Types of Anemia
Anemia is classified into three main categories based on mean corpuscular volume (MCV): microcytic (MCV <80 fL), normocytic (MCV 80-100 fL), and macrocytic (MCV >100 fL), with further subcategorization based on reticulocyte count to determine whether the anemia results from decreased red blood cell production or increased destruction/loss. 1
Microcytic Anemia (MCV <80 fL)
With Low or Normal Reticulocyte Count (Decreased Production)
- Iron deficiency anemia is the most common cause of microcytic anemia and represents the most frequent anemia type overall 1, 2
- Anemia of chronic disease/inflammation occurs in 50-70% of cases as normocytic but can present as microcytic, associated with cancer, infection, and inflammatory conditions 1, 3
- Lead poisoning should be considered as a rare cause 1
- Hereditary microcytic anemias include thalassemia and sideroblastic anemia, which should be suspected when ferritin is elevated or transferrin saturation is abnormal, family history is present, or anemia is refractory to iron supplementation 4, 1
With High Reticulocyte Count (Increased Destruction)
- Hemoglobinopathies such as thalassemia syndromes can present with elevated reticulocytes 1
Normocytic Anemia (MCV 80-100 fL)
With Low or Normal Reticulocyte Count (Decreased Production)
- Acute hemorrhage in the early phase before MCV changes occur 1, 3
- Chronic kidney disease causing renal anemia through decreased erythropoietin production 1, 3
- Anemia of chronic disease is normocytic in 50-70% of cases 3
- Bone marrow failure including aplastic anemia, myelodysplastic syndromes, and bone marrow infiltration by malignancy 1, 5
With High Reticulocyte Count (Increased Destruction/Loss)
- Hemolytic anemias including hereditary spherocytosis, enzyme deficiencies (G6PD deficiency), autoimmune hemolytic anemia, and paroxysmal nocturnal hemoglobinuria 1, 5
- Acute blood loss with compensatory reticulocytosis 1
Macrocytic Anemia (MCV >100 fL)
With Low or Normal Reticulocyte Count (Decreased Production)
- Vitamin B12 deficiency is a primary cause of megaloblastic macrocytic anemia and should be the first consideration 6
- Folate deficiency is another common cause of megaloblastic anemia 1, 6
- Medication-induced anemia from hydroxyurea, methotrexate, azathioprine, and antiretroviral drugs 1, 6
- Myelodysplastic syndrome particularly in older adults 1, 6
- Hypothyroidism can cause macrocytic anemia 6
- Chronic alcohol use causes macrocytosis and may impair B12 absorption 6
With High Reticulocyte Count (Increased Destruction/Loss)
- Hemolysis with compensatory reticulocytosis causing macrocytosis from young red blood cells 6
- Recent hemorrhage with reticulocyte response 6
Critical Diagnostic Approach
The initial workup must include complete blood count with MCV, reticulocyte count (corrected), serum ferritin, transferrin saturation, and C-reactive protein to properly classify the anemia type and guide further evaluation. 1, 3
Key Diagnostic Pitfalls to Avoid
- Mixed anemias can present with normal MCV when microcytosis and macrocytosis coexist—an elevated red cell distribution width (RDW) helps identify this scenario 6
- Ferritin elevation in inflammatory conditions may mask concurrent iron deficiency despite elevated levels, requiring transferrin saturation assessment 6
- Functional iron deficiency in chronic disease can occur with low-normal ferritin (>20 mg/L) but low transferrin saturation 4
- Vitamin B12 deficiency must be treated before folate supplementation to prevent precipitating subacute combined degeneration of the spinal cord 6