As the aging population is going to reach unprecedented levels in the 21st century, anemia has become a global problem affecting the quality of life and life expectancy of the elderly and is going to occupy more health resources. Therefore, understanding the general and specific etiology, clinical manifestations, laboratory tests, diagnostic and therapeutic features of anemia in the elderly will help geriatricians to better serve their elderly patients in order to improve their quality of life, prolong their survival, alleviate their pain and rationalize the allocation of medical resources.
The United Nations World Health Organization (WHO) defines anemia in older adults over 65 years of age as hemoglobin less than 130 g/L in men and 120 g/L in women. this criterion is controversial but has been accepted by many hematologists around the world, and China’s Practical Internal Medicine (13th edition, 2009) sets the normal range of hemoglobin in adults as 1 20 to 160 g/L (men) and 1 10 to 150 g/L (female), with no diagnostic criteria for anemia in the elderly. In 2008, Patel reported that in Europe and the United States, the prevalence of anemia in the elderly over 65 years of age was 9.2~23.9% according to the WHO diagnostic criteria for anemia in the elderly. For women, the prevalence was 8.1~24.7%. The third National Health and Nutrition Survey (NHANES
III) showed that the prevalence of anemia in elderly people over 65 years old was 11% for men and 10% for women. After the age of 50, the incidence of anemia increases rapidly and can be as high as about 30% in those over the age of 85. It is estimated that 3 million people over the age of 65 in the United States suffer from anemia. Of those with anemia, 1/3 are malnourished anemia, 1/3 are inflammatory anemia, and the other 1/3 are “unexplained anemia”. There are large racial differences in the prevalence of anemia, with non-Hispanic blacks reported to have three times the prevalence of anemia than non-Hispanic whites in the United States. The Women’s Health and Aging Study I investigated the prevalence of anemia and the relationship between type of anemia and mortality in 688 severely disabled women over the age of 65 years who were enrolled in the study. The results found that the cause of anemia was also “unexplained” in 1/3 of the patients, with significantly higher mortality rates for inflammatory and chronic kidney disease anemias, and a trend toward higher mortality rates for “unexplained anemias,” but not statistically significant.
Common causes of anemia in the elderly]
Anemia in the elderly is more common in men than in women, and it can be one of the clinical manifestations of many diseases, or even the first manifestation of some diseases, which should be given enough attention.
1, lack of hematopoietic materials: including iron, vitamin B12, folic acid and other deficiencies. In addition to dietary factors, gastrointestinal lesions, gastric and jejunostomy, pancreatic lesions, drug application interference, etc., can cause a lack of hematopoietic raw materials and lead to anemia. Iron deficiency anemia is manifested as small cell hypochromic anemia, nutritional megaloblastic anemia is large cell anemia, and sometimes mixed anemia is caused by the lack of iron, vitamin B12 and folic acid.
2. Inflammatory anemia used to be called chronic disease anemia and is commonly seen in chronic infections, rheumatic diseases, pernicious tumors and some other chronic diseases. At the biochemical level, it is characterized by reduced serum iron and total iron binding capacity and increased serum ferritin. Although the etiology of inflammatory anemia has been attributed to shortened erythrocyte lifespan, abnormal erythropoiesis associated with iron metabolism, and progressive resistance to erythropoietin (EPO) by erythroid precursor cells, the role and interrelationship of each of these three mechanisms in the development of anemia is unclear, and perhaps there is some underlying common pathway linking them together.
Aging and aging-related complications are associated with slowly increasing levels of pro-inflammatory cytokines, including TNFα, IL-6, IL-1β, macrophage movement inhibitory factor (MIF), and acute-phase proteins.MIF is secreted by macrophages and T lymphocytes, has broad immune activity, and is significantly increased in the presence of inflammatory disease in the host.MIF acts on macrophages, causing them to release of many pro-inflammatory mediators, such as IL-6, and upstream regulation of TNFα secretion. both MIF and TNFα reduce the formation of red lineage colonies, and MIF may be involved in the pathogenesis of malaria anemia. genes for TNFα, IL-6, IL-1β, and MIF have functional polymorphisms, and the presence of such polymorphisms affects the expression levels of cytokines. TNFα gene polymorphisms are associated with susceptibility to severe malaria and leprosy, and also predict the efficacy of anti-TNF therapy in patients with rheumatoid arthritis. Highly active MIF alleles are associated with inflammatory arthritis, inflammatory bowel disease, and nodular disease. il-6 gene polymorphisms have implications for the phenotype of many benign and pernicious diseases associated with anemia.
