Iron-Deficiency Anemia: A Comprehensive Clinical Review
Camaschella C • New England Journal of Medicine
Key Finding
Iron deficiency is the most common nutritional deficiency worldwide, affecting an estimated 2 billion people, with ferritin being the most sensitive early marker.
Key Findings
- 1Iron deficiency progresses through stages: depleted stores → iron-deficient erythropoiesis → anemia
- 2Ferritin drops before hemoglobin - making it the earliest indicator of deficiency
- 3Common causes include blood loss, inadequate intake, and malabsorption
- 4Oral iron remains first-line treatment; IV iron for malabsorption or intolerance
- 5Response to treatment: reticulocyte rise in 7-10 days, hemoglobin rise in 2-3 weeks
Original title: “Iron-Deficiency Anemia”
Plain English Summary
This authoritative NEJM review covers the pathophysiology, diagnosis, and treatment of iron-deficiency anemia. It emphasizes that iron deficiency is a spectrum - from depleted stores (low ferritin) to iron-deficient erythropoiesis to frank anemia. The review covers causes, diagnostic approaches, and treatment strategies including oral and IV iron.
In-Depth Analysis
This comprehensive NEJM review provides the definitive clinical framework for understanding iron-deficiency anemia.
Stages of Iron Deficiency
Stage 1: Depleted Iron Stores
- •Ferritin decreases (<30 ng/mL)
- •Hemoglobin still normal
- •Patient may be asymptomatic or have subtle symptoms
Stage 2: Iron-Deficient Erythropoiesis
- •Transferrin saturation decreases (<20%)
- •Serum iron low, TIBC elevated
- •Hemoglobin borderline or mildly low
- •Symptoms often present: fatigue, decreased exercise capacity
Stage 3: Iron-Deficiency Anemia
- •Hemoglobin below normal range
- •Microcytic, hypochromic red cells
- •Classic symptoms: pallor, fatigue, dyspnea on exertion
Diagnostic Approach
- •Ferritin - Most sensitive early marker (but rises with inflammation)
- •Transferrin saturation - <20% suggests iron deficiency
- •Soluble transferrin receptor - Elevated in deficiency, unaffected by inflammation
- •Reticulocyte hemoglobin - Early marker of functional iron deficiency
Treatment Response Timeline
- •Reticulocyte count rises: 7-10 days
- •Hemoglobin increases: 2-3 weeks
- •Full hemoglobin recovery: 6-8 weeks
- •Iron stores replete: 3-6 months
Paradigm Relevance
How this study applies to different clinical perspectives:
Standard Medical
RelevantConventional clinical guidelines used by most doctors
Research Consensus
RelevantCurrent scientific understanding, often ahead of guidelines
Metabolic Optimization
Proactive targets for optimal health, not just disease absence
Not directly relevant to this paradigm
Study Details
- Type
- Review Article
Related Biomarkers
Calculate & Evaluate on Metabolicum
Original Source
DOI (Digital Object Identifier) is a permanent link to this publication. Unlike website URLs that can change, a DOI always resolves to the correct source.
Related Studies
The effect of low versus high fractional iron absorption on iron absorption and utilization
Stoffel NU, et al • American Journal of Clinical Nutrition • 2020
Alternate-day iron absorption 40-50% higher than consecutive day (p<0.001); 200mg alternate-day yields ~2x total absorption vs 100mg consecutive-day
Every-Other-Day Iron Supplementation Is More Effective Than Daily Dosing
Stoffel NU, et al • American Journal of Clinical Nutrition • 2017
Alternate-day iron dosing results in 34% higher fractional absorption compared to daily dosing, due to hepcidin dynamics.
Iron Status of Vegetarian Adults: A Review of Literature
Pawlak R, et al • American Journal of Lifestyle Medicine • 2016
Female vegetarians: ferritin <12 µg/L prevalence 12-79%; inadequate hemoglobin 6-30.3%. Male vegetarians: ferritin <12 µg/L prevalence 1.7-29%