Causes of Microcytosis in a Fit and Well 18-Year-Old Male
In a healthy 18-year-old male with microcytosis, iron deficiency is the most likely cause, followed by thalassemia trait, and these two conditions account for the vast majority of cases in this demographic. 1, 2
Primary Differential Diagnosis
The diagnostic approach should focus on distinguishing between the most common causes:
Iron Deficiency
- Iron deficiency is the single most common cause of microcytosis, even in apparently healthy young adults 1, 2, 3
- In young males, consider dietary insufficiency (vegetarian diet, poor nutrition), occult gastrointestinal blood loss (including NSAID use), or malabsorption 1, 2
- The red cell distribution width (RDW) is typically elevated (>14.0%) in iron deficiency, helping distinguish it from thalassemia 1
Thalassemia Trait
- Thalassemia trait should be strongly considered when the MCV is very low (often <70 fL) with a normal or elevated red blood cell count 1, 2
- Unlike iron deficiency, thalassemia trait presents with RDW ≤14.0% 1
- This is particularly important in patients of Mediterranean, African, Middle Eastern, or Southeast Asian ancestry 3, 4
Diagnostic Algorithm
Start with serum ferritin as the single most powerful initial test:
If Ferritin <12 μg/dL
- This is diagnostic of iron deficiency 1, 5
- Investigate the underlying cause: dietary history, NSAID use, and consider occult gastrointestinal blood loss 1, 2
If Ferritin is Normal (12-100 μg/dL)
- Check transferrin saturation: <30% supports iron deficiency 1, 5
- Consider hemoglobin electrophoresis to evaluate for thalassemia trait 6, 2
- Elevated hemoglobin A2 >3.5% is diagnostic for beta-thalassemia trait 7, 2
If Ferritin >100 μg/dL
- Iron deficiency is almost certainly excluded 5
- Proceed directly to hemoglobin electrophoresis for thalassemia evaluation 6, 2
Less Common Causes to Consider
While rare in a "fit and well" 18-year-old, these should be considered if initial workup is unrevealing:
Anemia of Chronic Disease
- Unlikely in a truly healthy individual, but can present with microcytosis 1, 2
- Characterized by low serum iron, low total iron-binding capacity, and normal-to-elevated ferritin 8, 2
- Consider if there are subtle signs of chronic inflammation, infection, or undiagnosed chronic conditions 1
Genetic Disorders of Iron Metabolism
- Iron-refractory iron-deficiency anemia (IRIDA) presents in childhood with remarkably low transferrin saturation, low-to-normal ferritin, and failure to respond to oral iron 1
- DMT1 deficiency causes microcytic anemia with paradoxically increased transferrin saturation 1
- These are rare but should be considered if there is failure to respond to appropriate iron therapy 8, 1
Sideroblastic Anemia
- Presents with elevated ferritin and transferrin saturation even before transfusions 1, 5
- Bone marrow examination showing ring sideroblasts is pathognomonic 8, 5
- Consider if ferritin and iron studies are paradoxically elevated 1
Critical Pitfalls to Avoid
- Do not assume dietary insufficiency or ethnic background explains microcytosis without laboratory confirmation—thalassemia must be confirmed by testing, not presumed based on ethnicity 5
- Do not overlook the possibility of combined iron deficiency and thalassemia trait, which can occur together and complicate the clinical picture 1
- Ferritin is an acute phase reactant and can be falsely elevated in the presence of inflammation, infection, or liver disease, potentially masking concurrent iron deficiency 5
- In a truly asymptomatic young male, gastrointestinal malignancy is unlikely but occult bleeding from other sources (including athletic-induced gastrointestinal blood loss or NSAID use) should still be considered 1, 2
Confirmatory Testing When Doubt Remains
- A therapeutic trial of oral iron (100 mg elemental iron twice daily) for 3 weeks is definitive: expect hemoglobin rise ≥10 g/L within 2 weeks if iron deficiency is present 5, 7
- Bone marrow aspiration showing absent iron stores remains the gold standard but is rarely necessary in straightforward cases 2, 9