**5. Types of anemia**

As per National Health and Nutrition Examination Survey III anemia has been classified into four categories as per underlying cause such as anemia from nutritional deficiency, anemia due to renal diseases, anemia of chronic disease and unexplained anemia, in the absence of other specific causes.

Anemia of chronic disease (ACD) is found to be the most common cause of anemia. The prevalence of ACD varies from 33.1–77% in elderly patients (**Table 1**) [1, 37, 48].

The cause of ACD in hospitalized elderly patients is mostly the consequence of added chronic underlying diseases and also is an indicator of several reactive and clonal conditions.3 Many underlying diseases, like H pylori, renal impairment, congestive heart failure, myelodysplastic syndrome (MDS) is seen associated with ACD in elderly [19, 42, 51]. Although concentrations of serum ferritin, white blood counts (WBC) and C-reactive protein (CRP) levels in ACD patients remains high in ACD but high Hepcidin (H) level occurring due to inflammation facilitates development of ACD in elderly patients. Wang WJ et al. have emphasized that best threshold value for the diagnosis of ACD is 130.05 μg/L with the sensitivity of 72% and the specificity of 96% [51–53]. An analysis done by López-Sierra Metal also favored use of serum Transferrin Receptor (sTfR) to check out the state of erythropoiesis in patients with chronic disease [54].


**Table 1.**

*Prevalence of anemia of chronic disease in geriatric age group.*

Nutritional deficiency anemia is an important clinical problem with prevalence varying from 4% to 22.5% in older patients associated with caloric and protein restriction, iron, vitamin B12, folic deficiency [19, 37, 48, 55]. Protein and energy malnutrition cause an increase in the production of cytokine, stimulation of inflammationand anemia. Due to decreased macrophages activity and ineffective erythropoiesis, reduced red cell mass is seen. In addition, increased cytokines and hepcidin serum levels also seen associated with obesity and underweight [56]. Anemia patients with protein and energy malnutrition more frequently suffered from hypoalbunemia [43]. Absolute IDA is well-defined as anemia with absence of total body iron. To diagnose IDA although serum ferritin is the most often used parameter, but with older age and in the presence of inflammatory diseases concentration of serum ferritin increases and losses its significancy.10Iron deficiency anemia (IDA) contributes approximately 13–15% of total anemia of geriatric age group, mainly associated with underlying diseases.Evidence has been supported by improvement of IDAfrom iron rich diet in geriatric patients [1, 37, 48, 55, 57–59]. New insights into iron homeostasis lead to new diagnostic assays such as serum baseline hepcidin levels could be a useful tool to identify ID in anemic elderly patients. Wang WJ et al. have highlighted thatthe best threshold in diagnosis of IDA was 93.31 μg/L with the sensitivity of 88% and the specificity of 89% [53, 54, 60, 61]. In addition serum transferrin receptor and reticulocyte hemoglobin equivalent is also an emerging investigation to diagnose the disease [54].

Anemia due to CKD fall under the category of decreased RBC production and prevalence varies from 13.2–27% of geriatric anemia [19, 49]. In a smaller number of cases, no clear-cut causes of anemia are identified and when a clear etiopathogenesis is ruled-out the anemia is defined as unexplained anemia (UA) term unexplained anemia. Although the reasons are still under-explored but common pathophysiological mechanisms seems to be associated with an age-related inflammatory process [62, 63]. These patients with unidentified causes are referred to as unexplained anemia or idiopathic cytopenia of unknown significance. The erythropoietin genesis in the kidney becomes suboptimal due to age related affects or changes. This aspect is still underestimated and unexplored while dealing with unexplained anemia. The prevalence of UA varies from 5.8% to 43.7% of the cases (**Table 2**). Many researchers have worked on UA, Price EA and fellows have observed mildly increased inflammatory markers and low erythropoietin levels in patients with this entity. Roy CN and associates have observed that testosterone treatment in case of men 65 years or older with UA and low testosterone levels significantly increased the hemoglobin levels. In testosterone trials, testosterone treatment increased Hb levels in both men who had anemia of a known cause and in men with UA [3, 37, 61, 64–66]. However, similar survival was observed in geriatric patients with UA compared with non-anemic subjects but mortality risks was increased in patients with deficiency anemia compared with non-anemic subjects [49]. The erythropoietin levels seen


**Table 2.** *Prevalence of unexplained anemia.*

inappropriately low in UA indicating that decreased erythropoietin production plays an important role in the pathogenesis of anemia of unknown etiology [50]. On further cytogenetic analysis of UA, one researcher found myelodysplastic syndrome in 4% of the total anemic patients [67]. Whereas in others, present somatic mutations were not found fit as per diagnostic criteria for MDS and condition was termed as clonal cytopenia of undetermined significance [68].
