How are anemias categorized?

Anemia Classification

Anemias are categorized using a two-step approach: first by mean corpuscular volume (MCV) to classify as microcytic, normocytic, or macrocytic, then by reticulocyte count to distinguish between decreased production versus increased destruction or loss of red blood cells. 1

Primary Classification by MCV

Microcytic Anemia (MCV <80 fL)

• Iron deficiency anemia is the most common cause of microcytic anemia 1, 2
• Anemia of chronic disease can present with microcytic features in 30-50% of cases, though it is normocytic in 50-70% 1, 3
• Thalassemia and sideroblastic anemia represent hereditary causes that should be suspected when ferritin is elevated, family history is present, or anemia is refractory to iron supplementation 1
• Lead poisoning is a rare but important consideration 1

Normocytic Anemia (MCV 80-100 fL)

• Acute hemorrhage presents with normocytic anemia initially 1, 2
• Hemolysis causes normocytic anemia with elevated reticulocytes 2
• Renal anemia develops when GFR falls below 20-30 mL/min due to erythropoietin deficiency 2
• Anemia of chronic disease/inflammation associated with cancer, infection, and inflammatory conditions 1, 3
• Bone marrow failure including aplastic anemia and myelodysplastic syndromes 1, 2

Macrocytic Anemia (MCV >100 fL)

• Vitamin B12 deficiency is a primary nutritional cause 1, 2
• Folate deficiency produces similar macrocytic changes 1, 2
• Medication-induced anemia from drugs like hydroxyurea and antiretrovirals 1, 4
• Myelodysplastic syndrome and myeloma 2, 4
• Alcoholism and hypothyroidism are additional causes 2, 4

Secondary Classification by Reticulocyte Count

Low or Normal Reticulocyte Count (Decreased Production)

• Nutritional deficiencies including iron, B12, and folate 1, 2
• Bone marrow failure from aplastic anemia or infiltrative processes 1
• Chronic disease with inflammatory cytokine suppression 1, 2
• Renal insufficiency with inadequate erythropoietin 1

High Reticulocyte Count (Increased Destruction or Loss)

• Hemolysis from hereditary spherocytosis, enzyme deficiencies, hemoglobinopathies, or autoimmune causes 1, 5
• Acute blood loss with appropriate marrow response 1, 2
• Hemoglobinopathies such as thalassemia may present with microcytosis and elevated reticulocytes 1

Combined Classification Algorithm

For microcytic anemia:

• Low/normal reticulocytes → iron deficiency, anemia of chronic disease, lead poisoning, hereditary anemias 1
• High reticulocytes → hemoglobinopathies like thalassemia 1

For normocytic anemia:

• Low/normal reticulocytes → acute hemorrhage (early), renal anemia, anemia of chronic disease, bone marrow failure 1
• High reticulocytes → hemolysis, acute blood loss (later phase) 2

For macrocytic anemia:

• Low/normal reticulocytes → B12/folate deficiency, myelodysplastic syndrome, medications, hypothyroidism 1
• High reticulocytes → hemolysis with macrocytic features 2

Essential Initial Diagnostic Workup

The initial evaluation must include: 1, 3, 2

• Complete blood count with MCV and red cell distribution width (RDW)
• Reticulocyte count (corrected for degree of anemia)
• Serum ferritin and transferrin saturation
• C-reactive protein or ESR to assess for inflammation
• Renal function tests (creatinine and GFR)
• Peripheral blood smear for morphologic evaluation

Critical Diagnostic Pitfalls

Combined deficiency states (iron plus B12/folate) may result in a normal MCV, masking both deficiencies 2

Functional iron deficiency in chronic disease can occur with low-normal ferritin (30-100 μg/L) but low transferrin saturation (<20%), requiring iron studies interpretation in context of inflammation 1, 2

High RDW in normocytic anemia suggests underlying iron deficiency or mixed deficiency states 2

Ferritin interpretation varies with inflammation: <30 μg/L indicates iron deficiency without inflammation, but up to 100 μg/L may represent deficiency when inflammation is present 2

Early nutritional deficiencies may initially present as normocytic before morphological changes become apparent 2