Follow-up Tests for Anemia
The essential follow-up tests for anemia include complete blood count with red cell indices, reticulocyte count, serum ferritin, transferrin saturation, and C-reactive protein, followed by more targeted testing based on these initial results. 1
Initial Laboratory Evaluation
Basic Testing (Required for All Anemic Patients)
- Complete blood count (CBC) with:
- Hemoglobin level
- Mean corpuscular volume (MCV)
- Red cell distribution width (RDW)
- Reticulocyte count
- Serum ferritin
- Transferrin saturation (TSAT)
- C-reactive protein (CRP)
Morphologic Classification Based on MCV
Microcytic (MCV < 80 fL):
- Most commonly caused by iron deficiency
- Other causes: thalassemia, anemia of chronic disease, sideroblastic anemia 1
Normocytic (MCV 80-100 fL):
- May be caused by hemorrhage, hemolysis, bone marrow failure, anemia of chronic inflammation, renal insufficiency 1
Macrocytic (MCV > 100 fL):
- Megaloblastic: vitamin B12 or folate deficiency
- Non-megaloblastic: alcoholism, myelodysplastic syndrome (MDS), certain drugs 1
Secondary Testing Based on Initial Results
For Suspected Iron Deficiency (Microcytic Anemia)
- Total iron binding capacity (TIBC)
- Percentage of hypochromic red cells (if available)
- Stool guaiac test for occult blood 1
For Suspected Vitamin Deficiency (Macrocytic Anemia)
- Serum vitamin B12 levels
- Serum folate levels 1
For Suspected Hemolysis
- Lactate dehydrogenase (LDH)
- Haptoglobin
- Indirect bilirubin
- Coombs test 1
For Suspected Renal Disease
- Serum creatinine
- Glomerular filtration rate (GFR)
- Erythropoietin level 1
Specialized Testing for Specific Scenarios
For Cancer-Related Anemia
- Bone marrow biopsy (if bone marrow dysfunction suspected)
- Reticulocyte hemoglobin content (CHr) - if available 1
For Chronic Kidney Disease
- Serum creatinine
- White blood cell and platelet counts (to assess for generalized bone marrow dysfunction) 1
For Inflammatory Bowel Disease
- Percentage of hypochromic red cells
- Soluble transferrin receptor 1
Interpretation Algorithm
Assess Iron Status:
- Absolute iron deficiency: ferritin < 30 ng/mL, TSAT < 15%
- Functional iron deficiency: normal/high ferritin with TSAT < 20%
- Iron overload: ferritin > 800 ng/mL, TSAT > 50% 1
Evaluate Reticulocyte Response:
- Low reticulocyte index (< 1.0): indicates decreased RBC production (iron deficiency, vitamin deficiency, bone marrow dysfunction)
- High reticulocyte index (> 2.0): indicates blood loss or hemolysis 1
Assess for Chronic Disease/Inflammation:
- Elevated CRP with normal/high ferritin but low TSAT suggests anemia of chronic disease 1
Monitoring After Diagnosis and Treatment
- For iron deficiency anemia: Monitor hemoglobin and MCV every three months for one year, then after another year 1
- For vitamin B12 deficiency: Monitor hematocrit and reticulocyte counts daily from the fifth to seventh days of therapy until hematocrit normalizes 2
- For cancer-related anemia: Consider repeating iron studies 3-4 weeks after iron therapy 1
Common Pitfalls to Avoid
Relying solely on hemoglobin: An isolated hemoglobin measurement has both low specificity and sensitivity for determining the cause of anemia 3
Misinterpreting ferritin in inflammatory states: Inflammation can elevate ferritin despite iron deficiency; consider transferrin saturation and CRP when interpreting ferritin levels 1
Overlooking occult blood loss: Always consider gastrointestinal blood loss in iron deficiency anemia, especially in men and postmenopausal women 4
Neglecting vitamin B12 testing in macrocytic anemia: Failure to diagnose B12 deficiency can lead to irreversible neurological damage even if anemia is treated with folic acid 2
By following this systematic approach to anemia evaluation, clinicians can efficiently identify the underlying cause and implement appropriate treatment strategies to address both the anemia and its root cause.