What are the causes and treatments of low iron saturation?

Causes and Treatment of Low Iron Saturation

Low iron saturation (transferrin saturation <16%) indicates iron deficiency and requires appropriate investigation and treatment based on underlying causes.

Causes of Low Iron Saturation

Blood Loss

• Gastrointestinal bleeding (including from colorectal cancer, gastric cancer, peptic ulcers, inflammatory bowel disease, angiodysplasia) 1
• Menstrual blood loss in women of reproductive age 1, 2
• Chronic nosebleeds 1
• Blood donation 1
• NSAID-induced GI bleeding 1

Reduced Iron Intake or Absorption

• Poor dietary iron intake, particularly in developing countries 2, 3
• Malabsorption due to:
  • Celiac disease 1, 2
  • Inflammatory bowel disease 2, 4
  • Gastrointestinal surgery (partial/total gastrectomy, gut resection or bypass) 1, 2
  • Long-term proton pump inhibitor therapy (causing hypochlorhydria) 1
  • Atrophic gastritis 2
  • Bariatric surgical procedures 2

Increased Iron Requirements

• Pregnancy (especially third trimester) 2, 5
• Endurance athletes (possibly due to high hepcidin levels) 1
• Periods of rapid growth (infancy, adolescence) 1, 5

Chronic Inflammatory Conditions

• Anemia of chronic disease/inflammation 1
• Chronic kidney disease 1, 2
• Heart failure 2
• Cancer 2, 4

Diagnosis of Low Iron Saturation

Laboratory Assessment

• Transferrin saturation <16% indicates iron deficiency 1
• Serum ferritin assessment is crucial:
  • <30 μg/L indicates absolute iron deficiency in the absence of inflammation 1
  • 30-100 μg/L with transferrin saturation <16% suggests combined iron deficiency and anemia of chronic disease 1

  • 100 μg/L with transferrin saturation <16% suggests anemia of chronic disease 1

• Inflammatory markers (CRP, ESR) should be measured to aid interpretation of ferritin levels 1
• Complete blood count to assess for anemia and microcytosis 1

Clinical Evaluation

• Assess for symptoms of iron deficiency: fatigue, breathlessness, angular stomatitis, glossitis, koilonychia, restless legs syndrome, pagophagia (ice craving), blue sclerae 1, 2
• Evaluate for GI symptoms and blood loss 1
• Screen for risk factors: menstruation, pregnancy, blood donation, NSAID use, previous GI surgery 1
• Consider urinalysis to exclude microscopic hematuria which may indicate renal pathology 1

Treatment Approach

Identify and Treat Underlying Cause

• Gastrointestinal investigation (gastroscopy and colonoscopy) is recommended for men and postmenopausal women with iron deficiency anemia 1
• Celiac disease screening should be performed in all patients with unexplained iron deficiency 1
• Address any sources of blood loss 1
• Discontinue medications that may contribute to iron deficiency (NSAIDs, PPIs if possible) 1, 6

Iron Replacement Therapy

• Oral iron supplementation is first-line therapy for most patients 2, 7:

  • Ferrous sulfate 325 mg (65 mg elemental iron) daily or on alternate days 6, 2
  • Take between meals to maximize absorption 6, 7
  • Do not take within 2 hours of tetracycline antibiotics 6
  • May cause gastrointestinal side effects (nausea, constipation, diarrhea) 6, 7
  • Consider vitamin C co-ingestion to enhance non-heme iron absorption 1
  • Avoid tea and coffee around meal times as they impair iron absorption 1

• Intravenous iron is indicated for 2, 4:

  • Oral iron intolerance
  • Poor absorption (celiac disease, post-bariatric surgery)
  • Chronic inflammatory conditions (CKD, heart failure, IBD, cancer)
  • Ongoing blood loss
  • Second and third trimesters of pregnancy when needed

Dietary Recommendations

• Increase consumption of iron-rich foods 1, 3:
  • Heme iron sources (meat, seafood) have better bioavailability
  • Non-heme iron sources (green leafy vegetables, nuts, soya beans)
• In developing countries, iron-fortified staple foods may be necessary 3
• Recommended daily intake: 8-8.7 mg for males, 14.8-18 mg for females 1

Monitoring Response to Treatment

• Repeat hemoglobin measurement after 4 weeks of iron therapy 1
• An increase in hemoglobin ≥1 g/dL confirms iron deficiency anemia 1
• Continue iron treatment for 2-3 months after hemoglobin normalizes to replenish iron stores 1, 2
• Reassess hemoglobin approximately 6 months after successful treatment 1

Special Considerations

• In inflammatory conditions, standard ferritin cutoffs may miss iron deficiency; use higher threshold (100 μg/L) 1
• Soluble transferrin receptor measurement can help distinguish between iron deficiency and anemia of chronic disease 1
• Reticulocyte hemoglobin concentration may be a more accurate indicator of iron status during inflammation 1
• Consider parenteral iron in cases of pathologically impaired iron absorption 1