What is the appropriate work‑up for an asymptomatic teenage female with low hemoglobin?

Work-Up for Low Hemoglobin in an Asymptomatic Teenage Female

Begin with a complete blood count including red cell indices (MCV, RDW) and reticulocyte count, plus serum ferritin and transferrin saturation—this minimum panel will identify iron deficiency anemia in the vast majority of cases. 1

Initial Laboratory Assessment

The first-line work-up should include:

• Complete blood count with red cell indices: Obtain hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and red cell distribution width (RDW) 1
• Reticulocyte count: Distinguishes between inadequate red cell production versus increased destruction or loss 1
• Serum ferritin: The most specific marker for iron stores; levels <15 μg/L confirm iron deficiency 1, 2
• Transferrin saturation (TSAT): Values <20% indicate iron-restricted erythropoiesis 1
• C-reactive protein (CRP): Identifies inflammation that may elevate ferritin and mask iron deficiency 1

Interpreting the Results

Step 1: Classify by MCV

Microcytic anemia (MCV <80 fL):

• Iron deficiency is the most common cause in adolescent females, accounting for 49-64% of cases with low MCV 1, 3
• Ferritin <15 μg/L confirms iron deficiency 1, 2
• If ferritin is normal or elevated, consider thalassemia trait (especially in patients of African, Mediterranean, or Southeast Asian ancestry) or chronic disease 1, 2
• Thalassemia trait typically shows low MCV with normal RDW (≤14%), whereas iron deficiency shows elevated RDW (>14%) 1, 2

Normocytic anemia (MCV 80-100 fL):

• Check reticulocyte count, creatinine, and CRP 1
• Low/normal reticulocytes suggest chronic disease, renal insufficiency, or early iron deficiency 1
• Elevated reticulocytes indicate hemolysis or blood loss—proceed to haptoglobin, lactate dehydrogenase, and bilirubin 1

Macrocytic anemia (MCV >100 fL):

• Obtain vitamin B12 and folate levels 1
• Consider thyroid function tests (TSH) to exclude hypothyroidism 1

Step 2: Assess Reticulocyte Response

• Low or "normal" reticulocytes with anemia indicate impaired red cell production due to nutritional deficiencies, bone marrow disease, or chronic inflammation 1
• Elevated reticulocytes suggest hemolysis or acute blood loss—measure haptoglobin, lactate dehydrogenase, and indirect bilirubin 1

Risk Factors Requiring Attention

Adolescent females at highest risk for iron deficiency include those with:

• Heavy menstrual bleeding (the leading cause in this population) 1
• Restrictive diets: vegetarian, vegan, or avoidance of red meat 1
• High-impact or endurance sports with repetitive ground strikes 1
• Previous iron deficiency anemia 1

Extended Work-Up (When Initial Tests Are Inconclusive)

If the diagnosis remains unclear after the minimum panel:

• Vitamin B12 and folic acid levels to exclude megaloblastic anemia 1
• Haptoglobin and lactate dehydrogenase if hemolysis is suspected 1
• Differential white blood cell count to assess for infection or hematologic disorders 1
• Hemoglobin electrophoresis if thalassemia or hemoglobinopathy is suspected (particularly in patients of African, Mediterranean, or Southeast Asian descent with microcytosis unresponsive to iron) 1, 2
• Hematology consultation if the cause remains unclear after extended testing 1

Common Pitfalls to Avoid

• Do not rely on hemoglobin and hematocrit alone—these decrease only with severe iron depletion and can miss early deficiency 4
• Ferritin is an acute-phase reactant: values may be falsely elevated during illness or inflammation, masking iron deficiency 1
• In the presence of inflammation (elevated CRP), ferritin up to 100 μg/L may still indicate iron deficiency 1
• A normal MCV does not exclude iron deficiency—coexisting microcytosis and macrocytosis can neutralize each other; an elevated RDW suggests mixed deficiencies 1
• Microcytic anemia in a patient with known thalassemia trait should not be automatically attributed to the hemoglobinopathy—concurrent iron deficiency must be actively excluded 2

Therapeutic Trial as Diagnostic Confirmation

For adolescent females with presumptive iron deficiency anemia:

• Prescribe 60-120 mg elemental iron daily between meals 1, 2
• Recheck hemoglobin after 4 weeks: an increase ≥1 g/dL (or hematocrit ≥3%) confirms the diagnosis 1, 2
• If confirmed, continue iron for 2-3 additional months to replenish stores, then reassess hemoglobin approximately 6 months after completion 1, 2
• If no response after 4 weeks despite compliance, obtain MCV, RDW, and ferritin to reassess—ferritin ≥15 μg/L suggests an alternative etiology 1, 2