Recommended Investigations for Anemia
The initial evaluation of anemia should include complete blood count with red cell indices, reticulocyte count, serum ferritin, transferrin saturation, vitamin B12 and folate levels to determine the underlying cause and guide appropriate treatment. 1
Initial Laboratory Investigations
Complete blood count (CBC) - Essential first-line test that includes:
- Hemoglobin concentration
- Red cell indices (MCV, MCH, MCHC)
- White blood cell count with differential
- Platelet count 1
Absolute reticulocyte count - Helps distinguish between inadequate production versus increased destruction or loss of red blood cells 1
Serum ferritin - The single most useful marker for iron deficiency; levels <15 μg/L indicate absent iron stores 1
Transferrin saturation (TSAT) - Particularly helpful when ferritin may be falsely normal due to inflammation 1
Serum vitamin B12 and folate levels - Essential to rule out megaloblastic anemia 1
Morphological Assessment
- Peripheral blood smear examination - Provides valuable information about red cell morphology, which can suggest specific diagnoses 2, 3
- Microcytosis suggests iron deficiency, thalassemia
- Macrocytosis suggests vitamin B12/folate deficiency, liver disease
- Fragmented cells suggest hemolysis 2
Additional Tests Based on Initial Results
For Microcytic Anemia:
- Iron studies (if not already done):
- Serum iron
- Total iron binding capacity (TIBC)
- Transferrin saturation 1
- Hemoglobin electrophoresis - If thalassemia is suspected, particularly in patients with microcytosis and normal iron studies 1
For Macrocytic Anemia:
- Liver function tests - To evaluate for liver disease 3
- Thyroid function tests - To rule out hypothyroidism 3
- Lactate dehydrogenase (LDH) - Elevated in megaloblastic anemia and hemolysis 3
For Suspected Hemolysis:
- Haptoglobin - Decreased in hemolysis 3
- LDH and bilirubin - Elevated in hemolysis 3
- Direct antiglobulin test (Coombs test) - To detect immune-mediated hemolysis 3
Specific Investigations for Iron Deficiency Anemia
Iron deficiency anemia (IDA) requires investigation of the underlying cause, particularly in men and postmenopausal women where gastrointestinal blood loss is common:
Urinalysis or urine microscopy - To detect hematuria 1
Celiac disease screening - Found in 3-5% of IDA cases 1
- Serological testing (anti-tissue transglutaminase antibodies)
- Or small bowel biopsy during gastroscopy
Gastrointestinal evaluation - For men and postmenopausal women:
- Gastroscopy and colonoscopy as first-line GI investigations
- CT colonography for those unsuitable for colonoscopy 1
Small bowel evaluation - If bidirectional endoscopy is negative:
- Capsule endoscopy (preferred method)
- CT/MR enterography as alternatives 1
Practical Approach to Anemia Investigation
Confirm anemia - Compare hemoglobin to age and sex-specific reference ranges 1
Classify based on MCV:
Assess reticulocyte count:
- Low: Suggests inadequate bone marrow production
- High: Suggests hemolysis or blood loss 2
Evaluate iron status - Particularly important as iron deficiency is the most common cause of anemia worldwide 2, 4
Investigate underlying cause based on classification and clinical context 1
Common Pitfalls to Avoid
Relying solely on MCV - Iron deficiency may initially present as normocytic before becoming microcytic 1
Misinterpreting ferritin levels - Ferritin is an acute phase reactant and may be falsely normal or elevated in inflammatory states, malignancy, or liver disease 1
Incomplete investigation - Failure to investigate the cause of iron deficiency anemia, particularly in men and postmenopausal women where GI malignancy may be present 1
Premature treatment - Starting iron replacement before appropriate investigations may mask underlying pathology 1
Overlooking combined deficiencies - Multiple nutritional deficiencies can coexist and affect red cell indices 1