Since the discovery of iron-regulator, the understanding of inflammatory anemia has changed. Iron-regulator is a key factor in the regulation of iron metabolism synthesized by the liver. It blocks iron absorption from the intestine and inhibits iron release from macrophages. Unless treated with intravenous iron, iron over-expression in transgenic mice leads to perinatal death due to iron deficiency. In contrast, severe iron overload occurs in iron-regulated knockout mice. Patients diagnosed with inflammatory anemia due to elevated serum ferritin and reduced serum iron and total iron binding have elevated ferroregulin levels. Furthermore, ferromodulin levels are elevated in patients with iron overload due to blood transfusions.
The regulation of ferromodulin synthesis is complex and includes many inflammation-mediated cellular pathways. Ferromodulin is an acute-phase response protein induced by IL-6 and is involved in the regulation of iron metabolism in erythropoiesis in both acute and chronic inflammation. However, there is evidence that anemia may also be mediated by iron-regulated non-dependent pro-inflammatory pathways, such as TNFα. iron-regulated proteins are downregulated in response to hypoxia, and recent studies have shown that high-dose EPO therapy in patients with inflammatory anemia is effective when accompanied by a decrease in iron-regulated proteins.
Leptin, an adipokine associated with inflammation, body fat mass and energy metabolism, induces iron-regulated hormone production via the JAK2/STAT3 signaling pathway, suggesting a potential link between obesity and inflammation and iron metabolism homeostasis. Leptin gene polymorphisms affect its expression, and low leptin levels are associated with a reduced response of erythroid precursor cells to EPO in the elderly.
One study found that the probability of anemia was increased by nearly 60% in vitamin D deficient older adults, with inflammatory anemia being the most common, i.e., the risk of developing inflammatory anemia was significantly higher in vitamin D deficient individuals. The effectiveness and mechanism of vitamin D treatment for inflammatory anemia in the elderly needs to be further explored.
3. Erythropoietin (EPO) deficiency: About 30% of anemia in the elderly is due to absolute or relative deficiency of EPO, and nephrogenic anemia is more common in renal lesions with insufficient EPO production. Anemia is also common in the elderly due to chronic systemic diseases such as rheumatoid arthritis and chronic infections with inadequate EPO production or insensitivity to EPO.
EPO is the main cytokine that affects erythropoiesis and is induced by hypoxic stimulation during the onset of anemia. Reduced hematopoietic stem cell response to EPO is one of the pathogenic mechanisms of senile anemia. The resistance of hematopoietic stem cells to EPO increases progressively with age. The mechanisms may be
(1) Inflammatory factors leading to impairment of normal EPO-dependent cellular pathways.
(2) Decreased responsiveness of the body to anemia and hypoxia due to other age-related complications or decreased renal function.
(3) A combination of these mechanisms. Some patients exhibit EPO deficiency, others, due to adequate expression of iron-regulated elements lead to the development of classic inflammatory anemia. The experience of successful treatment of certain patients with inflammatory anemia with the combined application of EPO and iron supports the above view.
4. Malignant tumors: Among the anemia caused by malignant tumors in the elderly, digestive tract tumors and hematopoietic cell tumors are the most common. Gastrointestinal tumors can lead to anemia, especially iron deficiency anemia, due to long-term chronic blood loss in small amounts or acute hemorrhage. Therefore, for elderly men or postmenopausal women, once they show signs of iron deficiency anemia, it is important to investigate the cause, especially excluding digestive tract tumors. In addition, hematopoietic cell tumors such as leukemia, myelodysplastic syndrome, and multiple myeloma are common in the elderly. The median age of acute granulocytic leukemia is 65 years, and its incidence increases with age, with an annual incidence of 22/100,000 at age 80. The annual incidence of myelodysplastic syndromes is O.5/100,000 at <50 years of age and 49/100,000 at 70-79 years of age. Therefore, these malignant hematological diseases are also often an important cause of anemia in the elderly. Some patients do not have obvious osteolytic lesions, and the change of immunoglobulin amount is not obvious, so it is often misdiagnosed. Therefore, it is necessary to repeatedly perform bone marrow aspiration and immunofixation electrophoresis examination and follow-up for patients with unexplained anemia.
