Data-driven physiologic thresholds for iron deficiency associated with hematologic decline.

Area of Science:

• Biochemistry
• Hematology
• Clinical Diagnostics

Background:

• Iron deficiency anemia is a global health issue, with current iron status tests lacking optimized reference intervals for diagnosis.
• Serum ferritin (SF) is a key indicator of iron status, but its interpretation for anemia diagnosis requires refinement.

Purpose of the Study:

• To identify optimal serum ferritin (SF) thresholds for diagnosing iron deficiency and assessing treatment response in anemia.
• To establish age- and sex-specific SF thresholds to improve diagnostic accuracy.

Main Methods:

• Analysis of paired red blood cell and SF measurements from two large adult cohorts at Massachusetts General Hospital.
• Utilizing inter-patient data to define SF thresholds for hematologic decline and intra-patient data to identify SF thresholds for hematologic improvement.

Main Results:

• Optimal SF thresholds associated with a ~5% decline in red cell index ranged from 10-25 ng/mL, varying by age and sex.
• Thresholds for younger women were lower than for older women and men, both for diagnosing decline and predicting improvement.
• Specific thresholds identified: ~10-25 ng/mL for decline, ~15 ng/mL (younger women), ~25 ng/mL (older women), and ~35 ng/mL (men) for improvement.

Conclusions:

• Current SF reference intervals are suboptimal for anemia diagnosis.
• Implementing age- and sex-specific SF thresholds can enhance diagnostic accuracy for iron deficiency and treatment monitoring.
• Clinical databases offer valuable physiologic evidence for refining diagnostic test thresholds.