What causes a low reticulocyte (reticulocyte count) level?

From the Guidelines

A low reticulocyte count is typically caused by decreased red blood cell production in the bone marrow, which can result from various conditions, including iron deficiency anemia, vitamin B12 or folate deficiency, chronic kidney disease, bone marrow disorders, certain medications, radiation therapy, and severe infections or inflammation. To address a low reticulocyte count, the underlying cause must be identified and treated. This may involve:

• Iron supplementation (e.g., ferrous sulfate 325 mg orally 1-3 times daily) for iron deficiency, as indicated by low iron and total iron binding capacity (TIBC) resulting in transferrin saturation less than 15% and ferritin less than 30 ng/mL 1
• Vitamin B12 injections (e.g., 1000 mcg intramuscularly weekly for 4 weeks, then monthly) for B12 deficiency, diagnosed by low vitamin B12 levels 1
• Folic acid supplementation (e.g., 1 mg orally daily) for folate deficiency, also diagnosed by low folate levels 1
• Treating underlying kidney disease or infections, which can cause a low reticulocyte count due to insufficient erythropoietin production or inflammation 1
• Adjusting medications if they are the cause, such as chemotherapy drugs or other medications that can suppress bone marrow function A complete blood count (CBC) and additional tests like iron studies, vitamin B12 levels, and kidney function tests may be necessary to determine the exact cause. In some cases, a bone marrow biopsy may be required to evaluate for bone marrow disorders. Reticulocytes are immature red blood cells, and their count reflects the bone marrow's ability to produce new red blood cells. A low count indicates decreased production, which can lead to anemia if not addressed promptly.

The reticulocyte index (RI) is a useful measure to evaluate the bone marrow's response to anemia, with a low RI indicating decreased RBC production 1. The most common reason for inadequate reticulocyte response in patients with chronic kidney disease (CKD) is likely to be either insufficient erythropoietin production or inflammation 1. Therefore, it is essential to evaluate iron sufficiency and assess for gastrointestinal bleeding in patients with CKD and iron deficiency 1.

In clinical practice, a low reticulocyte count should prompt a thorough evaluation of the underlying cause, and treatment should be tailored to address the specific condition. By identifying and treating the underlying cause, it is possible to improve the reticulocyte count and prevent or manage anemia, ultimately improving patient outcomes in terms of morbidity, mortality, and quality of life.

From the FDA Drug Label

If severe anemia and low reticulocyte count develop during treatment with PROCRIT, withhold PROCRIT and evaluate patients for neutralizing antibodies to erythropoietin For lack or loss of hemoglobin response to PROCRIT, initiate a search for causative factors (e.g., iron deficiency, infection, inflammation, bleeding).

A low reticulocyte count level can be caused by several factors, including:

• Neutralizing antibodies to erythropoietin 2
• Iron deficiency 2
• Infection 2
• Inflammation 2
• Bleeding 2

From the Research

Causes of Low Reticulocyte Count

• A low reticulocyte count can be caused by various factors, including:
  • Pure red cell aplasia (PRCA), a rare condition characterized by the near-complete absence of erythroid precursor cells in the bone marrow 3
  • Iron deficiency anemia, which can lead to a decrease in reticulocyte production 4, 5, 6
  • Vitamin B12 deficiency anemia, which can also affect reticulocyte production 5
  • Mixed anemia, which can be caused by a combination of iron and vitamin B12 deficiencies 5
  • Bone marrow disorders or diseases that affect erythropoiesis, such as anemia of chronic disease 4, 7
• A low reticulocyte count can also be seen in cases of:
  • Acquired immunodeficiency syndrome (AIDS) 3
  • Parvovirus infection 3
  • Certain medications or toxins that suppress bone marrow function 3

Diagnostic Approaches

• The diagnosis of a low reticulocyte count typically involves a combination of:
  • Complete blood count (CBC) with red cell indices 4, 5, 7
  • Reticulocyte count and indices, such as reticulocyte hemoglobin content and mean reticulocyte volume 4, 5, 6
  • Iron studies and vitamin B12 levels to evaluate for deficiencies 4, 5, 6
  • Bone marrow examination in some cases to evaluate for underlying disorders 3, 7