Iron Deficiency As a Common Treatable Cause of Chronic Normocytic Anemia
Authors: Ho Justin CL , Chan Anthony K.C. , Lau Keith K , Chan Howard H.W. 
Published: October 2019

Abstract
Introduction
Normocytic anemia is a common type of anemia, with increasing prevalence in old age. However, diagnosing the etiology of normocytic anemia can be a challenge, as it is a clinical presentation for a vast variety of diseases. Physicians often commence extensive laboratory testing to exclude other differential diagnosis. Although nutritional (iron or vitamin B12/folate) deficiencies are typically associated with microcytic or macrocytic anemia, these deficiencies are readily treatable and iron deficiency is the most common form of anemia worldwide. Therefore, we would like to evaluate the prevalence of iron deficiency in patients initially presented with normocytic anemia.
Methods
This study is a retrospective chart review of patients being referred to an academic hematology clinic from 2003 to 2014 for further evaluation of chronic normocytic anemia without abnormalities in other cell lines. Following initial workup to ensure the absence of 1) mixed microcytic-macrocytic anemia, 2) reticulocytosis, and 3) low erythropoietin level, all patients received a therapeutic trial of iron orally or intravenously. A total of 125 patients (median age: 71 years, range: 24 – 97) had complete records before and after iron therapy for further analysis to determine the changes in hematological parameters and iron indexes.
The patients were categorized by the severity of their anemia, as defined by pretreatment hemoglobin levels below a given age and gender-specific normal range: (1) Hb ≤ 10.0 g/L below normal (n = 54), (2) Hb 10.1 – 20.0 g/L below normal (n = 37), Hb 20.1 – 30.0 g/L below normal (n = 21) and Hb > 30.1 g/L below normal (n = 14). Furthermore, the WHO definition of an increase of Hb ≥ 5.0 g/L was used to signify a response to iron replacement, which might be associated with a subjective improvement in general well-beings.
Results
The overall response rate to iron replacement therapy was 85.6% (Fig. 1), and the anemia was fully corrected in 54.4% of the patients. The average pretreatment ferritin level for these patients was 127 μg/L (median: 85 μg/L, range 3 – 581 μg/L), which would generally not be considered indicative of iron deficiency. Additionally, the response rates among different subgroups were from 83% to 93% (Fig. 1), where the percentage of responders was similar when comparing the mild anemic group (Hb ≤ 10.0 g/L below normal) and the more severe anemic groups. In contrast, although more than 80% of patients with mild normocytic anemia achieved a normal Hb after iron replacement, only 30-40% of patients with moderate to severe anemia (> 10 g/L below normal) experienced a normalization of Hb after iron therapy.
Conclusion
This retrospective case series illustrates that iron deficiency is a common and treatable cause in patients with chronic normocytic anemia. Despite the dogma that patients are unlikely to be iron deficient with a ferritin level ≥ 100 ug/L, more than 80% of patients in this study had an increase in Hb ≥ 5 g/L when iron stores were replenished. The data also suggests that a therapeutic trial of iron replacement should be considered in patients with mild normocytic anemia before extensive workup. However, as the anemia was likely multifactorial in patients with more severe normocytic anemia (with Hb > 10 g/L below the normal range) the benefits of an iron replacement trial should be balanced against the risks of iron overload if patients ultimately require regular blood transfusion for other concomitant hematological disorders.
Fig. 1: Percentage of patients showing an improvement in Hb (≥ 5 g/L) and those having a normalization of Hb after iron therapy Fig. 1:. Percentage of patients showing an improvement in Hb (≥ 5 g/L) and those having a normalization of Hb after iron therapy

Disclosures
No relevant conflicts of interest to declare.