Additional Laboratory Tests for Anemia Evaluation
When evaluating a patient with anemia, a comprehensive laboratory workup should include complete blood count with indices, reticulocyte count, serum ferritin, transferrin saturation, and C-reactive protein as the minimum initial tests. 1
Initial Laboratory Assessment
Complete Blood Count (CBC) including:
- Hemoglobin concentration
- Red cell indices (MCV, MCH, MCHC)
- Red cell distribution width (RDW)
- White blood cell count and differential
- Platelet count
Reticulocyte count - critical for distinguishing between production defects and blood loss/hemolysis 1, 2
Iron studies:
- Serum ferritin
- Transferrin saturation (TSAT)
- Consider soluble transferrin receptor in inflammatory states 1
Inflammatory marker: C-reactive protein (CRP) 1
Additional Testing Based on Initial Results
For Microcytic Anemia (MCV <80 fL)
- Serum iron
- Total iron binding capacity
- Hemoglobin electrophoresis (if thalassemia suspected)
- Lead levels (particularly in children)
For Normocytic Anemia (MCV 80-100 fL)
- Renal function tests (BUN, creatinine)
- Liver function tests
- Thyroid function tests
- Lactate dehydrogenase (LDH)
- Haptoglobin (if hemolysis suspected)
- Direct antiglobulin test (Coombs test) for immune hemolysis 1
For Macrocytic Anemia (MCV >100 fL)
- Vitamin B12 level
- Folate level
- Methylmalonic acid (more sensitive for B12 deficiency)
- Homocysteine level
- Liver function tests
- Thyroid function tests
- Reticulocyte hemoglobin content 1
Special Considerations
For Suspected Bone Marrow Disorders
- Peripheral blood smear examination
- Bone marrow aspiration and biopsy (if myelodysplastic syndrome or aplastic anemia suspected)
For Suspected Gastrointestinal Blood Loss
- Fecal occult blood testing
- Non-invasive testing for H. pylori and celiac disease before endoscopy 1
For Suspected Chronic Disease/Inflammation
- When ferritin is 30-100 ng/mL with low TSAT (<20%), consider combination of true iron deficiency and anemia of chronic disease 1
- Percentage of hypochromic red cells may help distinguish 1
For Inadequate Response to Iron Therapy
- Consider evaluation for additional causes of anemia 1, 2
- Small bowel evaluation (capsule endoscopy or CT/MR enterography) 2
Monitoring Response to Therapy
- Check hemoglobin response within 4 weeks of starting iron therapy 2
- Expected rise in hemoglobin is approximately 2 g/dL after 3-4 weeks 2
- Monitor hemoglobin and MCV at 3-month intervals for one year, then again at 2 years 2
Important Pitfalls to Avoid
- Don't rely solely on MCV for classification: Concurrent conditions can mask typical MCV changes (e.g., iron deficiency with B12 deficiency can result in normal MCV)
- Don't overlook inflammation: Ferritin is an acute phase reactant; levels up to 100 ng/mL may still indicate iron deficiency in inflammatory states 1
- Don't assume minor GI findings explain significant anemia: Hemorrhoids or diverticulosis are often incidental and not the cause of significant iron deficiency anemia 2
- Don't stop at negative bidirectional endoscopy: Up to 30-50% of patients with iron deficiency anemia have upper GI sources of blood loss, and small bowel pathology may be present in those with negative initial evaluation 2
By following this systematic approach to laboratory testing in anemia, clinicians can efficiently identify the underlying cause and implement appropriate treatment to improve patient outcomes.