Etiologies and Short-Term Mortality in Patients with Ultraelevated Serum Ferritin

Beer, Timothy C; Vadakara, Joseph

doi:10.14423/smj.0000000000000339

Cited by 13 publications

(17 citation statements)

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“…The association between mortality rates and hyperferritinemia has been researched in a growing number of studies in the past years. [ 20 – 23 ] The poor prognosis in patients with hyperferritinemia attributed to malignancy was already reported in a previous study, [ 24 ] but we suggest that this finding can be generalized to other disease states as well. According to our study, it seems that when patients over the age of 70 years are admitted to the hospital, for whatever reason, with ferritin levels above 1000 μg/L, their chances of surviving the next 6 months are less than 50%.…”

Section: Discussionsupporting

confidence: 68%

Hyperferritinemia in the elderly can differentiate the bad from the worst

2020

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Both total-body iron stores and inflammation influence the concentration of ferritin in the blood. Ferritin as an inflammatory marker might serve as a prognostic marker in the elderly. Therefore, we characterized the clinical circumstances and long-term outcomes of hyperferritinemia (> 1000 μg/L) in hospitalized elderly patients. A retrospective analysis of elderly (> 70 years) inpatients with ferritin levels of > 1000 μg/L in a tertiary medical center during a 3-year period. We obtained both laboratory and clinical data, assessing the potential association of high ferritin levels with long-term mortality. Overall, 242 patients (median age 79 years; median ferritin level 1436 μg/L) met the inclusion criteria and were followed for a median time of 18.6 months. Clinical outcomes were dismal for the whole cohort: the diagnosis of solid malignancy occurred in 23.5% of cases while 31% had a severe infection (ranging from sepsis to septic shock). The median survival time of the whole cohort was 4.7 months only. Within the cohort, risk stratification was feasible: higher ferritin levels differentiate between groups of patients who had a poor prognosis (with either septic shock or solid malignancy) and those who had a relatively favorable prognosis (patients diagnosed as suffering from sepsis without shock and patients with iatrogenic causes for hyperferritinemia). Hyperferritinemia in elderly inpatients is associated with high rates of mortality. Within this group of patients, differential ferritin levels enable further risk stratification. High ferritin levels in the elderly can differentiate the bad from the worst.

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Section: Discussionsupporting

confidence: 68%

Hyperferritinemia in the elderly can differentiate the bad from the worst

2020

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“…An elevated serum ferritin is a marker of hemophagocytic lymphocytosis histiocytosis (HLH), macrophage activation syndrome (MAS) in rheumatic disorders, iron-overloaded states including chronic blood transfusions, and acute liver injury [14–16]. However, there are limited data on its clinical use for differentiating among infectious diseases [17, 18].…”

Section: Discussionmentioning

confidence: 99%

Hyperferritinemia as a Diagnostic Marker for Severe Fever with Thrombocytopenia Syndrome

Kim

et al. 2017

Disease Markers

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Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral disease in East Asia with high mortality. Few studies have examined markers that suggest SFTS in febrile patients. To determine useful biochemical markers for SFTS, patients aged 18 years or older with SFTS or microbiologically confirmed community-onset bacteremia with thrombocytopenia (BT) at presentation between June 2013 and December 2015 were included from two tertiary university hospitals in Republic of Korea retrospectively. Eleven patients with SFTS and 62 patients with bacteremia and thrombocytopenia were identified in the study period. Age and sex did not show significant difference among two groups. Fever was more commonly observed but comorbidities were less common in SFTS than in BT (P < 0.05, each). The areas under the curves of serum ferritin, C-reactive protein, white blood cell count, serum procalcitonin, and fibrinogen were above 0.9, indicating the discriminative power of these biomarkers (1.000, 0.991, 0.963, 0.931, and 0.934, resp., all P < 0.05). The optimal cutoff value of serum ferritin was 3,822 ng/mL in this study. These results suggest that hyperferritinemia is a typical laboratory feature of SFTS, and the serum ferritin level can be used as a marker for clinicians suspecting SFTS.

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“…For patients with serum ferritin >40,000 ng/ml, mortality was 52% after 30 days and 57% after 6 months. Sepsis was not identified as a cause of hyperferitinaemia among patients who were also suffering from malignancies (22).…”

Section: Hemophagocytic Lymphohistocytosis: Classification and Currenmentioning

confidence: 99%

Macrophage Activation-Like Syndrome: A Distinct Entity Leading to Early Death in Sepsis

Karakike

Giamarellos‐Bourboulis

2019

Front. Immunol.

250

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Hemophagocytic lymphohistocytosis (HLH) is characterized by fulminant cytokine storm leading to multiple organ dysfunction and high mortality. HLH is classified into familial (fHLH) and into secondary (sHLH). fHLH is rare and it is due to mutations of genes encoding for perforin or excretory granules of natural killer (NK) cells of CD8-lymphocytes. sHLH is also known as macrophage activation syndrome (MAS). Macrophage activation syndrome (MAS) in adults is poorly studied. Main features are fever, hepatosplenomegaly, hepatobiliary dysfunction (HBD), coagulopathy, cytopenia of two to three cell lineages, increased triglycerides and hemophagocytosis in the bone marrow. sHLH/MAS complicates hematologic malignancies, autoimmune disorders and infections mainly of viral origin. Pathogenesis is poorly understood and it is associated with increased activation of macrophages and NK cells. An autocrine loop of interleukin (IL)-1β over-secretion leads to cytokine storm of IL-6, IL-18, ferritin, and interferon-gamma; soluble CD163 is highly increased from macrophages. The true incidence of sHLH/MAS among patients with sepsis has only been studied in the cohort of the Hellenic Sepsis Study Group. Patients meeting the Sepsis-3 criteria and who had positive HSscore or co-presence of HBD and disseminated intravascular coagulation (DIC) were classified as patients with macrophage activation-like syndrome (MALS). The frequency of MALS ranged between 3 and 4% and it was an independent entity associated with early mortality after 10 days. Ferritin was proposed as a diagnostic and surrogate biomarker. Concentrations >4,420 ng/ml were associated with diagnosis of MALS with 97.1% specificity and 98% negative predictive value. Increased ferritin was also associated with increased IL-6, IL-18, IFNγ, and sCD163 and by decreased IL-10/TNFα ratio. A drop of ferritin by 15% the first 48 h was a surrogate finding of favorable outcome. There are 10 on-going trials in adults with sHLH; two for the development of biomarkers and eight for management. Only one of them is focusing in sepsis. The acronym of the trial is PROVIDE (ClinicalTrials.gov NCT03332225) and it is a double-blind randomized clinical trial aiming to deliver to patients with septic shock treatment targeting their precise immune state. Patients diagnosed with MALS are receiving randomized treatment with placebo or the IL-1β blocker anakinra.

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Etiologies and Short-Term Mortality in Patients with Ultraelevated Serum Ferritin

Cited by 13 publications

References 1 publication

Hyperferritinemia in the elderly can differentiate the bad from the worst

Hyperferritinemia in the elderly can differentiate the bad from the worst

Hyperferritinemia as a Diagnostic Marker for Severe Fever with Thrombocytopenia Syndrome

Macrophage Activation-Like Syndrome: A Distinct Entity Leading to Early Death in Sepsis

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