What is the likely cause of microcytosis with hypoferritinemia (low iron) and low iron saturation in a 30-year-old obese female?

Microcytosis with Low Iron Saturation in a 30-Year-Old Obese Female

This presentation is most consistent with iron deficiency anemia (IDA), as the combination of microcytosis, low total iron (87), and low transferrin saturation (29%) indicates depleted iron stores despite what may appear to be "normal" ferritin levels. 1

Diagnostic Interpretation

The 29% transferrin saturation is the key finding here. While you haven't provided the ferritin level, the low iron saturation strongly suggests iron deficiency:

• Transferrin saturation <30% supports iron deficiency even when ferritin appears normal 2
• In the absence of inflammation, serum ferritin <30 μg/L confirms iron deficiency, but ferritin up to 45 μg/L may still represent iron deficiency with optimal sensitivity-specificity trade-off 1
• If ferritin is between 30-100 μg/L with inflammation present, iron deficiency remains likely 1

Primary Differential Diagnoses

1. Iron Deficiency Anemia (Most Likely)

• Low serum iron (87) combined with low transferrin saturation (29%) is diagnostic 1, 3
• In a 30-year-old female, common causes include:
  • Menstrual blood loss (most common in premenopausal women) 1, 3
  • Gastrointestinal blood loss (must be excluded, especially with obesity-related GERD or NSAID use) 1, 3
  • Malabsorption (celiac disease found in 3-5% of IDA cases) 1
  • Dietary insufficiency (less common but possible) 1

2. Anemia of Chronic Disease (Less Likely)

• Would typically show low iron BUT also low total iron-binding capacity and transferrin saturation <20% 1
• Your patient's 29% saturation makes this less likely 1
• Obesity can be associated with chronic inflammation, which could complicate interpretation 1

3. Beta-Thalassemia Trait (Consider if Iron Studies Remain Equivocal)

• Presents with microcytosis disproportionate to degree of anemia 1, 3
• Normal or elevated RDW favors thalassemia over iron deficiency 2, 3
• Requires hemoglobin electrophoresis showing HbA2 >3.5% for diagnosis 4, 3

Recommended Diagnostic Workup

Complete the iron panel immediately:

• Serum ferritin (if not already done—this is the single most useful marker) 1
• Total iron-binding capacity (TIBC) (should be elevated in iron deficiency) 3, 5
• Red cell distribution width (RDW) (elevated >14% suggests iron deficiency) 2

If ferritin <45 μg/L with low transferrin saturation, diagnose iron deficiency and investigate the source:

• Screen for celiac disease with tissue transglutaminase antibodies 1
• Assess menstrual history (quantity, duration, frequency) 1
• Urinalysis to exclude hematuria 1
• Consider upper and lower GI endoscopy if no obvious source, especially with GI symptoms, family history of GI malignancy, or inadequate response to iron therapy 1

If ferritin is normal (>45 μg/L) but transferrin saturation remains low:

• Consider functional iron deficiency in the context of obesity-related inflammation 1, 2
• Order hemoglobin electrophoresis to exclude thalassemia trait 1, 2

Critical Clinical Pitfalls

Ferritin is an acute phase reactant—obesity-related chronic inflammation can falsely elevate ferritin, masking true iron deficiency 1, 2. A ferritin of 30-100 μg/L does NOT exclude iron deficiency in this context 1.

Do not assume menstrual blood loss is the sole cause without investigation—while common in premenopausal women, GI pathology (including malignancy) must be excluded if there are any red flags: GI symptoms, family history, or failure to respond to iron supplementation 1.

A therapeutic trial of iron can be diagnostic—a hemoglobin rise ≥10 g/L within 2 weeks strongly confirms iron deficiency, even if iron studies are equivocal 1.