What is the initial evaluation and treatment approach for anemia?

Initial Evaluation and Treatment of Anemia

Begin with a complete blood count (CBC) with indices and peripheral blood smear review, followed by reticulocyte index calculation and iron studies to systematically categorize the anemia and guide treatment. 1

Initial Laboratory Assessment

Order these tests immediately:

• CBC with differential to assess hemoglobin, MCV, and identify other cytopenias 1
• Peripheral blood smear to visually confirm RBC size, shape, and color—this is critical and non-negotiable 1
• Reticulocyte count with reticulocyte index (RI) to assess bone marrow response appropriateness 1
• Iron panel including serum iron, total iron-binding capacity (TIBC), transferrin saturation (TSAT), and ferritin 1

Key caveat: Hemoglobin is preferred over hematocrit because it has better reproducibility across laboratories and is not affected by storage time or serum glucose levels 1. If abnormalities exist in two or more cell lines (WBC, hemoglobin, platelets), consult hematology immediately as this suggests bone marrow dysfunction 1.

Morphologic Classification by MCV

Categorize based on mean corpuscular volume:

Microcytic Anemia (MCV < 80 fL)

• Most commonly iron deficiency; also consider thalassemia, anemia of chronic disease, or sideroblastic anemia 1
• Absolute iron deficiency: TSAT < 15% AND ferritin < 30 ng/mL 1
• Treatment: Iron supplementation should be initiated before considering any erythropoietin therapy 2

Normocytic Anemia (MCV 80-100 fL)

• Consider hemorrhage, hemolysis, bone marrow failure, chronic inflammation, or renal insufficiency 1
• The reticulocyte index is the key follow-up test here 1

Macrocytic Anemia (MCV > 100 fL)

• Most is megaloblastic: vitamin B12 or folate deficiency from insufficient uptake or lack of intrinsic factor 1
• Non-megaloblastic causes include alcoholism, MDS, hydroxyurea, or diphenytoin 1
• Treatment for B12 deficiency: 100 mcg IM daily for 6-7 days, then alternate days for seven doses, then every 3-4 days for 2-3 weeks, followed by 100 mcg monthly for life 3

Kinetic Classification by Reticulocyte Index

Normal RI ranges 1.0-2.0:

Low RI (< 1.0)

• Indicates decreased RBC production 1
• Suggests iron deficiency, vitamin B12/folate deficiency, aplastic anemia, or bone marrow dysfunction from cancer/chemotherapy 1
• In CKD patients with adequate iron, folate, and B12, the most common cause is insufficient erythropoietin production or inflammation 1

High RI (> 2.0)

• Indicates normal or increased RBC production despite anemia 1
• Suggests ongoing blood loss or hemolysis 1
• Look for signs of hemolysis: jaundice, splenic enlargement, elevated indirect bilirubin 1

Critical History and Physical Examination Findings

Obtain these specific details:

• Duration and onset of symptoms (acute vs. chronic) 1
• Symptoms: syncope, exercise dyspnea, headache, vertigo, chest pain, fatigue disrupting daily activities, abnormal menstruation 1
• Comorbidities: chronic kidney disease, cancer, inflammatory conditions 1
• Medications: chemotherapy, hydroxyurea, diphenytoin 1
• Physical signs of underlying causes: jaundice (hemolysis), splenic enlargement (hemolysis/malignancy), neurologic symptoms (B12 deficiency), blood in stool (GI bleeding), petechiae (thrombocytopenia), heart murmur (endocarditis/hemolysis) 1

Treatment Approach Based on Etiology

Iron Deficiency Anemia

• Iron supplementation is first-line before any erythropoietin therapy 2
• In non-dialysis CKD patients without menstrual losses, iron deficiency should prompt careful assessment for GI bleeding 1
• Goal: hemoglobin increase of at least 2 g/dL within 4 weeks 2

Vitamin B12 Deficiency

• Parenteral B12 is required for pernicious anemia (oral form is not dependable) 3
• Dosing: 100 mcg IM daily for 6-7 days, then alternate days for seven doses, then every 3-4 days for 2-3 weeks, then 100 mcg monthly for life 3
• Administer folic acid concomitantly if needed 3

Anemia of Chronic Disease/Inflammation

• Address the underlying inflammatory condition first 2
• If ferritin > 100 ng/mL but TSAT < 20% with elevated CRP, this indicates functional iron deficiency—iron supplementation is still recommended 2
• If iron repletion alone is insufficient after 1-3 months, erythropoietin-stimulating agents may be indicated 2

Common Pitfalls to Avoid

• Never rely on serum iron alone—always calculate TSAT and check ferritin 2
• Ferritin is an acute-phase reactant—it can be falsely elevated in inflammation, making interpretation difficult without TSAT 1
• Do not start erythropoietin therapy without adequate iron stores—iron demands exceed availability during erythropoietin treatment 2
• A hemoglobin drop of 2 g/dL or more from baseline warrants evaluation even if the absolute value is not below the standard threshold 1
• Avoid IV administration of vitamin B12—almost all will be lost in urine 3