What labs are recommended to diagnose and determine the type of anemia?

Diagnostic Approach to Anemia

The essential laboratory workup for diagnosing and determining the type of anemia should include a complete blood count with indices, reticulocyte count, serum ferritin, transferrin saturation, and C-reactive protein. 1

Initial Laboratory Assessment

• Complete Blood Count (CBC) with indices - provides hemoglobin level, hematocrit, red blood cell count, and red cell indices including Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin (MCH), and Mean Corpuscular Hemoglobin Concentration (MCHC) 2
• Reticulocyte count - essential to assess bone marrow response to anemia 2
• Peripheral blood smear review - critical to confirm the size, shape, and color of RBCs 2
• Serum ferritin - primary marker for tissue iron stores 2
• Transferrin saturation - represents iron available to bone marrow for erythropoiesis 2
• C-reactive protein (CRP) - helps assess presence of inflammation which affects interpretation of iron studies 2

Classification by MCV (Morphologic Approach)

Microcytic Anemia (MCV < 80 fL)

• Iron studies (serum ferritin, transferrin saturation, TIBC) - to diagnose iron deficiency 2
• Hemoglobin electrophoresis - if thalassemia is suspected 2
• Red cell distribution width (RDW) - elevated in iron deficiency 2, 3

Normocytic Anemia (MCV 80-100 fL)

• Reticulocyte count - key follow-up test 2
  • Low reticulocyte count suggests decreased production (bone marrow failure, anemia of chronic inflammation, renal insufficiency) 2, 4
  • High reticulocyte count suggests blood loss or hemolysis 2
• For suspected hemolysis: haptoglobin, lactate dehydrogenase (LDH), and bilirubin 2, 4

Macrocytic Anemia (MCV > 100 fL)

• Vitamin B12 and folate levels 2, 5
• Thyroid function tests - hypothyroidism can cause macrocytosis 1
• Liver function tests - liver disease can cause macrocytosis 1

Classification by Mechanism (Kinetic Approach)

Reticulocyte Index (RI) Assessment

• Calculate RI to correct reticulocyte count for degree of anemia 2
• Normal RI ranges between 1.0 and 2.0 2

Low RI (Decreased Production)

• Iron studies (ferritin, transferrin saturation) 2
• Vitamin B12 and folate levels 2
• Consider bone marrow examination if other tests inconclusive 1

High RI (Increased Destruction or Loss)

• Hemolysis workup: haptoglobin, LDH, bilirubin 2, 4
• Assess for blood loss: occult blood testing, endoscopy if indicated 6

Special Considerations for Iron Deficiency

• Diagnostic criteria depend on inflammation status 2
• Without inflammation: serum ferritin < 30 μg/L confirms iron deficiency 2
• With inflammation: serum ferritin up to 100 μg/L may still indicate iron deficiency 2
• Transferrin saturation < 20% with ferritin > 100 μg/L suggests anemia of chronic disease 2
• Ferritin between 30-100 μg/L with low transferrin saturation suggests combined iron deficiency and anemia of chronic disease 2

Pitfalls and Caveats

• CBC parameters alone without iron studies may miss iron deficiency 6
• Ferritin is an acute phase reactant and may be elevated despite iron deficiency in inflammatory states 2
• Mixed anemias can present with normal MCV despite underlying deficiencies 3
• Early iron deficiency may present with normal hemoglobin and hematocrit but reduced iron stores 6
• High RDW with normal MCV may be an early indicator of developing iron deficiency 7, 3
• Reticulocyte count must be interpreted in context of the degree of anemia 2

By following this systematic approach to anemia diagnosis, clinicians can accurately determine the type of anemia and provide appropriate treatment, ultimately improving patient outcomes related to morbidity, mortality, and quality of life.