What is the work-up for microcytic anemia with a low hemoglobin level?

Work-up for Microcytic Anemia (MCV 63.8 fL, Hemoglobin 9.8 g/dL)

This patient requires immediate iron studies (serum ferritin, transferrin saturation, serum iron, and TIBC) as the first-line diagnostic step, followed by additional testing based on those results to differentiate between iron deficiency anemia, thalassemia trait, anemia of chronic disease, and other causes of microcytosis. 1

Initial Laboratory Work-up

The minimum essential tests for microcytic anemia include: 1

• Complete blood count with red cell indices (already obtained - shows MCV 63.8, MCH 20.3, MCHC 318, RDW-CV 0.178)
• Reticulocyte count - to assess bone marrow response and differentiate hypoproliferative from hemolytic causes 1
• Serum ferritin - most definitive single test for iron deficiency 1, 2, 3
• Transferrin saturation (TSAT) - reflects immediately available iron for hemoglobin synthesis 1
• Serum iron and total iron binding capacity (TIBC) 1
• C-reactive protein (CRP) - to assess for inflammation that may affect ferritin interpretation 1

Interpretation Algorithm Based on Iron Studies

If Ferritin <30 μg/L (without inflammation) or <100 μg/L (with inflammation):

This indicates iron deficiency anemia, the most common cause of microcytic anemia. 1, 2

Additional work-up required to identify the source: 1

• Stool guaiac test for occult gastrointestinal bleeding 1
• Dietary history - assess iron intake 1
• Menstrual history in premenopausal women - assess blood loss 1, 2
• Gastrointestinal evaluation (upper and lower endoscopy) if no obvious source identified, particularly in men and postmenopausal women 1
• Celiac disease screening (tissue transglutaminase antibodies) - can cause malabsorption 1
• Helicobacter pylori testing - associated with iron deficiency 1

If Ferritin Normal or Elevated with Low TSAT (<16-20%):

This suggests functional iron deficiency or anemia of chronic disease. 1

Additional testing: 1

• Creatinine and BUN - assess for chronic kidney disease 1
• Inflammatory markers - ESR, CRP if not already done 1
• Consider soluble transferrin receptor or reticulocyte hemoglobin equivalent to confirm functional iron deficiency 1

If Ferritin Normal/High with Normal/High TSAT and Markedly Low MCV (as in this case with MCV 63.8):

This pattern strongly suggests thalassemia trait, particularly with: 1, 4

• MCV disproportionately low relative to degree of anemia
• RDW normal or only mildly elevated (this patient's RDW-CV 0.178 is elevated, making thalassemia less likely but not excluded)
• Normal or elevated red blood cell count

Required testing: 1

• Hemoglobin electrophoresis - diagnostic for beta-thalassemia (HbA2 >3.5%) and identifies hemoglobinopathies 1
• Iron studies to exclude concurrent iron deficiency - thalassemia and iron deficiency can coexist 1, 4

Extended Work-up if Initial Tests Inconclusive

If the cause remains unclear after initial evaluation: 1

• Vitamin B12 and folate levels - can cause macrocytosis but occasionally mixed pictures 1
• Thyroid function tests (TSH) - hypothyroidism can contribute to anemia 1
• Lead level - if occupational or environmental exposure suspected 1
• Zinc protoporphyrin or percentage of hypochromic red cells - alternative markers of iron-restricted erythropoiesis 1
• Haptoglobin, lactate dehydrogenase, and bilirubin - if reticulocyte count elevated, to assess for hemolysis 1
• Bone marrow examination - reserved for cases where diagnosis remains uncertain after comprehensive testing, to assess iron stores directly and evaluate for sideroblastic anemia or other bone marrow disorders 1, 2

Critical Pitfalls to Avoid

• Do not rely on ferritin alone in the presence of inflammation - ferritin is an acute phase reactant and can be falsely elevated; use TSAT <20% as additional criterion for iron deficiency when ferritin is 30-100 μg/L 1
• Do not miss thalassemia trait - the extremely low MCV (63.8) relative to mild anemia suggests this diagnosis; inappropriate iron therapy in thalassemia can cause iron overload 1, 4
• Do not start iron therapy before obtaining iron studies - this will confound subsequent diagnostic evaluation 1, 2
• Do not overlook gastrointestinal malignancy - iron deficiency in men and postmenopausal women mandates GI evaluation even without obvious bleeding 1