|Year : 2021 | Volume
| Issue : 1 | Page : 5-6
Hyperferritinemia: An important maker in sepsis
Govind Benakatti, Javed Ismail
Department of Pediatric Intensive Care, NMC Royal Hospital, Abu Dhabi, UAE
|Date of Submission||06-Nov-2020|
|Date of Acceptance||18-Nov-2020|
|Date of Web Publication||08-Jan-2021|
Dr. Govind Benakatti
Department of Pediatric Intensive Care, NMC Royal Hospital, Abu Dhabi
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Benakatti G, Ismail J. Hyperferritinemia: An important maker in sepsis. J Pediatr Crit Care 2021;8:5-6
Ferritin, an iron-binding protein, is primarily known as a storage form of iron. Traditionally, low ferritin levels indicate iron deficiency and high levels indicate hemochromatosis. Intracellular free iron levels are regulated by binding with ferritin which prevents iron-mediated oxidative damage. Recently, there has been a growing body of evidence on its role as an acute phase reactant in inflammation. Elevated serum ferritin levels have been demonstrated in various inflammatory states such as sepsis, immune dysregulation like hemophagocytic syndromes, macrophage-activation syndrome, neurodegenerative diseases, and malignancies. During sepsis and other bacterial infections, ferritin binds free iron in order to deprive bacteria thriving on it and thereby aids to contain infection. This helps to prevent oxidative damage to host cells as well. Ferritin acts as a local cytokine amplifying the inflammatory response by increasing expression of several pro-inflammatory cytokines such as inducible nitric oxide synthase, interleukin-1β, and RANTES. In addition, complex feedback mechanisms exist between ferritin and the cytokines. On the one hand, cytokines can induce ferritin expression, whereas on the other hand, ferritin can induce the expression of both pro- and anti-inflammatory cytokines. Hence, a dysregulated response or a sustained activation could lead to a feed-forward loop resulting in persistent activation of macrophages presenting with various manifestations of hyperferritinemic syndrome. This feed-forward loop mechanism resulting in sustained macrophage activation has been shown in response to viruses, bacterial components, and free hemoglobin. Hyperferritinemic sepsis due to various etiologies such as dengue, COVID-19, and bacterial infections has been correlated with severe form of disease and poor outcomes., Hyperferritinemic syndromes encompass various etiologies such as severe sepsis and inflammatory and rheumatological diseases which present with hyperferritinemia and shared clinical and laboratory features. These features include at least five of the following eight criteria: fever, splenomegaly, cytopenia, elevated triglyceride, hypofibrinogenemia, low or absent NK cell activity, hemophagocytosis, and increased soluble CD25.
Levels of ferritin have been found to correlate with severity of inflammation and high levels are associated with mortality., Apart from diagnostic importance, ferritin as a prognostic marker is getting wider recognition. Various cutoff levels of serum ferritin have been used to predict clinical outcomes. Ferritin levels above 3000 ng/mL were predictive of intensive care needs and mortality., In the current issue of the Journal of Pediatric Critical Care, Sarkar et al. in their study peak ferritin levels on day 1–3 postintensive care unit admission were found to have had high predictive value for mortality (sensitivity: 96.7% and specificity: 88%). With high prevalence of iron deficiency anemia in India, the cut-off value of ferritin with regard to disease severity and poor outcome in intensive care conditions could be lower than that seen developed countries., Hence, there seems to be a considerable variation in the threshold levels of ferritin, and therefore, the cutoff value needs to be further explored in the context of various sepsis subcohorts. Identification of patients using such cutoff values could help in prognostication and early initiation of disease-modifying therapies like immunomodulators.
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