What are the different types of anemia and their corresponding laboratory findings?

Anemia Classification and Laboratory Findings

Anemia is classified primarily by mean corpuscular volume (MCV) and reticulocyte index, which together identify the underlying mechanism and guide targeted diagnostic workup. 1, 2

Morphologic Classification by MCV

Microcytic Anemia (MCV < 80 fL)

• Iron deficiency anemia is the most common cause, confirmed by serum ferritin <30 μg/L (without inflammation), transferrin saturation <15-20%, and elevated red cell distribution width (RDW) 3, 1, 2
• Anemia of chronic disease shows elevated ferritin (>100 μg/L), low transferrin saturation (<20%), and normal or low MCV 3, 2
• Thalassemia presents with normal or elevated ferritin and requires hemoglobin electrophoresis for confirmation 1, 2
• Sideroblastic anemia is identified by sideroblasts on bone marrow biopsy 3
• Lead poisoning should be considered as a rare cause 1

Normocytic Anemia (MCV 80-100 fL)

• Acute hemorrhage presents with positive stool guaiac or endoscopy findings 3
• Hemolysis shows positive Coombs test, low haptoglobin, elevated indirect bilirubin, and elevated LDH 3, 4
• Renal anemia occurs with glomerular filtration rate <60 mL/min/1.73 m² and low erythropoietin levels 3
• Bone marrow failure from cancer infiltration or myelosuppressive therapy 3, 1
• Anemia of chronic inflammation related to cancer, infection, or inflammatory diseases 3, 1

Macrocytic Anemia (MCV > 100 fL)

• Vitamin B12 deficiency confirmed by low serum B12 levels, typically megaloblastic 3, 1, 4
• Folate deficiency confirmed by low folate levels, also megaloblastic 3, 1, 4
• Myelodysplastic syndrome 1
• Medication-induced from hydroxyurea, diphenytoin, or other drugs 3, 1
• Alcoholism causes non-megaloblastic macrocytosis 3
• Hypothyroidism 1

Kinetic Classification by Reticulocyte Index

Low or Normal Reticulocyte Index (RI 1.0-2.0 or below)

This indicates decreased red blood cell production: 3

• Iron deficiency 3, 1
• Vitamin B12/folate deficiency 3, 1
• Aplastic anemia 3
• Bone marrow dysfunction from cancer or chemotherapy/radiation 3
• Anemia of chronic disease 1

High Reticulocyte Index (RI > 2.0)

This indicates normal or increased red blood cell production with ongoing loss or destruction: 3

• Acute blood loss 3, 1
• Hemolysis 3, 1
• Hemoglobinopathies like thalassemia (microcytic with high reticulocytes) 1

Essential Initial Laboratory Workup

Order these tests for every patient with suspected anemia: 1, 2, 4

• Complete blood count with differential and indices (hemoglobin, hematocrit, MCV, MCH, MCHC, RDW) 2, 4
• Reticulocyte count (corrected for degree of anemia to calculate reticulocyte index) 3, 2
• Peripheral blood smear for visual confirmation of RBC size, shape, and color 3
• Serum ferritin 1, 2, 4
• Transferrin saturation (calculated from serum iron and total iron binding capacity) 3, 1, 2
• C-reactive protein to assess for inflammation (alters interpretation of ferritin) 1, 2, 4

Combined Approach Algorithm

Use both MCV and reticulocyte index together for accurate diagnosis: 1, 2

Microcytic + Low/Normal Reticulocytes

• Iron deficiency, anemia of chronic disease, lead poisoning, hereditary anemias 1

Microcytic + High Reticulocytes

• Hemoglobinopathies such as thalassemia 1

Normocytic + Low/Normal Reticulocytes

• Acute hemorrhage (early), renal anemia, anemia of chronic disease, bone marrow failure 1

Normocytic + High Reticulocytes

• Acute blood loss, hemolysis 1

Macrocytic + Low/Normal Reticulocytes

• Vitamin B12 or folate deficiency, myelodysplastic syndrome, medication effects, hypothyroidism 1

Critical Diagnostic Pitfalls to Avoid

• Never rely solely on MCV because coexisting conditions (e.g., iron deficiency plus B12 deficiency) can neutralize MCV changes, producing falsely normal values despite significant disease 2
• Always measure C-reactive protein before interpreting ferritin, as inflammation elevates ferritin even in true iron deficiency; ferritin 30-100 μg/L with inflammation may still indicate iron deficiency 2, 4
• High RDW indicates mixed deficiencies or early iron deficiency even when MCV remains normal 2, 4
• Soluble transferrin receptor helps distinguish iron deficiency anemia from anemia of chronic disease when ferritin is equivocal 2
• Folic acid >0.1 mg daily masks B12 deficiency by correcting anemia while allowing irreversible neurologic damage to progress; always check B12 before treating with folate 5
• Failing to investigate underlying causes (gastrointestinal bleeding in iron deficiency, pernicious anemia in B12 deficiency) leads to inadequate treatment 2, 4
• Reticulocyte count must be corrected for the degree of anemia to calculate reticulocyte index; uncorrected values are misleading 3