Date Published: October 3, 2012
Publisher: Hindawi Publishing Corporation
Author(s): Antonio Macciò, Clelia Madeddu.
Anemia of any degree is recognized as a significant independent contributor to morbidity, mortality, and frailty in elderly patients. Among the broad types of anemia in the elderly a peculiar role seems to be played by the anemia associated with chronic inflammation, which remains the most complex form of anemia to treat. The origin of this nonspecific inflammation in the elderly has not yet been clarified. It seems more plausible that the oxidative stress that accompanies ageing is the real cause of chronic inflammation of the elderly and that the same oxidative stress is actually a major cause of this anemia. The erythropoietic agents have the potential to play a therapeutic role in this patient population. Despite some promising results, rHuEPO does not have a specific indication for the treatment of anemia in the elderly. Moreover, concerns about their side effects have spurred the search for alternatives. Considering the etiopathogenetic mechanisms of anemia of inflammation in the elderly population, an integrated nutritional/dietetic approach with nutraceuticals that can manipulate oxidative stress and related inflammation may prevent the onset of this anemia and its negative impact on patients’ performance and quality of life.
The number of elderly individuals is expected to reach unprecedented levels in the twenty-first century. Anemia represents an emerging global health problem that negatively impacts quality of life in a significant proportion of the elderly population and requires an ever-greater allocation of healthcare resources.
To date, it is generally accepted that the causes of anemia in the elderly can be divided into three broad groups as follows: (a) nutrient-deficiency anemia, which is most often iron-deficiency anemia; (b) anemia of chronic disease, perhaps better termed anemia of chronic inflammation; (c) unexplained anemia . In the NHANES III study, 34% of all cases of anemia in elderly patients were caused by folate, vitamin B12, or iron deficiency, either alone or in combination (nutrient-deficiency anemia); 20% were due to chronic diseases; in 34% the cause remained unexplained (including myelodysplasia) . NHANES III classified iron-deficiency anemia with other nutritional anemias, a classification that might be correct in the developing third world, but in North America and Western Europe, iron deficiency is more often caused by blood loss and the cause must be sought and dealt with . In fact, while some cases of iron deficiency results from diet, blood loss through gastrointestinal lesions is the primary cause in older adults .
In healthy humans, the concentration of iron in plasma and extracellular fluid is maintained at a relatively narrow range of 10–30 μM, ensuring that adequate iron is available for essential cellular functions without incurring iron toxicity. The plasma iron concentration is controlled by the hepatic peptide hormone hepcidin, which regulates the major iron flows into plasma: dietary iron absorption in the duodenum (1-2 mg/d), iron recycling from senescent erythrocytes (20 mg/d), and the recovery of iron from storage in hepatocytes and macrophages (a few milligrams per day depending on iron needs). Transferrin-bound iron exits the plasma compartment destined predominantly for the bone marrow erythrocyte precursors, where it is incorporated into heme and hemoglobin. Smaller amounts of iron are taken up by other cells, where they are incorporated into myoglobin, redox enzymes, and other iron-containing proteins .
Although the role of chronic inflammation in the etiopathogenesis of some anemias in elderly subjects has been clearly determined, a safe and appropriate treatment protocol has not yet been described. Treatment considerations for elderly patients with anemia include correcting the underlying condition, transfusing red blood cells, antagonizing of etiopathogenetic mechanisms (inducing this particular anemia), and administering of recombinant human erythropoietin (rHuEPO) (Table 1). The only experiences with a good chance of success were those made with recombinant human erythropoietin.
With the continued elderly population growth, anemia will likely continue to be a significant economic burden on society. The challenge for treating and laboratory-based physicians is to understand the underlying causes and contributing factors that result in anemia in the elderly so that the potential value of emerging and innovative pharmacologic management can be considered. Including CRP and hepcidin in the diagnostic algorithm for anemia may better discriminate between classic iron-deficiency anemia (low hepcidin levels) and iron-deficiency anemia in the context of anaemia of inflammation or chronic disease (elevated hepcidin levels) .