Ferritin as a functional biomarker of iron status in children and young adults

Markus, C.; Saxon, Ben; Metz, Michael

doi:10.1111/bjh.15127

Cited by 13 publications

(29 citation statements)

References 2 publications

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“…An interesting study using non-linear quantile regression to correlate ferritin levels to hematological parameters was recently reported [20]. For children 4 months to <13 years of age, a lower limit of 30 mg/L was recommended.…”

Section: Discussionmentioning

confidence: 99%

When age really matters; ferritin reference intervals during infancy revisited

Larsson

Hillarp

Hellström‐Westas

et al. 2019

Scandinavian Journal of Clinical and Laboratory Investigation

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Infants are at risk for iron deficiency. Despite research advances, assessing iron stores during infancy remains a challenge to the clinician. Ferritin is the first-choice laboratory marker for measuring iron stores but it is today still unclear how to evaluate reference intervals among infants. We have studied Swedish infants (n ¼ 456), born at term after normal pregnancies. Ferritin was measured at birth (umbilical cord sample), 48-72 h, 4 months and 12 months. Lower and upper reference interval limits were constructed as the 2.5th and 97.5th percentiles. By a large study population, we were able to use more stringent measures to avoid interference from the acute phase response than previous reports on ferritin reference intervals. When we used mathematical transformation we furthermore avoided potential information loss in precision and confirmed earlier reports of sex differences. At the lower reference interval limits there were small differences between sexes. For the higher limits, the differences were more pronounced in the older infant. At 0-3 d of age we observed a difference between the sexes of only 5% at the upper limits. The differences peaked at 12 months, where the boys' upper 97.5th percentile was 56% compared to girls.

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Section: Discussionmentioning

confidence: 99%

When age really matters; ferritin reference intervals during infancy revisited

Larsson

Hillarp

Hellström‐Westas

et al. 2019

Scandinavian Journal of Clinical and Laboratory Investigation

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“…Specifically, that is for determining when iron levels are low enough to affect a patient's hematologic status or for deciding which patients' hematologic status is likely to improve with iron supplementation, leading some to suggest reconsideration of how SF cut-offs are used to diagnose ID. 16 Given this plateau behaviour, it is important to understand whether current clinically implemented SF reference intervals accurately represent the point at which the SF level begins to be associated with a decline in red cell indices. Treated patients will typically experience an improvement in red blood cell indices, followed by SF increases once iron stores are replete.…”

Section: Introductionmentioning

confidence: 99%

“…8,10 As SF levels increase, red cell indices continue to improve until a plateau is reached, following which further increases in SF do not lead to further improvements in red cell indices. 16 Given this plateau behaviour, it is important to understand whether current clinically implemented SF reference intervals accurately represent the point at which the SF level begins to be associated with a decline in red cell indices. Furthermore, because the menstrual status of females alters the relationship between iron status and hematologic states, these thresholds are expected to differ with both sex and age.…”

mentioning

confidence: 99%

Data‐driven physiologic thresholds for iron deficiency associated with hematologic decline

Foy

McClung

et al. 2019

American J Hematol

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Iron-deficiency contributes to a 50% of anemia prevalence worldwide, but reference intervals for iron status tests are not optimized for anemia diagnosis. To address this limitation, we identified the serum ferritin (SF) thresholds associated with hematologic decline in iron-deficient patients, and the SF thresholds from which an SF increase was associated with hematologic improvement. Paired red blood cell and SF measurements were analysed from two adult cohorts at Massachusetts General Hospital (MGH), from 2008-2011 (N = 48 409), and 2016-2018 (N = 10 042). Inter-patient measurements in the first cohort were used to define optimal SF thresholds based on the physiologic relationship between SF and red cell measurements. Intra-patient measurements (1-26 weeks apart) in the second cohort were used to identify SF thresholds from which an SF increase was associated, with an increase in red cell measurements. The identified optimal SF thresholds varied with age, sex and red cell measure. Thresholds associated with a 5% decline in red cell index were typically in the range 10-25 ng/mL. Thresholds for younger women (18-45 year) were 5 ng/mL lower than for older women (60-95 years), and 10 ng/mL lower than for men.Thresholds from which a subsequent increase in SF was associated with a concomitant increase in red cell measure showed similar patterns: younger women had lower thresholds (15 ng/mL) than older women (25 ng/mL), or men (35 ng/mL). These results suggest that diagnostic accuracy may be improved by setting different SF thresholds for younger women, older women, and men. This study illustrates how clinical databases may provide physiologic evidence for improved diagnostic thresholds.

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Comment on Ferritin as a functional biomarker of iron status in children and young adults Markus, et al (2019) suggest lower reference limits of ferritin for children and adolescents based on the levels at which haemoglobin and red cell indices begin to fall. Having previously applied this technique within our laboratory to examine reference ranges in adults, the cited ranges were higher than expected.

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mentioning

confidence: 99%

“…Pathology reports should provide guidance on the interpretation of the results, but a single cut-off doesn't meet this need. Ranges based on the typically referred patient groups, as performed by Markus et al (2019), simplify the heterogeneity of conditions that impact ferritin. As demonstrated in this adult population, this may lead to over-diagnosis in those without comorbidities.…”

mentioning

confidence: 99%

Comment on Ferritin as a functional biomarker of iron status in children and young adults

Crispin

2019

Br J Haematol

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Ferritin as a functional biomarker of iron status in children and young adults

Cited by 13 publications

References 2 publications

When age really matters; ferritin reference intervals during infancy revisited

When age really matters; ferritin reference intervals during infancy revisited

Data‐driven physiologic thresholds for iron deficiency associated with hematologic decline

Comment on Ferritin as a functional biomarker of iron status in children and young adults

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