Very high serum ferritin levels are associated with increased mortality and critical care in pediatric patients

Bennett, Tellen D.; Hayward, Kristen; Farris, Reid; Ringold, Sarah; Wallace, Carol A.; Brogan, Thomas V.

doi:10.1097/pcc.0b013e31820abca8

Cited by 98 publications

(80 citation statements)

References 14 publications

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“…Finally, other causes of ferritin increase, such as iatrogenic iron overload, could not be excluded, but appeared unlikely. Ferritin has recently received growing attention in human medicine as a potential prognostic marker in critical care patients (Bennett et al, 2011). In our study, non-survivors presented a significantly higher ferritin concentration than survivors, suggesting that these animals could have had a more severe APR, or a greater degree of ferritin leakage associated with tissue damage or haemolysis.…”

Section: Discussionmentioning

confidence: 68%

Serum amyloid A, haptoglobin, and ferritin in horses with colic: Association with common clinicopathological variables and short-term outcome

Dondi

Lukacs

Gentilini

et al. 2015

The Veterinary Journal

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Section: Discussionmentioning

confidence: 68%

Serum amyloid A, haptoglobin, and ferritin in horses with colic: Association with common clinicopathological variables and short-term outcome

Dondi

Lukacs

Gentilini

et al. 2015

The Veterinary Journal

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“…Third, although the optimal cutoffs derived using the Youden Method add statistical clarity to our study, previous investigators have reported utility with other CRP and ferritin thresholds cutoffs. 3–10 For example, Seattle Children’s Hospital reported a stepwise risk when ferritin levels reached 1,000 ng/mL or 3,000 ng/mL whereas a Brazilian study noted increased risk at 500 ng/mL. More studies are required to determine the reason for these differences in cutoff values.…”

Section: Discussionmentioning

confidence: 99%

“…12 In a study of all hospitalized children at Seattle Children’s Hospital, ferritin levels > 1,000 ng/mL and > 3,000 ng/mL were associated with a stepwise increase in the risk of subsequent admission to the pediatric intensive care unit or death over the next five years regardless of cancer, rheumatologic disease, or hemolytic anemia status. 10 …”

Section: Introductionmentioning

confidence: 99%

A Systemic Inflammation Mortality Risk Assessment Contingency Table for Severe Sepsis*

Carcillo

Sward

Halstead

et al. 2017

Pediatric Critical Care Medicine

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Objective We tested the hypothesis that a c-reactive protein (CRP) and ferritin based systemic inflammation contingency table can track mortality risk in pediatric severe sepsis. Design Prospective cohort study Setting Tertiary Pediatric Intensive Care Unit Patients Children with 100 separate admission episodes of severe sepsis were enrolled. Interventions Blood samples were attained on day two of sepsis and bi-weekly for biomarker batch analysis. A 2 × 2 contingency table using CRP and ferritin thresholds was developed. Measurements and Main Results A CRP of 4.08 mg/dL and a ferritin of 1,980 ng/mL were found to be optimal cutoffs for outcome prediction at first sampling (n = 100) using the Youden Index. PICU mortality was increased in the ‘High risk’ CRP ≥ 4.08 mg/dL and Ferritin ≥ 1,980 ng/mL category (6/13, 46.15%) compared to the ‘Intermediate risk’ CRP ≥ 4.08 mg/dL and Ferritin < 1,980 ng/mL or CRP < 4.08 mg/dL and Ferritin ≥ 1,980 ng/mL categories (2/43, 4.65%), and the ‘Low risk’ CRP < 4.08 mg/dL and Ferritin < 1,980 ng/mL category (0/44, 0%) (OR 36.43 [95% CI: 6.16–215.21]). The ‘High risk’ category was also associated with the development of Immunoparalysis (OR 4.47 [95% CI 1.34–14.96]) and Macrophage Activation Syndrome (OR 24.20 [95% CI 5.50–106.54]). Sixty three children underwent sequential blood sampling; those who were initially in the ‘Low risk’ category (n = 24) and those who subsequently migrated to (n =19) to the ‘Low risk’ category all survived, whereas those who remained in the ‘At risk’ categories had increased mortality (7/20 = 35%; p < 0.05). Conclusions A CRP and ferritin based contingency table effectively assessed mortality risk. Reduction in systemic inflammation below a combined threshold CRP of 4.08 mg/dL and ferritin of 1,980 ng / mL appeared to be a desired response in children with severe sepsis.

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“…Of note, a recent examination of 55 biomarkers in Ebola hemorrhagic fever (EHF) patients indicated that elevations in serum thrombomodulin and serum ferritin were both associated with hemorrhage and mortality 51,52 . Elevation of serum ferritin has been shown to correlate with mortality among pediatric patients with MAS in multiple settings 53,54 .…”

Section: Introductionmentioning

confidence: 99%

Rationale for Adjunctive Therapies for Pediatric Sepsis Induced Multiple Organ Failure

Podd

Simon

Lopez

et al. 2017

Pediatric Clinics of North America

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Adjunctive therapies have been proposed for use in at least 5 inflammation pathobiology phenotypes in pediatric sepsis-induced multiple organ failure (MOF). Here, we provide host-pathogen interaction prototypes to facilitate understanding of the rationale for personalized therapy in these phenotypes. Meningococcemic sepsis and Shiga-like toxin-associated atypical Hemolytic Uremic Syndrome sepsis result in thrombocytopenia and MOF due to endothelial dysfunction and formation of small vessel thromboses that can respond to plasma exchange and C5a monoclonal antibody therapy. H1N1 Influenza A sepsis is associated with immune paralysis that can result in opportunistic secondary infection with invasive methicillin resistant Staphylococcus aureus (MRSA) and MOF that can respond to Granulocyte Macrophage Colony Stimulating Factor therapy. Hyperleukocytosis-associated MOF is associated with critical Bordetella Pertussis pulmonary hypertension and cardiovascular collapse which can respond to leukoreduction therapy. Epstein Barr Virus lymphoproliferative disease-associated sequential MOF has high levels of soluble-Fas Ligand that cause liver failure, and can respond to anti-CD20 monoclonal antibody therapy. Viral hemorrhagic fevers such as Ebola or Dengue can lead to macrophage activation syndrome characterized by hyperferritinemia, hepatobiliary dysfunction and disseminated intravascular coagulation (DIC)-related MOF that can theoretically respond to anti-inflammatory therapies. We discuss the literature on adjunctive anti-inflammatory and immune modulation therapies that, in addition to traditional organ support and infection source control, might be part of a personalized precision medicine approach to reverse of each of these inflammatory pathobiology phenotypes.

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Very high serum ferritin levels are associated with increased mortality and critical care in pediatric patients

Abstract: In this pediatric population, with serum ferritin levels of >3000 ng/mL, there was increased risk for both receipt of critical care and subsequent death.

Cited by 98 publications

References 14 publications

Serum amyloid A, haptoglobin, and ferritin in horses with colic: Association with common clinicopathological variables and short-term outcome

Serum amyloid A, haptoglobin, and ferritin in horses with colic: Association with common clinicopathological variables and short-term outcome

A Systemic Inflammation Mortality Risk Assessment Contingency Table for Severe Sepsis*

Rationale for Adjunctive Therapies for Pediatric Sepsis Induced Multiple Organ Failure

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