From the Guidelines
A low ferritin level with normal hemoglobin and reticulocyte count suggests iron deficiency without anemia, also called iron depletion, and I recommend oral iron supplementation to replenish iron stores and prevent potential complications. The goal ferritin level is 50 ng/mL, regardless of sex at birth, as stated in the expert consensus guidelines 1. I recommend oral iron supplementation, typically ferrous sulfate 325 mg once or twice daily, taken on an empty stomach with vitamin C to enhance absorption. Alternative formulations include ferrous gluconate or ferrous fumarate if sulfate causes intolerable gastrointestinal side effects.
Some key points to consider in the management of iron deficiency without anemia include:
- Investigating the cause of iron deficiency, which may include blood loss (menstruation, gastrointestinal bleeding), poor dietary intake, or malabsorption 1
- Dietary changes to include iron-rich foods (red meat, beans, leafy greens) should complement supplementation
- Monitoring laboratory parameters, including ferritin and transferrin saturation, 4-8 weeks after initiation of therapy to assess response to treatment 1
- Considering the use of soluble transferrin receptor (sTfR) or reticulocyte hemoglobin content (CHr) to evaluate iron status, especially in patients with inflammatory conditions or those who are not responding to treatment as expected 1
It is essential to continue supplementation for 3-6 months to replenish iron stores, with follow-up ferritin testing after 2-3 months to assess the response to treatment. While hemoglobin remains normal, low iron stores can cause fatigue, reduced exercise tolerance, and cognitive symptoms even before anemia develops. The normal reticulocyte count indicates that the bone marrow is not currently increasing red blood cell production in response to anemia, but iron stores are depleted.
From the Research
Reticulocyte Count and Low Ferritin with Normal Hemoglobin
- A low reticulocyte count can indicate iron deficiency anemia, even with normal hemoglobin levels 2, 3, 4, 5, 6
- Reticulocyte hemoglobin content (CHr) is a useful marker for diagnosing iron deficiency and monitoring iron therapy 2, 3, 5, 6
- CHr has a moderate sensitivity and specificity for diagnosing iron deficiency and is less affected by inflammation than serum iron, transferrin saturation, and ferritin 2
- A study found that a CHr cutoff value of 25 pg had a sensitivity of 94% and specificity of 80% for predicting iron deficiency in a pediatric population 5
- Another study found that a CHr cutoff value of 22.4 pg had a sensitivity of 98.88% and specificity of 84.21% for predicting iron deficiency anemia 6
- Reticulocyte hemoglobin content is a reliable test for investigating iron deficiency and can improve the detection of iron-deficient adults 3
- CHr can quickly track the success of therapy and help identify the main factors inhibiting erythropoiesis, regardless of the cause of anemia 4
Diagnostic Value of Reticulocyte Hemoglobin Content
- Reticulocyte hemoglobin content has a high diagnostic value for iron deficiency, with an area under the curve (AUC) of 0.851 in one study 3
- CHr is a better predictor of bone marrow iron stores than serum ferritin, with a significant positive correlation between the two 6
- The AUC for reticulocyte hemoglobin content was found to be 0.894, indicating high diagnostic accuracy for iron deficiency anemia 6
Clinical Applications
- Reticulocyte hemoglobin content can be used to screen for iron deficiency, diagnose iron deficiency anemia, and monitor iron therapy 2, 3, 4, 5, 6
- CHr can help identify patients with functional iron deficiency anemia, which can occur in acute or chronic diseases or inflammation 2
- Reticulocyte hemoglobin content is a valuable tool for patient blood management, allowing for early detection and treatment of iron deficiency and anemia 4