What are the initial lab tests for anemia workup?

Initial Laboratory Testing for Anemia Workup

Begin with a complete blood count (CBC) with red cell indices, reticulocyte count, and peripheral blood smear examination as your essential first-line tests. 1, 2, 3

Core Initial Tests

Mandatory First-Line Panel

• CBC with differential and indices including hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW), white blood cells, and platelets 1, 2
• Reticulocyte count (corrected for degree of anemia as reticulocyte index) to assess bone marrow production capacity and distinguish between decreased RBC production versus increased destruction or loss 1, 3
• Peripheral blood smear with visual review to confirm RBC size, shape, color, and identify morphologic abnormalities 1, 2

Essential Iron Studies

• Serum ferritin as the single most useful marker for tissue iron stores 1, 2, 3
• Transferrin saturation (calculated from serum iron and total iron-binding capacity) to assess iron available for erythropoiesis 1, 2
• Total iron-binding capacity (TIBC) 1, 2

Additional Initial Tests

• C-reactive protein (CRP) to assess for inflammation, which affects ferritin interpretation 1, 2

Algorithmic Approach Based on MCV

Microcytic Anemia (MCV < 80 fL)

• Iron deficiency is confirmed when ferritin < 30 ng/mL and transferrin saturation < 15% 1, 2, 3
• If iron studies are normal, consider thalassemia (obtain hemoglobin electrophoresis), anemia of chronic disease, or sideroblastic anemia 1, 2, 3
• Search for blood loss source with stool guaiac testing for occult gastrointestinal bleeding when iron deficiency is identified 1, 2

Normocytic Anemia (MCV 80-100 fL)

• Reticulocyte index is the key discriminator 1, 3
• Low reticulocyte index (< 2.0) indicates decreased RBC production from iron deficiency, vitamin B12/folate deficiency, aplastic anemia, bone marrow dysfunction, or chronic kidney disease 1
• High reticulocyte index (> 2.0) indicates appropriate bone marrow response, suggesting hemorrhage or hemolysis 1, 3
• For suspected hemolysis, add haptoglobin, lactate dehydrogenase (LDH), and bilirubin 2, 3

Macrocytic Anemia (MCV > 100 fL)

• Measure vitamin B12 and folate levels to identify megaloblastic causes 1, 2, 3
• Consider non-megaloblastic causes including alcoholism, myelodysplastic syndrome, hypothyroidism, or drug effects (hydroxyurea, diphenytoin) 1

Critical Interpretation Points

Ferritin Interpretation Requires Clinical Context

• Ferritin is an acute-phase reactant and can be falsely elevated with inflammation, chronic disease, malignancy, or liver disease 1, 2
• In chronic kidney disease patients on hemodialysis, ferritin interpretation is particularly difficult due to inflammatory elevation 1
• When inflammation is present (elevated CRP), higher ferritin thresholds may be needed to exclude iron deficiency 1, 2

Reticulocyte Count Significance

• Normal reticulocyte index ranges 1.0-2.0 1
• Low count with anemia indicates inadequate bone marrow response from iron/folate/B12 deficiency, insufficient erythropoietin, or inflammation 1
• Must be corrected for degree of anemia (reticulocyte index) rather than using absolute count 1

Multiple Cell Line Abnormalities

• Abnormalities in two or more cell lines (RBCs, WBCs, platelets) warrant hematology consultation, as this suggests bone marrow dysfunction rather than isolated anemia 1

Common Pitfalls to Avoid

• Never rely on hemoglobin/hematocrit alone without iron studies, as normal CBC parameters can coexist with iron depletion, and individuals may be misdiagnosed as normal when they have early iron deficiency 4
• Do not measure serum erythropoietin levels in chronic kidney disease patients with normochromic, normocytic anemia, as it is rarely elevated and does not change management 1, 3
• Watch for combined deficiencies, particularly in elderly patients and those with inflammatory bowel disease, where multiple nutritional deficiencies may coexist 3
• Ferritin < 25 ng/mL in males and < 11 ng/mL in females predicts insufficient iron stores in non-dialysis chronic kidney disease patients 1
• High-dose folic acid supplementation may mask vitamin B12 deficiency symptoms, so always check B12 before treating macrocytic anemia with folate alone 2, 3