Main Classifications of Anemia
Anemia can be most effectively classified using a combination of mean corpuscular volume (MCV) and reticulocyte count, which provides crucial information about both the type of anemia and the bone marrow's response to it. 1
Classification Based on MCV
Anemia is primarily categorized by red blood cell size:
1. Microcytic Anemia (MCV < 80 fL)
- Iron deficiency anemia - most common cause of microcytic anemia 1
- Anemia of chronic disease (cancer, infection, inflammatory conditions) 1
- Lead poisoning (rare) 1
- Hereditary microcytic anemia (thalassemia, sideroblastic anemia) 1, 2
2. Normocytic Anemia (MCV 80-100 fL)
- Acute hemorrhage - may initially show elevated reticulocytes 1
- Renal anemia - characterized by inappropriately low erythropoietin levels 1
- Anemia of chronic disease/inflammation 1, 3
- Bone marrow failure (aplastic anemia, pure red cell aplasia) 1, 2
- Primary bone marrow diseases (leukemias, myelodysplastic syndrome) 1
- Bone marrow infiltration by cancer (prostate, breast) 1
3. Macrocytic Anemia (MCV > 100 fL)
- Vitamin B12 deficiency (pernicious anemia, H. pylori gastritis, veganism) 1, 4
- Folate deficiency (increased requirements in pregnancy, hemolysis) 1, 4
- Myelodysplastic syndrome 1, 5
- Medication-induced (hydroxyurea, methotrexate, azathioprine) 1, 4
- Alcoholism 1, 5
- Hypothyroidism 1, 4
Classification Based on Reticulocyte Count
The reticulocyte count provides critical information about bone marrow response:
1. Low/Normal Reticulocyte Count (Decreased Production)
- Indicates impaired bone marrow production of red blood cells 1, 6
- Common in nutritional deficiencies, bone marrow failure, and chronic disease 1
2. High Reticulocyte Count (Increased Destruction/Loss)
- Indicates normal or increased bone marrow production with peripheral destruction or loss 1, 6
- Common in hemolysis and acute blood loss 1
Combined Classification Approach
The most effective diagnostic approach combines both MCV and reticulocyte count:
Microcytic Anemia with Low/Normal Reticulocytes
- Iron deficiency, anemia of chronic disease, lead poisoning, hereditary anemias 1
Microcytic Anemia with High Reticulocytes
- Hemoglobinopathies (thalassemia) 1
Normocytic Anemia with Low/Normal Reticulocytes
- Acute hemorrhage, renal anemia, anemia of chronic disease, bone marrow failure 1
Normocytic Anemia with High Reticulocytes
Macrocytic Anemia with Low/Normal Reticulocytes
Macrocytic Anemia with High Reticulocytes
- Hemolysis (false macrocytosis), MDS with hemolysis 1
Important Clinical Considerations
- Overlapping presentations: Mixed deficiency states can neutralize MCV abnormalities, resulting in a normal MCV despite underlying pathology 1, 7
- Red cell distribution width (RDW): A high RDW can help identify iron deficiency when microcytosis and macrocytosis coexist 1, 6
- Inflammation impact: In inflammatory conditions, ferritin levels may be elevated despite iron deficiency, potentially masking concurrent iron deficiency 1, 4
- Diagnostic limitations: Recent research suggests that MCV-guided classification alone may lead to incorrect exclusion of certain anemia etiologies; broader laboratory testing is recommended 7
Initial Diagnostic Workup
Minimum initial workup should include:
- Complete blood count with MCV
- Reticulocyte count
- Serum ferritin
- Transferrin saturation
- C-reactive protein 1, 6
Additional testing based on initial results may include vitamin B12, folate, haptoglobin, LDH, bilirubin, and bone marrow examination 1, 4