la enfermedad de base, reservándose la transfusión de hematíes para los casos graves.</p></span>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Gómez Ramírez S, Remacha Sevilla ÁF, Muñoz Gómez M. La anemia del anciano. Med Clin (Barc). 2017;149:496–503.</p>" ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1455 "Ancho" => 2531 "Tamanyo" => 216575 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Factors that may contribute to unexplained anaemia in the elderly.</p> <p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">*Decreased production of erythropoietin (EPO) may also be due to kidney disease (diabetes, hypertension) or a decreased <span class="elsevierStyleItalic">hypoxia-inducible factor</span> (HIF).</p> <p id="spar0030" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Source</span>: adapted from Makipour et al.,<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">38</span></a> Ferrucci et al.,<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">39</span></a> Merchant and Roy,<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">40</span></a> Baylis et al.,<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">41</span></a> Gowanlock et al.<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">42</span></a> and Anpalahan et al.<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">43</span></a></p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1569 "Ancho" => 2330 "Tamanyo" => 239188 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Simplified algorithm for the classification of anaemia in the elderly.</p> <p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">IDA: iron deficiency anaemia; UAE: unexplained anaemia in the elderly; CIA: chronic inflammatory anaemia; CIA<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>ID: chronic inflammatory anaemia with iron deficiency; CHr: mean reticulocyte haemoglobin; EPO: erythropoietin; EGFR: estimated glomerular filtrate rate (ml/min/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>); GI: gastrointestinal; MCH: mean corpuscular haemoglobin; CRP: C-reactive protein; MDS: myelodysplastic syndrome; sTfR/log<span class="elsevierStyleHsp" style=""></span>Ft: soluble transferrin receptor ratio/log ferritin concentration; MCV: mean corpuscular volume; ESR: erythrocyte sedimentation rate.</p> <p id="spar0045" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Source</span>: adapted from Muñoz al.<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">50</span></a></p>" ] ] 2 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">NSAIDs: non-steroidal anti-inflammatory drugs; AntiH<span class="elsevierStyleInf">2</span>: of histamine H-<span class="elsevierStyleInf">2</span> receptor antagonist; PPI, proton pump inhibitor.</p><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Source</span>: adapted from Evstatiev,<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">22</span></a> Ferrucci et al.<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">39</span></a> and Pisani et al.<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. Iron deficiency</span> \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> \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 (gastric, duodenal, Cameron's esophagitis) \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: colon, stomach, oesophagus, small intestine \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 \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: ulcerative colitis, Crohn's disease \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 \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: angiodysplasia, hereditary haemorrhagic telangiectasia, gastric antral vascular ectasia \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 \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> \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> \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, Whipple's syndrome, lymphangiectasis, bacterial overgrowth, gastric atrophy, gastrectomy, intestinal resection or <span class="elsevierStyleItalic">bypass</span> \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: AntiH<span class="elsevierStyleInf">2</span>, PPIs, antacids, etc. \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 (especially in vegetarians), phenolic compounds in tea and coffee, soy (however, absorption of iron increases with intake of fermented foods and proteins) \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> \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. Vitamin B deficiency</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">12</span></span> \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: strict vegetarians, alcoholism, malnutrition</span> \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: pernicious anaemia, gastrectomy, chronic atrophic gastritis</span> \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: malabsorption syndromes, ileal resection or bypass, Ileal Crohn's disease, blind loop syndrome</span> \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: pancreatic failure</span> \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: PPI and anti-H</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">2</span></span><span class="elsevierStyleItalic">, metformin, colchicine, neomycin, cholestyramine</span> \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> \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. Folate deficiency</span> \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: alcoholism, drug addiction, inadequate intake, highly cooked foods</span> \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: inflammatory bowel disease, celiac disease, short bowel syndrome, other small intestinal diseases</span> \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: methotrexate, trimethoprim, sulfasalazine, phenytoin</span> \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: haemolysis, exfoliative dermatitis</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1617689.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Main causes of iron deficiency and maturation factors in the elderly.</p>" ] ] 3 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">CRP: C-reactive protein; MCV: mean corpuscular volume; ESR: rate of globular sedimentation.</p><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Source</span>: Adapted from Makipour et al.,<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">38</span></a> Ferrucci et al.,<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">39</span></a> Merchant and Roy,<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">40</span></a> Baylis et al.,<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">41</span></a> Gowanlock et al.<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">42</span></a> and Anpalahan et al.<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 \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 \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10.5–12<span class="elsevierStyleHsp" style=""></span>g/dl \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">80–95<span class="elsevierStyleHsp" style=""></span>fL \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Normal \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 \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 \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Decreased \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Normal (decreased) \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Normal \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Normal \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Normal \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Normal \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/CRP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Normal (slightly increased) \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Not high \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">>30<span class="elsevierStyleHsp" style=""></span>ml/min \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Normal (slightly increased) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1617688.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Characteristics of unexplained anaemia in the elderly.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:60 [ 0 => array:3 [ "identificador" => "bib0305" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Molecular and biological hallmarks of ageing" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "J.R. 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