5. Drug-induced anemia: Elderly people often suffer from chronic diseases such as hypertension, coronary heart disease and diabetes, which require long-term medication. The most commonly used ones are such as small doses of aspirin, an anti-platelet aggregation drug, which can cause anemia due to gastrointestinal blood loss in about 2% of patients with long-term application. The elderly are at high risk of malignancy and autoimmune diseases. Anemia caused by cytotoxic drugs and immunosuppressants or immunomodulators (e.g. cyclophosphamide, azathioprine, methotrexate, interferon, etc.) through myelosuppression is predictable, but vigilance and timely management are necessary. Certain drugs such as non-steroidal anti-inflammatory drugs, β-lactam antibiotics, anti-tuberculosis drugs and even certain intravenous herbs for blood circulation may occasionally cause hemolytic anemia through immune mechanism, sometimes life-threatening acute intravascular hemolysis, which requires high vigilance and strict control of medication indications.
6. Unexplained anemia in the elderly: The above are the common causes of anemia in the elderly. However, the etiology of some elderly anemias is not clear, as decreased glomerular filtration rate, decreased sensitivity to EPO, decreased androgens (in both men and women), and decreased proliferative capacity of hematopoietic stem cells can induce anemia in the elderly, which is known as unexplained elderly anemia (UA).
It has been hypothesized that excessive expression of inflammatory factors is an important determinant of “unexplained anemia in the elderly”, inhibiting erythropoiesis through TNFα/IL-1β/MIF on the one hand and impeding iron utilization through IL-6/ferritin on the other. These two mechanisms can lead not only to typical inflammatory anemia, but also to overt anemia where the disturbance of iron metabolism is not obvious.
”Anemia” is a common and very important hematologic problem in the elderly. Although many elderly patients with anemia are diagnosed with nutritional deficiencies, chronic inflammatory conditions, or are thought to be manifestations of other diseases, the etiology of a significant proportion of patients with anemia is unclear. There is evidence that resistance of hematopoietic stem cells to EPO increases with age. In older non-anemic patients, EPO levels are similarly increased, thus contradicting the increased demand for EPO and the decreased ability of the “aged kidney” to produce EPO in the elderly. Furthermore, there is ample evidence that the expression of pro-inflammatory cytokines increases with age, many of which can lead to a decrease in the body’s sensitivity to EPO. The result is that genetic alterations lead to alterations in the expression of pro-inflammatory factors, which in turn lead to the development of anemia in elderly patients, mainly through two mechanisms.
(1) induction of the expression of iron-regulatory factor ferroregulin, a negative regulator of iron.
(2) Direct inhibition of erythropoiesis by cytokines. The effects of inflammatory mediators, EPO insensitivity, and other factors on erythropoiesis are hot issues in current research, and their findings can help to unravel the pathophysiological mechanisms of geriatric anemia and provide assistance in implementing interventions to improve survival and quality of life in the elderly population.
[Clinical characteristics of anemia in the elderly].
The clinical manifestations of anemia in the elderly have some special features compared with the general population. Because of the slow onset of anemia, insidious or atypical symptoms, or masked by other diseases, coupled with poor responsiveness or tolerance, anemia is often misdiagnosed, and even long-term anemia is not corrected in time, which not only delays the disease and misses the timing of treatment, but also promotes the aging process and accelerates the decline of organ functions. Therefore, it is very important to understand the clinical characteristics of anemia in the elderly.
The onset of anemia in the elderly is slow, and some of them have no conscious symptoms, especially in the elderly. Since the symptoms of anemia in the elderly are non-specific, varying and changeable, it is difficult to identify them at once if there are complications. In addition, the presence of atherosclerosis, neurological dysfunction and other factors that reduce the supply of oxygen and tolerance to hypoxia in the elderly, together with the presence of anemia, make brain hypoxia more obvious, which can aggravate the symptoms of the nervous system, such as dizziness, headache, tinnitus, insomnia, dreaminess, memory loss, and even lead to cerebral edema and psychiatric symptoms, such as hallucinations, delusions, depression, easy irritation and In severe cases, it can lead to drowsiness, syncope and coma, etc.
