Most laboratory ferritin reference intervals result in under-diagnosis and under-treatment of iron deficiency, especially in women, Canadian researchers have concluded.
Current evidence shows that a serum ferritin concentration of less than 30 μg/L has a high specificity and sensitivity for diagnosing iron deficiency in adults.
But serum ferritin reference ranges for healthy adults reported in the published literature and used by laboratories in the real world usually have a lower limit of normal (LLN) below 30 μg/L, particularly for females, the researchers found.
In fact, the meta-analysis, which included 21,882 women and 23,650 men, revealed that the mean ferritin LLN reported in the literature was 9 μg/L for women and 25 μg/L for men.
Dr Sue Pavord, Haematology Consultant at Oxford University Hospitals, told the limbic: “There are still many laboratories that use very low ferritin values to define the lower limit of normal, without consideration that the population used to define this range includes iron deficient individuals, it being so highly prevalent in the population.”
The meta-analysis, published in The Lancet Haematology, showed that the five most commonly used commercial assays reported ferritin reference intervals with a mean LLN of 9 μg/L for women and 23 μg/L for men, thus employing lower cutoffs for women, which “structurally permits” their under-treatment, according to the paper.
“This practice is extremely concerning given the absence of physiological basis to support lower iron requirements in women and iron deficiency’s association with morbidity and mortality—whether anaemic or non-anaemic,” the authors said.
“Non-anaemic iron deficiency and iron deficiency anaemia are distinct conditions that are both prevalent and treatable, and therefore, their accurate diagnosis is essential,” they stressed.
In addition, the analysis showed that only the ferritin assay from Vitros provided ferritin reference intervals for females partitioned by age (6–137 μg/L for females younger than 50 years and 11–264 μg/L for those aged 50 years and older).
‘We know they are wrong’
Taking to X (formerly Twitter) to comment on so-called “normal” ranges of ferritin, Professor Michael Makris, Emeritus Professor of Haemostasis and Thrombosis at the University of Sheffield, said: “It is amazing that in 2024 we are still using these in young women when we know they are wrong. They fail to identify many iron deficient women.”
Excellent article in @TheLancetHaem about “normal” ranges of ferritin. It is amazing that in 2024 we are still using these in young women when we know they are wrong. They fail to identify many iron deficient women. Why are mainstream journalists not picking up the story, when it… pic.twitter.com/UwzeU1ON07
— Michael Makris (@ProfMakris) July 3, 2024
Urgent need for evidence-based limits
Some key limitations of the research included its limitation to studies published in England and the heterogeneity of its sample size and population type.
However, the findings show that “the published literature on ferritin reference interval supports an LLN substantially lower than 30 μg/L, despite robust evidence suggesting a ferritin concentration of less than 30 μg/L is in keeping with clinical iron deficiency,” the authors said.
“The use of current laboratory ferritin reference intervals will result in under-diagnosis and under-treatment of iron deficiency.
“Based on these findings, we suggest the urgent adoption of evidence-based ferritin clinical decision limits to help clinicians detect and treat iron deficiency to minimise propagation of related health inequity and social injustice in medicine,” they stressed.