Anaemia in Elderly - How to Approach

 Dr. Tarun Verma, Head Department of Hemato-Oncology & Bone Marrow Transplant, HCG (Health Care Global) Enterprises HCG is the India’s largest provider of cancer care with state-of-the-art facilities for diagnosis and treatments for PET CT, PET MRI, 3T MRI, IGRT, IMRT, and Cyber Knife robotic radiosurgery and many more.

Anaemia in elderly persons is a significant public health concern, yet frequently under diagnosed & unrecognized. Among the many reasons are that elderly persons are often not symptomatic due to lack of physical activity, compensatory mechanisms, neglect by self and others, especially for old-age home residents, as well as the presence of multiple comorbidities which may mask the signs & symptoms of anaemia.

Many studies have shown anaemia as an independent predictor of both morbidity & mortality in the elderly, worsening in severity with increasing age of the patient. One large study found a prevalence of anaemia in men & women over 65 years of age of 11 percent and 10 percent, respectively, increasing up to 30 percent and 18 percent, respectively, for subjects over 85 years of age. Further the three-year mortality(from any cause)among anaemic & non-anaemic patients, in another study, was estimated to be significantly different at 36 percent and 28 percent, respectively.

In addition to mortality, anaemia has been linked to quality of life issues such as impaired physical performance, falls in the elderly, dementia, impaired comprehension and ability for self-care, hospitalizations and symptomatic coronary artery disease. Also, since weight loss and anaemia often run hand-in-hand and complement each other, patients often suffer both and are prone to infections, malnutrition and immobilization.

In all, it is a major public health problem, which requires community-based screening, management and monitoring beginning with the primary care physician. There is, thus, a need to sensitize & educate healthcare providers, especially those involved in the care of the elderly, as the list of differential diagnosis is not extensive. Diagnosis & treatment are, therefore, not very complicated and often very gratifying.

Causes of Anaemia
Three broad etiological categories comprise roughly about 30 percent each of anaemia in the elderly.
1. Deficiency of iron, folic acid and/or vitamin B 12
2. Anaemia of Chronic Disease(ACD)- this includes auto-immune diseases, chronic inflammation, infections, chronic kidney disease, and malignancy
3. Unexplained Anaemia of Elderly(UAE)

Nutrional Anaemia
Iron deficiency accounts for nearly half of so-called nutritional anaemia. It is diagnosed in the presence of suggestive red blood cell indices along with consistent biochemical parameters: serum iron <60 µg/dl in men,
<50µg/dl in women; transferrin saturation <16 percent, ferritin <30 ng/ml. A majority of cases are diet related, especially in Indians, however, GI blood loss can account for a significant number of cases and should always be investigated. The problem is that the lab parameters are not always reliable in the elderly, such as ferritin, which tends to rise with age. In addition, a host of factors may lead to tissue sequestration of iron, leading to functional iron deficiency even in the presence of sustainable bone marrow iron deposits. Thus, it is usually worth while to give a trial of oral iron before ruling-out iron deficiency.

"There is, thus, a need to sensitize & educate healthcare providers, especially those involved in the care of the elderly, as the list of differential diagnosis is not extensive"

Folic acid deficiency has become uncommon in some countries, as a result of fortification of cereals with folate. However, it is still a common entity in some risk groups as patient on dialysis, GI surgery patients and alcoholics. B 12 deficiency is common in some elderly people, such a pure vegetarians, and partial gastrectomy patients. Folate & B 12 deficiency can be reliably diagnosed in the presence of macrocytosis, ovalocytosis and folate <3.0 ng/ml and B 12 < pg/ml, respectively.

Anaemia of Chronic Disease
This category encompasses a broad range of entities ranging from auto-immune disease, to renal failure and malignancy. Anaemia is usually normocytic, normochromic but may be microcytic with low reticulocyte count. ACD is usually diagnosed in the presence of low circulating iron in the presence of adequate tissue reserves suggestive of tissue sequestration, mediated by cytokines and hormones such as hepcidin.

A typical profile would be serum iron 50 µg/dl, TIBC <250 µg/dl, ferritin >100 ng/ml, transferrin saturation 25-50 percent. The basic pathology revolves around sequestration of iron in reticulo-endothelial cells thereby resulting in iron restricted erythropoiesis. A number of cytokines, such as TNF α, IFN γ and IL 1 are implicated in upregulation of DMT1, hepcidin as well as reduced synthesis and biological activity of erythropoietin(EPO).

Unexplained Anaemia of Elderly
This complex yet common entity remains a diagnosis of exclusion, and comprises mild-moderate, normocytic, hypoproliferative anaemia with low reticulocyte count and inappropriately low EPO levels in the elderly. Some of the postulated causes include reduction in the progenitor cell mass, blunting of EPO effect, testosterone deficiency. It has been described in at least one third of all large series of anaemia in the elderly, one study reporting finding UAE in 43.7 percent cases. Myelodysplastic Syndrome and functional iron deficiency need to be excluded.

When approaching a case of anaemia, in the elderly, defined as H <13 g/dl in males and <12 g/dl in females, the following investigations are advisable, to begin with, followed by specific diagnostic testing, as indicated
• CBC, differential counts
• Peripheral smear, retic count
• Renal function tests
• Liver function tests, including albumen
• Iron studies – iron, TIBC, ferritin
• Serum B 12 and serum/ RBC folate
• Serum EPO
• Serum TSH
• C reactive protein, ESR, fibrinogen
• Hb electrophoresis – to exclude haemoglobinopathy
• Serum LDH, haptoglobin – for haemolytic anaemia
• Bone marrow studies in case of pancytopenia, unexplained macrocytosis
• Stool – occult blood ± endoscopy

Treatment is dictated by the underlying cause. As mentioned earlier, functional iron deficiency may exist despite demonstrable tissue iron stores. Therefore, unless a definite diagnosis is reached, a short trial of oral iron, as well as B 12 & folic acid may be given. In case of ACD, EPO is the most appropriate therapy with dose being tailored to patient response. An inflammatory etiology is suggested by leukocytosis, thrombocytosis, or acute phase reactants such as CRP, fibrinogen. For UAE, EPO and/or androgens are therapeutic alternatives. In all cases, the treatment modality should be weighed against the clinical urgency, such as the severity of anaemia and the comorbidities. Thus, moderate-severe anaemia in symptomatic coronary artery disease may warrant immediate correction with packed cell transfusions. On the other hand, a planned routine surgery may be deferred, pending correction of Hb with iron/ EPO thus avoiding transfusion.