Anemia Classification
Anemia is classified primarily by mean corpuscular volume (MCV) into microcytic, normocytic, and macrocytic categories, with reticulocyte count providing critical information about bone marrow response and directing the diagnostic pathway. 1, 2
Primary Classification System
By Red Blood Cell Size (MCV)
Microcytic Anemia (MCV < 83 fL)
- Iron deficiency anemia - the most common cause of microcytic anemia, diagnosed by serum ferritin <30 μg/L in the absence of inflammation 1, 3
- Anemia of chronic disease - can present as microcytic, particularly in inflammatory states where ferritin up to 100 μg/L may still indicate iron deficiency 1
- Thalassemia and hemoglobinopathies - hereditary causes identified through hemoglobin electrophoresis and family history 1
- Lead poisoning (rare) and hereditary microcytic anemias 1
Normocytic Anemia (MCV 83-100 fL)
- Acute hemorrhage - may initially show elevated reticulocytes 1, 2
- Renal anemia - characterized by inappropriately low endogenous erythropoietin levels 1
- Anemia of chronic disease - most common cause of normocytic anemia, showing normal or elevated ferritin, low iron, low TIBC, and low transferrin saturation 1, 2
- Bone marrow disorders - including severe aplastic anemia, pure red cell aplasia, leukemias, and myelodysplastic syndromes 1
- Bone marrow infiltration by malignancy (prostate, breast) 1
Macrocytic Anemia (MCV > 100 fL)
- Vitamin B12 deficiency - from pernicious anemia, H. pylori gastritis, antacids, or vegan diet 1, 4
- Folate deficiency - increased requirement in pregnancy, hemolysis, or chronic conditions 1, 4
- Myelodysplastic syndrome 1, 4
- Medications - hydroxyurea, azathioprine, phenytoin, antiretroviral drugs 4, 5
- Alcohol use, thyroid disease, liver disease 4, 5
By Reticulocyte Response
The reticulocyte count distinguishes whether bone marrow can respond appropriately to anemia 1, 2:
Low or Normal Reticulocyte Index (<2.0) - Production Defect
- Indicates bone marrow dysfunction, anemia of chronic disease/inflammation, renal insufficiency, or early nutritional deficiencies 2
- All deficiency states are excluded by increased reticulocytes 1
- Requires evaluation with inflammatory markers, iron studies, renal function, thyroid function, and vitamin B12/folate levels 2
Elevated Reticulocyte Index (>2.0) - Appropriate Marrow Response
- Points toward hemolysis or acute blood loss 1, 2
- Requires hemolysis panel including indirect bilirubin, lactate dehydrogenase, haptoglobin, direct antiglobulin test, and free hemoglobin 2
Severity Grading
By Hemoglobin Concentration 1:
- Mild anemia: Hemoglobin ≤11.9 g/dL and ≥10 g/dL
- Moderate anemia: Hemoglobin ≤9.9 g/dL and ≥8.0 g/dL
- Severe anemia: Hemoglobin <8.0 g/dL
Critical Diagnostic Pitfalls
Mixed Deficiencies
- Combined iron and B12 deficiency can neutralize MCV changes, presenting as normocytic when both microcytic and macrocytic processes coexist 2, 4
- Elevated RDW (>15%) is the critical clue to this dual pathology 2, 4
Ferritin Interpretation in Inflammation
- Ferritin is an acute-phase reactant and can be falsely elevated during illness or stress, masking iron deficiency 1
- In inflammatory states, ferritin up to 100 μg/L may still be consistent with iron deficiency 1
- Without inflammation, ferritin <30 μg/L indicates iron deficiency 1
Pseudoanemia in Athletes
- Iron studies may indicate anemia but laboratory values result from expanded plasma volume rather than true iron deficiency 1
Essential Initial Workup
First-Line Laboratory Tests 2:
- Complete blood count with red cell indices (MCV, RDW)
- Peripheral blood smear examination
- Reticulocyte count corrected for anemia severity
- Basic metabolic panel including creatinine and blood urea nitrogen
Additional Tests Based on MCV and Reticulocyte Pattern 1, 2:
- Iron studies (serum iron, ferritin, transferrin saturation, total iron binding capacity)
- Vitamin B12 and folate levels
- Inflammatory markers (CRP, ESR)
- Hemoglobin electrophoresis (if thalassemia suspected)
- Hemolysis panel (if reticulocytes elevated)