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.
Vitamin B12 deficiency anaemia
Vitamin B12 deficiency anaemia is much less common than IDA in older adults but can be associated with significant morbidity and should be evaluated. The prevalence of vitamin B12 deficiency (also known as cobalamin deficiency) increases with age and ranges between 5–40% depending on the cut‐off level used.29‐31 One Canadian study of 412 nursing home residents found the overall prevalence to be 13.8% on nursing home admission and a new yearly incidence rate of 4% one‐year post‐admission.32
Vitamin B12 deficiency anaemia can result from either inadequate intake or impaired absorption. Similar to iron deficiency, inadequate intake can occur in those who follow specialized or vegetarian diets. Unlike iron, however, vitamin B12 is strictly found in animal products, including red meat, eggs, and dairy, making vegetarians or vegans particularly susceptible to deficiencies. Medications that decrease the acidity of the stomach, such as proton pump inhibitors and histamine‐2 blockers, can impair B12 absorption. Metformin, a commonly used medication for treatment of diabetes mellitus, is also associated with B12 deficiency, and long‐term users should be screened for deficiency.33 Other causes of impaired absorption include a history of intestinal or gastric resection, intestinal bacterial overgrowth, inflammatory bowel disease, and atrophic gastritis.
Vitamin B12 is a water‐soluble vitamin and plays an important role in cellular metabolism. It is required for DNA synthesis, mitochondrial function, and red blood cell production.34 It also converts folate to its biologically active form and, when deficient, can cause a folate deficiency. In the stomach, vitamin B12 is cleaved from animal proteins by stomach acid and then bound to R‐protein. The R‐protein/B12 complex travels to the duodenum, where it is cleaved by pancreatic enzymes; the resultant B12 molecule is then bound to intrinsic factor, which is secreted by gastric parietal cells. The B12/intrinsic factor complex continues to the terminal ileum, where it is absorbed into the blood circulation.