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These circumstances include iron-refractory iron-deficiency anaemia and overt intolerance to different oral iron preparations. But it has also been used in other indications, especially associated with erythropoietin (EPO) treatment in patients with chronic renal failure (CRF) to avoid the first cause of lack of response to EPO, such as functional iron deficiency (situation in which the iron requirements needed will surpass the deposits present at that moment). This term implies an iron status with ferritin <100<span class="elsevierStyleHsp" style=""></span>mg/dl and a saturation of the transferrin<20%<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> for some authors, especially if there is no CRF, and in cases of CRF, a ferritin<500<span class="elsevierStyleHsp" style=""></span>mg/dl and saturation of transferrin <30%.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> To a lesser extent it had been used for the treatment of chronic disease anaemias in the context of inflammatory diseases, especially rheumatoid arthritis or inflammatory bowel disease, although its use has experienced a remarkable increase in the latter.</p><p id="par0010" class="elsevierStylePara elsevierViewall">IV Fe was first used in 1947 (saccharide iron); subsequently, high-molecular weight dextran iron was used in 1954, but the high number of serious adverse reactions (11.3<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">6</span>) made its use very limited until the arrival of low molecular weight dextran iron in 1991; in 1999 iron gluconate was used and it is in the year 2000, with iron sucrose, when IV Fe becomes widely used.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3,4</span></a> More recently, since 2009, new iron presentations with the same safety profile as iron sucrose have been marketed, with the advantage of allowing the administration of more iron in less time (carboxymaltose, ferumoxytol and isomaltose).</p><p id="par0015" class="elsevierStylePara elsevierViewall">The use of IV Fe had drawbacks (the occurrence of important adverse reactions and its slow administration being among the more important), which have been clearly improved in recent years with the new formulations. The functionality and safety of the molecule has also been improved, making it possible to administer more iron and in a shorter time, greatly improving access to these treatments. This has meant that the number of situations in which it can be used has significantly increased, as well as its global use.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Regarding the preparations available in our country, no comparative studies have been conducted between the formulations that allow higher doses, although economic studies have been carried out (especially with carboxymaltose) in emergency units, cardiology or anaesthesiology, where, besides safety, they demonstrate an economic saving.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">5,6</span></a> The Ganzoni formula has been used when calculating the amount of iron to be replaced, which is based on body weight, haemoglobin (Hb) levels with respect to the desired values and the amount of iron element, but this formula should only be used in cases of pure iron deficiency, not in mixed anaemia, where part of the anaemia is due to other reasons, since it can lead to a replacement excess with the subsequent overload. The use of IV Fe requires experience, especially with high doses.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Regarding clinical use, its scope of use has been increasing, since it was initially used for cases of oral intolerance to iron, and had a great role in the concomitant treatment with EPO in patients with renal failure to improve its response and in turn decrease the EPO doses required.</p><p id="par0030" class="elsevierStylePara elsevierViewall">The current indications include<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a>: oral route failure (lack of adherence, side effects); malabsorption (celiac disease, gastritis, bariatric surgery, gastrectomy, iron-refractory iron-deficiency anaemia (IRIDA)); the need for a rapid recovery from iron deficiency; CRF (along with EPO treatment); inflammatory bowel disease (active disease); pregnancy (severe iron deficiency in the second and third trimesters); heart failure (systolic heart failure, Fe <45%) and as a possible alternative to transfusion when this is not accepted.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Currently, it is used regularly for the treatment of many iron deficiency disorders (not only those refractory or intolerant to oral iron), as the availability of formulations that allow the administration of more significant iron doses has, in certain cases, managed to avoid transfusions by allowing selected patients with severe anaemia (for example, non-cardiac patients, good tolerance to anaemia) to recover 1–2<span class="elsevierStyleHsp" style=""></span>g of Hb in one week. In the case of oral iron intolerance, at least 3 different products should be tried, including ferrous salts and ferric salts. Within refractory anaemia we would have those patients with some type of malabsorption such as chronic atrophic gastritis, <span class="elsevierStyleItalic">Helicobacter pylori</span> infection, gastric resections, bypass surgery or celiac disease, among the most frequent, as well as those patients with inflammatory bowel disease, patients in whom treatment with IV Fe has contributed, along with the rest of the therapeutic advances of these diseases, to the clear improvement of their anaemias, which range between pure iron-deficiency and those of a mixed blockade/deficiency pattern with a significant inflammatory component and, therefore, high levels of hepcidin, which inhibit the intestinal absorption of iron, making them extremely resistant to treatment. In this sense, we also have the use of IV Fe in the context of functional iron deficiency in patients with CRF treated with EPO or other similar situations. As presentations with greater amounts of iron became available in haemorrhage units, these treatments have become vitally important, as they have been replacing transfusions whenever possible. It should be taken into account that the response to severe anaemia after IV Fe treatment is not as immediate as with a transfusion, even when high doses are used; so, patients should be selected according to whether they can wait a few days for the response. Therefore, in emergency situations with very severe anaemia or with comorbidities, especially cardiac and pulmonary, waiting for the effect of iron treatment may not be an option, and therefore the patient will have to be transfused.