What is the diagnosis for anemia with normal iron studies (ferritin and transferrin saturation)?

From the Guidelines

Anemia with normal iron studies should be investigated for causes other than iron deficiency, with a focus on anemia of chronic disease, vitamin B12 or folate deficiency, hemolytic anemia, or bone marrow disorders, as these conditions can significantly impact morbidity, mortality, and quality of life. The most common causes of anemia with normal iron studies include anemia of chronic disease, thalassemia, vitamin B12 or folate deficiency, hemolytic anemia, or bone marrow disorders. Initial management should include a complete blood count with reticulocyte count, peripheral blood smear, and specific testing based on clinical suspicion, as recommended by the European Consensus on the diagnosis and management of iron deficiency and anaemia in inflammatory bowel diseases 1.

Key Considerations

• Anemia of chronic disease involves treating the underlying condition, which can be complex and require a multidisciplinary approach, as seen in patients with chronic kidney disease (CKD) where anemia is a frequent complication 2.
• Vitamin B12 or folate deficiency can be treated with supplementation, with cyanocobalamin 1000 mcg daily orally for 1-2 weeks, then weekly for a month, then monthly for life for B12 deficiency, and folic acid 1-5 mg daily until resolution for folate deficiency.
• Hemolytic anemia management depends on the cause, which may require steroids or immunosuppressants for autoimmune hemolysis, and bone marrow disorders may need hematology referral.
• The underlying pathophysiology varies by cause, with B12/folate deficiencies impairing DNA synthesis and red cell maturation, thalassemia involving abnormal hemoglobin production, and chronic disease anemia resulting from inflammatory cytokines disrupting iron utilization despite adequate stores.

Diagnostic Approach

• A complete blood count with MCV, reticulocytes, serum ferritin, transferrin saturation, and CRP should be performed as the minimum workup, as recommended by the European Consensus 1.
• More extensive workup may include vitamin B12, folic acid, haptoglobin, a differential white blood cell count, and bone marrow smear, depending on the clinical suspicion and initial test results.
• A wide size range of the red cells (high RDW) can help in situations where microcytosis and macrocytosis co-exist, as RDW is an indicator of iron deficiency 1.

Treatment and Monitoring

• Treatment should be tailored to the underlying cause of anemia, with a focus on improving morbidity, mortality, and quality of life.
• Patients should be monitored with repeat CBC at appropriate intervals based on the specific diagnosis and treatment, with adjustments made as needed to optimize outcomes.

From the FDA Drug Label

2.1 Important Dosing Information Evaluation of Iron Stores and Nutritional Factors Evaluate the iron status in all patients before and during treatment. Administer supplemental iron therapy when serum ferritin is less than 100 mcg/L or when serum transferrin saturation is less than 20%. The majority of patients with CKD will require supplemental iron during the course of ESA therapy.

The FDA drug label does not directly answer the question of anemia with normal iron studies. However, it mentions that iron status should be evaluated in all patients before and during treatment, and supplemental iron therapy should be administered when serum ferritin is less than 100 mcg/L or when serum transferrin saturation is less than 20%.

• The label does not provide information on the treatment of anemia with normal iron studies.
• It emphasizes the importance of evaluating and managing iron stores and nutritional factors in patients with anemia.
• The use of epoetin alfa is indicated for the treatment of anemia due to chronic kidney disease, zidovudine in patients with HIV infection, chemotherapy in patients with cancer, and reduction of allogeneic red blood cell transfusions in patients undergoing elective, noncardiac, nonvascular surgery 3.

From the Research

Anaemia with Normal Iron Studies

• Anaemia is a common condition that can be caused by various factors, including iron deficiency, vitamin B12 deficiency, and folate deficiency 4.
• The diagnosis of anaemia is typically made through a complete blood count (CBC) and physical examination, with supplemental tests such as iron panel, vitamin B12, and folate levels to determine the underlying cause 5.
• In cases where iron studies are normal, other causes of anaemia should be considered, such as vitamin B12 or folate deficiency, which can be diagnosed through laboratory tests 4, 6.
• Treatment of anaemia depends on the underlying cause, and may involve supplementation with iron, vitamin B12, or folate, as well as addressing any underlying conditions that may be contributing to the anaemia 7, 8.

Laboratory Tests

• A full blood count is the first-line laboratory test for suspected anaemia, and may suggest a nutritional deficiency of iron, vitamin B12, or folate 4.
• Additional tests, such as iron panel, vitamin B12, and folate levels, can help determine the underlying cause of anaemia 5.
• A peripheral blood smear and reticulocyte count may also be useful in evaluating anaemia 5.

Relationship between Iron and Other Nutrients

• Iron deficiency has been shown to affect vitamin B12 and folate levels, with treatment of iron deficiency anaemia resulting in increased levels of these nutrients 8.
• Folate, vitamin B12, and iron all play crucial roles in erythropoiesis, and deficiencies in any of these nutrients can lead to anaemia 6.