Читать книгу Pathy's Principles and Practice of Geriatric Medicine - Группа авторов - Страница 557

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. In the blood, B12 is bound to a transport protein called transcobalamin and carried into cells to be used for essential reactions in cellular metabolism. In certain cases where gastric pH is high (often medication‐induced or caused by achlorhydria), B12 is not separated from animal proteins, and thus adequate absorption does not occur. Atrophic gastritis, caused by the autoimmune destruction of gastric parietal cells, often leads to inadequate intrinsic factor production and thus vitamin B12 malabsorption with resultant anaemia. One study estimated that 20–50% of vitamin B12 deficiency cases in adults are due to atrophic gastritis.³⁵ It is important to note that a small percentage (1–5%) of ingested vitamin B12 is passively absorbed in the ileum without being bound to intrinsic factor. If not needed for cellular metabolism, vitamin B12 is stored in the liver. Vitamin B12 stores deplete very slowly, and it may take as long at 5–10 years for symptoms to manifest once a deficiency in intake or malabsorption occurs.³⁴

Along with folate deficiency and alcoholism, vitamin B12 deficiency is one of the three most common causes of macrocytosis (defined as blood cells with MCV levels >100 fL) in older adults.³⁶ However, up to 17% of patients do not present with the classic finding of macrocytosis, and up to 28% of B12‐deficient patients have a normal haemoglobin, making the diagnosis challenging at times.³⁷ There is no gold standard diagnostic test for vitamin B12 deficiency. In general, vitamin B12 deficiency anaemia is diagnosed by a low haemoglobin and low vitamin B12 levels on laboratory studies (Figure 22.4). No absolute cut‐off levels defining B12 deficiency exist, and some controversy surrounds what specific level warrants treatment. The WHO suggests that vitamin B12 levels of less than 200 pg/mL be considered deficient, but many research studies use the level of 150 pg/mL to define deficiency. Around these levels, homocysteine and methylmalonic acid (MMA) become elevated and can aide in the diagnostic process, particularly when B12 levels are equivocal (i.e. 200–350 pg/mL).³⁸ In fact, B12 levels of less than 200 pg/mL are associated with the presence of elevated MMA and homocysteine levels with a diagnostic sensitivity of greater than 96%.³⁷ Because MMA is as sensitive as – but more specific than – homocysteine, it is the confirmatory test of choice.³⁷ It should be noted that MMA and homocysteine levels are expensive diagnostic tests and have the best utility when the diagnosis of vitamin B12 deficiency is unclear (i.e. symptomatic patients with low‐normal B12 levels or asymptomatic patients with a high risk of B12 deficiency and low‐normal B12 values). No consensus exists on when additional diagnostic tests should be added.

Vitamin B12 deficiency may lead to non‐specific symptoms such as peripheral neuropathy, gait ataxia, mood changes, weakness, cognitive impairment, vitiligo, and glossitis³⁹; however, symptoms are typically absent. To date, no major medical organization has published guidelines on routine screening for B12 deficiency at the population‐based level. Clinicians should have a high suspicion in at‐risk individuals (i.e. those with history of bowel resection, atrophic gastritis, inflammatory bowel disease, or specialized diets and metformin or acid‐suppressant users) and consider screening on an annual basis. It should be noted that falsely normal B12 levels can occur in those with hepatic or renal disease or myeloproliferative disorders. Falsely low B12 values may be seen in those with folate deficiency or multiple myeloma.⁴⁰

Fortunately, vitamin B12 deficiency anaemia is readily treatable. The goals of treatment are to alleviate any symptoms, if present, and replenish the vitamin B12 stores in the liver. Treatment options include intramuscular (IM) B12 or oral B12. The typical IM dose is 1000 mcg weekly for severe deficiency and then monthly for maintenance treatment. About 10–15% of each injection is absorbed, so stores are replenished quickly. However, in most cases, oral supplemental B12 is as effective as IM supplementation and is less costly. Oral B12 can be absorbed even in the presence of inadequate acid secretion because it does not have to be broken apart from animal protein to be bound to intrinsic factor.⁴¹ Higher oral doses (2000 mcg daily) can be used indefinitely to treat B12 deficiency from pernicious anaemia/atrophic gastritis because of the small amount of passive free absorption of B12 not bound to intrinsic factor that occurs.⁴² No evidence‐based guidelines dictate specific dose efficacy or treatment duration. In general, haemoglobin and vitamin B12 levels should be checked again around three months after treatment initiation to ensure treatment success. In those with pernicious anaemia or history of gastric or bowel resection, the treatment will be needed indefinitely because absorption with these conditions will likely remain deficient.

Figure 22.4 Diagnostic laboratory values for vitamin B12 deficiency anaemia.

In summary, vitamin B12 deficiency anaemia results from inadequate vitamin B12 intake or malabsorption. There is no gold standard diagnostic test. The diagnosis relies on the presence of anaemia (RBCs may or may not be macrocytic) and a low B12 level. Serum MMA and homocysteine levels can be added to increase diagnostic sensitivity but are not required. Treatment can occur via oral or IM supplementation, but in general, oral supplementation is easier and less costly to administer, and likely as effective in most cases if given at high enough doses. Haemoglobin and B12 levels can be rechecked in three months after initiation of supplementation to validate treatment response.