What tests to consider in a patient with anemia (Hemoglobin (Hb) 7.4 g/dL), normal Mean Corpuscular Volume (MCV), iron deficiency (low iron), normal Total Iron-Binding Capacity (TIBC), elevated ferritin (55 ng/mL), and peripheral edema (lower extremity swelling)?

From the Guidelines

For a patient with hemoglobin of 7.4 g/dL, normal MCV, low iron, normal TIBC, ferritin of 55, and lower extremity swelling, I recommend obtaining a complete blood count with differential, peripheral blood smear, and additional iron studies including reticulocyte count and haptoglobin to further characterize the anemia and distinguish between iron deficiency and anemia of chronic disease. Given the patient's ferritin level of 55, which is above the cutoff of 45 ng/mL recommended by the AGA for diagnosing iron deficiency anemia 1, it is essential to consider other potential causes of anemia. The normal TIBC and low iron levels may indicate anemia of chronic disease, which can be associated with inflammation, chronic kidney disease, or other underlying conditions.

To evaluate the patient's anemia, consider the following tests:

• Complete blood count with differential to further characterize the anemia
• Peripheral blood smear to evaluate red cell morphology and rule out hemolysis
• Additional iron studies including reticulocyte count and haptoglobin to distinguish between iron deficiency and anemia of chronic disease
• Kidney function tests, such as BUN, creatinine, and urinalysis, to assess for potential renal insufficiency
• Cardiac evaluation with BNP, ECG, and echocardiogram to evaluate for heart failure
• Liver function tests to assess for hepatic disease
• Inflammatory markers, such as CRP and ESR, to evaluate for underlying inflammation
• Hemoglobin electrophoresis to rule out hemoglobinopathies

The lower extremity swelling could indicate heart failure, liver disease, kidney disease, or venous insufficiency, all of which can complicate anemia management. According to the AGA guidelines, bidirectional endoscopy may be considered in patients with iron deficiency anemia, especially if there is a suspicion of gastrointestinal bleeding or malignancy 1. However, in this case, the patient's ferritin level is above the recommended cutoff, and other causes of anemia should be explored first. The KDIGO guidelines recommend evaluating anemia in patients with chronic kidney disease using a complete blood count, reticulocyte count, serum ferritin, and TSAT 1.

In this patient, it is crucial to balance the potential benefits of diagnostic tests against the risks of harm and to prioritize tests that will provide the most valuable information for managing the patient's anemia and underlying conditions. The most critical step is to identify the underlying cause of the anemia and to address any potential complications or comorbidities, such as heart failure, liver disease, or kidney disease, which can impact the patient's morbidity, mortality, and quality of life.

From the Research

Diagnostic Considerations

Given the patient's presentation with Hgb 7.4, normal MCV, low iron, normal TIBC, ferritin 55, and lower extremity swelling, several tests can be considered to further evaluate the cause of anemia and guide management:

• Reticulocyte hemoglobin content (CHr) to assess iron availability and diagnose iron deficiency anemia, as it is less affected by inflammation compared to serum iron, transferrin saturation, and ferritin 2
• Complete blood count (CBC) with reticulocyte count to evaluate bone marrow response and detect any underlying hematological disorders
• Serum soluble transferrin receptor to differentiate between iron deficiency anemia and anemia of chronic disease
• Bone marrow examination, although invasive and costly, can provide a definitive diagnosis of iron deficiency and iron deficiency anemia 2

Role of Reticulocyte Hemoglobin Content

Reticulocyte hemoglobin content (CHr) has been shown to be a useful marker for diagnosing iron deficiency anemia, particularly in patients with cancer 3. A cut-off value of 28.4 pg has been proposed to rule out iron deficient erythropoiesis, with a sensitivity of 96.77% and specificity of 81.66% 3. CHr can also be used to monitor response to iron therapy and guide treatment decisions 2.

Additional Evaluations

In patients with lower extremity swelling, additional evaluations may be necessary to rule out underlying conditions such as:

• Cardiovascular disease
• Renal disease
• Liver disease
• Nutritional deficiencies (e.g., vitamin B12, folate)
• Chronic inflammatory conditions (e.g., rheumatoid arthritis, chronic infections)