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Iron doses have been consolidated in preoperative periods. These have clearly improved iron-deficiency anaemia without the need for transfusion and have greatly reduced the delay before the intervention (mainly colorectal surgeries), allowing corrections in about 15–21 days with intravenous treatment.</p><p id="par0045" class="elsevierStylePara elsevierViewall">In nephrology patients, they continue to be used to the same extent, but above all they have improved in safety of administration, since there has been a distinctive before and after, with a clear decrease in serious adverse reactions. In functional iron deficiency, cases of poor response have been greatly reduced due to a better interpretation of iron metabolism and the advent of new parameters in haematology analysers, which allow a better iron status evaluation in reticulocytes, such as the content of reticulocyte Hb and the percentage of hypochromic red blood cells. These parameters are used in nephrology guidelines such as <span class="elsevierStyleItalic">National Kidney Foundation-Kidney Disease Outcomes Quality Initiative</span>, for the follow-up and response to treatment with human recombinant EPO in patients with CRF on dialysis,<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">8,9</span></a> and allow to better adjust the EPO doses maintaining good responses and optimizing costs related to its use.</p><p id="par0050" class="elsevierStylePara elsevierViewall">A particularly interesting case has been the use of IV Fe together with EPO in the treatment of patients with heart failure, known as cardiorenal anaemia or cardiorenal syndrome, which was first described around the year 2000 and has been increasing with a pathophysiology quite similar to that of renal failure. This syndrome shares characteristics with inflammatory or chronic disease anaemia, the only difference being that the lack of EPO is not due to a secretory defect, but mainly due to an inhibition of its release. Initially, it was used in the final stages of heart failure (class III and IV of the NYHA), but now it is used from class II. It was observed that these patients did not improve despite the optimal treatment of heart disease, with a progressive anaemia that could, in turn, worsen heart failure, accompanied by increased morbidity and mortality. Anaemia is a <span class="elsevierStyleItalic">per se</span> complication risk factor of the underlying disease. Through several meta-analyses it was found that they presented higher morbidity but did not seem to increase mortality. The joint use of IV Fe together with EPO reduces the dose of EPO to be used, with less cost and less risk. It also improves the response by decreasing the development of functional iron deficiency.</p><p id="par0055" class="elsevierStylePara elsevierViewall">IV Fe has also been used in the context of inflammatory processes (for example, rheumatoid arthritis) with the presence of inflammatory or chronic disease anaemia, although it may have been used to a lesser extent, not being a clear indication at present. In these cases, there seems to be no difference in response time between the use of parenteral iron and the use of EPO, reason why the use of IV Fe alone is more common than the combination of both.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Cancer is the entity with more disparities, since there are groups that confer a carcinogenic possibility and, therefore, contraindicate its use in patients with active cancer, except in case of clear iron deficiency. In many occasions, since the pathophysiology of anaemia in cancer patients is multifactorial, transfusions are usually administered; this is partly justified due to the use of chemotherapy associated with bone marrow toxicity.</p><p id="par0065" class="elsevierStylePara elsevierViewall">In the field of obstetrics, it is increasingly common to use IV Fe during pregnancy, not in the first trimester, in which it is contraindicated, but later, thus avoiding the undesirable effects of oral iron (gastric discomfort, constipation), so annoying, especially in this group of patients. Nevertheless, it should be reserved for moderate-severe and postpartum anemias.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Current potential indications include: iron deficiency or iron deficiency anaemia in the elderly (comorbidities, adherence); perioperative anaemia (<span class="elsevierStyleItalic">Patient Blood Management</span> strategies to avoid transfusions) and iron deficiency in cancer.</p><p id="par0075" class="elsevierStylePara elsevierViewall">Therefore, the improvement in safety profiles, shorter time of administration and higher doses have led to an increase in its use, especially in the currently approved indications, leaving new potential indications open for consideration. All this has led to the development of guidelines and treatment protocols by the different specialties accustomed to its use. However, it is still important to assess the iron status carefully (laboratory criteria used for the definition of iron deficiency or functional iron deficiency and therapeutic objectives in terms of iron deficiency), so as to select the patients to be treated, to use the oral route whenever possible (IV Fe when necessary) and administer the appropriate dose without causing iron overload, which is one of the problems to be avoided, and, in this way, the best results will be achieved without hardly any adverse effects.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Beneitez Pastor D. Uso del hierro intravenoso en la clínica actual.. 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Journal Information
Vol. 150. Issue 5.
Pages 188-190 (March 2018)
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Vol. 150. Issue 5.
Pages 188-190 (March 2018)
Editorial article
Use of intravenous iron in the current clinical practice
Uso del hierro intravenoso en la clínica actual
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David Beneitez Pastor
Unidad de Anemias, Eritropatología y Patología Congénita Serie Roja, Servicio de Hematología Clínica, Hospital Universitari Vall d’Hebron, Barcelona, Spain
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