Читать книгу Pathy's Principles and Practice of Geriatric Medicine - Группа авторов - Страница 556

Iron deficiency is the most common nutritional disorder worldwide and is therefore the most common type of anaemia across all age groups worldwide. Iron deficiency anaemia (IDA) is also one of the most treatable forms of anaemia and results from one of the following: inadequate iron intake, decreased iron absorption, increased iron demand, or accelerated iron loss.¹⁴ Inadequate iron intake can occur in those with malnutrition or who follow specialized diets. Older adults may be at higher risk of malnutrition due to higher frequencies of social isolation leading to poor appetite and less food consumption, financial constraints limiting the buying of high‐quality food, lack of transportation to obtain food, and inability to prepare meals due to illness or immobility.¹⁵ Decreased iron absorption is also more common in older adults and can result from medications such as proton pump inhibitors, which decrease the acidity of the stomach and prevent conversion of iron to its absorbable form.¹⁶ Decreased iron absorption is also more likely in those who have had stomach or bowel resection and those with inflammatory bowel diseases. Achlorhydria, caused by the autoimmune destruction of gastric parietal cells (i.e. atrophic gastritis or pernicious anaemia) or bacterial overgrowth, frequently results in disrupted iron absorption. Increased iron demand can occur in states of rapid red blood cell turnover such as in chronic kidney disease, where many factors lead to earlier red blood cell destruction, or haemolytic anaemias, where there is autoimmune‐driven destruction of red blood cells. Accelerated iron loss frequently occurs in acute and chronic bleeding states.

Figure 22.2 Most prevalent types of anaemia in older adults.

Figure 22.3 Diagnostic laboratory values for iron deficiency anaemia, anaemia of chronic disease, and anaemia of chronic kidney disease.

Iron is found in many varieties of food sources, with red meat containing the highest amounts, and is necessary for the synthesis of oxygen transport proteins found in haemoglobin and oxidation reductions necessary for cellular metabolism. It is consumed in the ferric formulation (Fe³⁺) and converted by the acidity of the stomach to the ferrous formulation (Fe²⁺). It is absorbed primarily in the duodenum, with lesser amounts absorbed in the jejunum through the iron transporter ferroportin, and is then bound to the protein transferrin, which acts as its carrier in the blood.¹⁷ If not needed in muscle or for immediate use in red blood cell production, iron is stored bound to the protein ferritin in the liver. Because we consume only a small amount of iron each day (1–2 mg/day), iron homeostasis depends highly on recycling iron from senescent red blood cells. Hepcidin, a peptide produced by the liver, is a key regulator in the homeostasis process and regulates iron absorption from enterocytes and also the release of bound iron from ferritin.¹⁸

Laboratory studies are used to diagnose IDA because symptoms are often non‐specific or can be absent. When present, symptoms may result from the lack of iron itself or the resultant anaemia and may include tachycardia, pallor, fatigue, pica, cold intolerance, and dyspnoea. In general, low haemoglobin, low serum iron, high total iron‐binding capacity (TIBC), increased transferrin with low transferrin saturation, and reduced ferritin level are necessary to make the diagnosis of IDA (Figure 22.3). IDA is typically thought of as a microcytic anaemia, but up to 40% of patients will have normocytic RBCs – particularly early in the disease process.¹⁴ The diagnosis of IDA should not be considered in patients with macrocytosis and mean corpuscular volumes (MCV) greater than 95 fL (sensitivity of 98%).¹⁹ Ferritin levels of less than 30 ng/mL have a high sensitivity and specificity (92 and 98%, respectively) for the diagnosis of IDA.²⁰ It can be challenging to distinguish between IDA and other types of anaemia because ferritin is an acute‐phase reactant and becomes intrinsically elevated in inflammatory states, and thus it may not be reflective of actual iron stores. When the ferritin level is equivocal or between 30 and 100 ng/mL, this may represent IDA, mixed anaemia, or anaemia of chronic disease. However, it is important to note that ferritin levels greater than 100 ng/mL generally exclude IDA, even with a co‐existing inflammatory state.²¹ The TIBC level, which represents the sum of all iron‐binding sites on transferrin, can be used to calculate the transferrin saturation and is typically high in IDA. The transferrin saturation represents the percent of transferrin iron‐binding sites filled with iron and is less than 20% in IDA. Another useful laboratory test to distinguish IDA from other anaemias is the soluble transferrin receptor level, which is an indirect measure of iron status and unaffected by inflammation.²⁰ The soluble transferrin receptor level is increased in IDA, but cost and availability are prohibitive in clinical settings. The traditional gold standard diagnostic test for IDA is a bone marrow iron stain. This is rarely used because of the invasiveness and expense of a bone marrow biopsy.