When the elderly are anemic, once they encounter acute and chronic blood loss, rehydration, blood pressure changes, infections, fever, etc., the load on the heart can be increased, and angina pectoris, dyspnea and heart failure can easily occur. At this time, it is easy to misdiagnose as coronary heart disease, pulmonary heart disease, etc., and leave out the anemia and delay the treatment.
Notes for diagnosing senile anemia]
Pay full attention to the collection of clinical data and the questioning of medical history, paying special attention to the contents related to anemia, such as the time frame and triggers of anemia, the presence of chronic blood loss and bleeding disorders, the variety, dosage and time of medication, diet and living and treatment response. For anemia of unknown etiology, it must be dynamically observed and not overshadowed by complications, but analyzed as a whole and comprehensively by summarizing and analyzing the collected information from all aspects and trying to find out the etiology of anemia. The following points should be noted.
1. The diagnosis of senile anemia cannot be based solely on whether the skin mucous membrane is pale or not, because with age, various physiological signs of aging often appear in the elderly, such as skin folds, pale color or pigmented spots, inflammatory congestion and redness of eyelid conjunctiva, and distortion of gum color due to denture, which also affects the accurate determination of oral mucous membrane color.
2.Because of the low function of the central nervous system in the elderly, there are no conscious symptoms of senile anemia, so it is difficult to determine the degree of anemia from the symptoms of anemia, and blood tests are required to determine the degree of anemia.
3. The common symptoms of palpitations, shortness of breath, and inspiratory difficulties in the elderly are not only seen in anemia, but also in cardiopulmonary disorders, so they are sometimes missed due to confusion. Coronary heart disease in the elderly with anemia can easily induce angina pectoris, and severe anemia can appear as cardiac insufficiency.
4. Geriatric anemia is likely to be accompanied by psychoneurological symptoms, such as indifference, confusion, hallucinations, excitement, delusions, insomnia, urinary and fecal incontinence, etc., which are easily misdiagnosed as geriatric psychosis. Most of these symptoms are related to cerebral arteriosclerosis in the elderly.
5. The elderly mostly have some underlying diseases, so it is important to pay attention to the inherent symptoms of anemia that are thus masked. In addition, the bone marrow compensatory capacity of the elderly is low, and once there are unexpected changes, such as bleeding, although the amount of bleeding is not much, the state of acute severe anemia can occur.
6. Elderly people are also prone to malignant blood diseases, such as multiple myeloma, malignant lymphoma, leukemia, etc., or anemia caused by infections, liver or kidney diseases, etc. It is very important to be alert and to identify them.
The prevention and treatment principles of senile anemia]
1.The elderly should have regular and comprehensive physical examination to detect anemia and its causes at an early stage, and once diagnosed, treat carefully and take good care of them according to individual differences.
2. Generally speaking, the treatment of senile anemia is less effective and the cure rate is low because there are many underlying diseases and comorbidities in senile anemia, including those secondary to tumors, infections and chronic diseases. Older people often have poor hematopoietic function, gastrointestinal function, poor absorption of nutrients and poor utilization of hematopoietic substances due to aging, so the prognosis for treatment is poor.
3. Before treatment, we should first clarify the cause, treat the original disease and promptly deal with the complications of anemia. Supplementation of hematopoietic substances, such as iron, vitamin B12, folic acid, vitamin B6, etc., according to different etiologies should be avoided, and blindly mixed abuse of multiple drugs should be avoided.
4. Severe anemia can be treated with blood transfusion, which should take into account the cardiovascular characteristics of the elderly and should be given in small amounts several times to avoid increasing the burden on the heart.
To sum up, as a special group of people, the etiology, occurrence, development and regression of anemia in the elderly have the same and unique features as those in the general population. Knowing the general and special rules of anemia in the elderly helps us to have a deep understanding of the nature of its different types and helps us to formulate treatment plans.