What is the initial step in anemia workup and subsequent treatment?

Initial Anemia Workup and Treatment Algorithm

The initial step in anemia workup should be a complete blood count (CBC) with indices, reticulocyte count, serum ferritin, transferrin saturation, and CRP concentration when hemoglobin falls below normal levels (< 12 g/dL for women and < 13 g/dL for men). 1

Diagnostic Approach

Step 1: Confirm Anemia

• Anemia is defined according to WHO criteria: hemoglobin < 12 g/dL in non-pregnant women, < 11 g/dL in pregnant women, and < 13 g/dL in men 1
• Regular monitoring is recommended, especially in high-risk patients (e.g., those with chronic diseases, IBD, or CKD) 1

Step 2: Initial Laboratory Evaluation

• Minimum workup includes:
  • Complete blood count with red cell indices (MCV, RDW) 1
  • Reticulocyte count 1
  • Differential blood cell count 1
  • Serum ferritin 1
  • Transferrin saturation (TfS) 1
  • C-reactive protein (CRP) 1

Step 3: Classification Based on MCV

• Microcytic (MCV < 80 fL):

  • Most commonly indicates iron deficiency anemia 1, 2
  • Other causes: thalassemia, anemia of chronic disease, sideroblastic anemia 1, 2
  • Key follow-up tests: serum ferritin, iron, TIBC, transferrin saturation 3, 4

• Normocytic (MCV 80-100 fL):

  • May indicate hemorrhage, hemolysis, bone marrow failure, anemia of chronic inflammation, or renal insufficiency 1
  • Key follow-up test: reticulocyte count 1, 5

• Macrocytic (MCV > 100 fL):

  • May indicate vitamin B12 or folate deficiency 1
  • Other causes: medications (e.g., azathioprine), alcohol abuse, hypothyroidism, reticulocytosis 1

Step 4: Interpret Reticulocyte Count

• Low or normal reticulocytes: indicates impaired erythropoiesis (deficiencies, bone marrow disease) 1
• Elevated reticulocytes: indicates increased red cell production, suggesting hemolysis rather than deficiency 1

Step 5: Further Diagnostic Testing Based on Initial Results

• For suspected iron deficiency:

  • Diagnostic criteria depend on inflammation status 1
  • Without inflammation: serum ferritin < 30 μg/L confirms iron deficiency 1
  • With inflammation: serum ferritin up to 100 μg/L may still indicate iron deficiency 1

• For suspected vitamin deficiencies:

  • Measure vitamin B12 and folate levels 1
  • Consider methylmalonic acid and homocysteine for B12 deficiency confirmation 6

• For suspected hemolysis:

  • Measure haptoglobin, LDH, and bilirubin 1

Treatment Approach

Iron Deficiency Anemia

• Oral iron supplementation is first-line therapy for most patients 3
• Investigate underlying cause, particularly gastrointestinal blood loss in adults 4
• Consider IV iron for patients with malabsorption, severe anemia, or intolerance to oral preparations 3

Vitamin B12 Deficiency

• Parenteral vitamin B12 (100 mcg daily for 6-7 days) for pernicious anemia or severe deficiency 6
• Maintenance: 100 mcg monthly for life in pernicious anemia 6
• Oral supplementation for patients with normal intestinal absorption 6

Folate Deficiency

• Oral folate supplementation 1
• Caution: High-dose folic acid may mask B12 deficiency symptoms while allowing neurological damage to progress 6

Anemia of Chronic Disease

• Treat underlying condition 1
• Consider erythropoietin therapy in specific situations (e.g., CKD) 1

Common Pitfalls and Caveats

• Relying solely on MCV for diagnosis: MCV-guided classification may lead to incorrect exclusion of certain etiologies; a broader set of laboratory tests is recommended 7
• Missing mixed anemias: Microcytosis and macrocytosis can coexist, neutralizing each other and resulting in normal MCV; high RDW can help identify this situation 1
• Overlooking inflammation: Inflammatory states alter iron parameters; ferritin (an acute phase reactant) may be normal or elevated despite iron deficiency 1
• Delaying B12 deficiency treatment: Vitamin B12 deficiency left untreated for over 3 months may cause permanent spinal cord damage 6
• Missing underlying malignancy: Iron deficiency anemia in adults warrants investigation for gastrointestinal malignancy 4