What is the workup for anemia of chronic disease?

From the Guidelines

The workup for anemia of chronic disease involves a comprehensive approach to confirm the diagnosis and rule out other causes of anemia, with initial evaluation including a complete blood count (CBC) with differential, peripheral blood smear, reticulocyte count, and iron studies, as recommended by the most recent guidelines 1.

Initial Evaluation

The initial evaluation should include:

• Complete blood count (CBC) with differential
• Peripheral blood smear
• Reticulocyte count
• Iron studies including serum iron, total iron binding capacity (TIBC), transferrin saturation, and ferritin Characteristic findings include normocytic or mildly microcytic anemia, low serum iron, low TIBC, low transferrin saturation (typically <20%), and normal or elevated ferritin levels.

Additional Testing

Additional testing should assess for underlying chronic conditions that may be causing the anemia, such as:

• Inflammatory markers (ESR, CRP)
• Renal function tests (BUN, creatinine)
• Liver function tests
• Specific tests for suspected underlying diseases like rheumatoid factor or other autoimmune markers Soluble transferrin receptor (sTfR) measurement and calculation of the sTfR/log ferritin index can help differentiate anemia of chronic disease from iron deficiency anemia, particularly in cases where they coexist.

Bone Marrow Examination

Bone marrow examination is rarely necessary but may be considered in complex cases to evaluate iron stores and rule out other bone marrow disorders.

Treatment

Treatment primarily focuses on addressing the underlying chronic condition rather than the anemia itself, though in severe cases, erythropoiesis-stimulating agents may be considered, as discussed in the recent KDIGO conference 1.

The most recent study 1 emphasizes the importance of re-examining previous recommendations and exploring new controversies in anemia management, highlighting the need for a comprehensive approach to diagnosis and treatment.

From the FDA Drug Label

Correct or exclude other causes of anemia (e. g., vitamin deficiency, metabolic or chronic inflammatory conditions, bleeding, etc.) before initiating Aranesp. 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 workup for anemia of chronic disease includes:

• Correcting or excluding other causes of anemia, such as vitamin deficiency, metabolic or chronic inflammatory conditions, and bleeding
• Evaluating iron status before and during treatment
• Administering supplemental iron therapy when serum ferritin is less than 100 mcg/L or when serum transferrin saturation is less than 20% 2

From the Research

Workup for Anemia of Chronic Disease

The workup for anemia of chronic disease involves a series of diagnostic tests to determine the underlying cause of the anemia. The following are some of the key components of the workup:

• Examination of changes in serum iron parameters, including low to normal serum iron, transferrin saturation, and transferrin concentrations 3
• Measurement of ferritin levels, which are often normal to increased in anemia of chronic disease 3, 4
• Assessment of zinc protoporphyrin IX and cytokine levels, which can be elevated in anemia of chronic disease 3
• Ruling out iron deficiency and other causes of anemia, as misdiagnosis can lead to refractoriness to standard therapy 5
• Evaluation of the patient's ferrokinetic state and correlation with the possible clinical pathways of the underlying disease 5

Diagnostic Criteria

The diagnosis of anemia of chronic disease can be assessed by the following criteria:

• Low to normal serum iron and transferrin saturation 3, 4
• Normal to increased ferritin levels 3, 4
• Elevated zinc protoporphyrin IX and cytokine levels 3
• Presence of an underlying chronic disease, such as chronic infection, cancer, or autoimmune disease 3, 5

Laboratory Tests

The following laboratory tests may be ordered as part of the workup for anemia of chronic disease:

• Complete blood count (CBC) to evaluate hemoglobin levels and red blood cell indices 6, 7
• Serum iron, total iron binding capacity, and transferrin saturation to assess iron status 3, 4
• Ferritin levels to evaluate iron stores 3, 4
• Zinc protoporphyrin IX and cytokine levels to assess the inflammatory response 3
• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) to evaluate inflammation 6