Once IDA is identified, the underlying aetiology should be established so appropriate treatments can be implemented. For deficiencies from malabsorptive states, inadequate iron intake, or increased iron demand, supplementation is the mainstay of treatment. The aim of treatment is to supply enough iron to normalize haemoglobin concentrations and replenish iron stores. Two treatment options exist: oral (PO) and intravenous (IV) supplementation. In general, PO supplementation is less readily absorbed than the IV formation and will be less effective in the presence of conditions that affect oral absorption. IV iron replenishes iron stores quicker and in fewer doses and may be the better treatment choice when iron and ferritin levels are extremely low or the anaemia is severe. However, IV iron supplementation is more expensive and requires expertise for administration (typically done in a hospital or infusion centre), but has less gastrointestinal side effects than PO supplementation. Several PO formulations are available, including ferrous gluconate, ferrous sulfate, and ferrous fumarate, and differ from one another by the amount of elemental iron contained. It should be noted that once‐daily dosing of any formulation is sufficient because enterocyte receptor saturation occurs, which prevents absorption of further doses.²² Studies have been done in older patients, confirming that low‐dose iron therapy (i.e. once‐daily dosing) is effective, is more tolerable, and leads to less side effects than more frequent dosing.²³ Reticulocyte counts will start to increase approximately 4–7 days after the initiation of treatment, and haemoglobin levels should rise within 14 days. There are no established evidence‐based guidelines for exact treatment duration, but in most cases PO supplementation should be continued for three to six months after initiation. A ferritin level should be checked to ensure repletion of iron stores before discontinuation of supplementation. If the IDA isn’t correcting with PO treatment, a more comprehensive evaluation should be undertaken to assess for malabsorption or ongoing bleeding. It is important to note that tea can reduce iron absorption from supplements or food sources by 90%, whereas ascorbic acid (vitamin C) can increase the bioavailability of iron and improve absorption.^24,25

In cases of accelerated iron loss (i.e. acute or chronic bleeding), invasive diagnostic tests such as ultrasounds, esophagogastroduodenoscopy (EGD), or colonoscopy may be indicated, although no clear guidelines exist on which procedure should be performed first.²⁶ In premenopausal women, menstruation is a common cause for IDA. In both older men and postmenopausal women, gastrointestinal bleeding sources (i.e. gastritis, bleeding ulcers, arteriovenous malformations) are common and must be further investigated. Specifically, gastrointestinal malignancies (i.e. colon or gastric cancer) are of concern and occur in up to 10% of those older than 65 with new diagnosis of IDA.²⁷ IDA can also be seen in up to 25–50% of those who have had bariatric weight‐loss surgery because bowel resection, especially of the duodenum, interferes with iron absorption.²⁸

In summary, IDA is caused from inadequate iron intake, decreased iron absorption, increased iron demand, or accelerated iron loss. It is typically diagnosed by laboratory studies that show a low haemoglobin, low serum iron, high TIBC, low transferrin saturation, and reduced ferritin levels. A ferritin level of less than 30 ng/mL is diagnostic of IDA, whereas a ferritin level greater than 100 ng/mL generally excludes the diagnosis of IDA. Iron deficiency is treated with IV or PO iron supplementation depending on severity of anaemia, absorption profile, cost, and tolerability of side effects. Oral supplementation should be given only once daily due to receptor saturation and lack of absorption with more frequent dosing. For those who do not respond to supplementation, further investigation must be undertaken to rule out chronic bleeding sources.