Hyperferritinemia—A Clinical Overview

Sandnes, Miriam; Ulvik, Rune J.; Vorland, Marta; Reikvam, Håkon

doi:10.3390/jcm10092008

Cited by 73 publications

(93 citation statements)

References 149 publications

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“…In the preclinical stage, when a convincing correlation between elevated Tsat and ferritin may be absent, the initial diagnostic workup of suspected hemochromatosis often proves to be difficult, not least because hyperferritinemia is a non-specific marker of pathological iron overload [16]. With Tsat being an important marker for genetic penetrance in HFE hemochromatosis and a measure of iron accumulation rate, our results confirm C282Y homozygosity as a superior cause of abnormally increased iron accumulation at the population level of this specific area.…”

Section: Discussionmentioning

confidence: 99%

HFE Genotype, Ferritin Levels and Transferrin Saturation in Patients with Suspected Hereditary Hemochromatosis

Sandnes

Vorland

Ulvik

et al. 2021

Genes

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HFE hemochromatosis is characterized by increased iron absorption and iron overload due to variants of the iron-regulating HFE gene. Overt disease is mainly associated with homozygosity for the C282Y variant, although the H63D variant in compound heterozygosity with C282Y (C282Y/H63D) contributes to disease manifestation. In this observational study, we describe the association between biochemical findings, age, gender and HFE genotype in patients referred from general practice to a tertiary care referral center for diagnostic workup based on suspected hemochromatosis due to persistent hyperferritinemia and HFE variants. C282Y and H63D homozygosity were, respectively, the most and least prevalent genotypes and we found a considerable variation in transferrin saturation and ferritin levels independent of HFE genotype, which may indeed represent a diagnostic challenge in general practice. While our results confirm C282Y homozygosity as the major cause of iron accumulation, non-C282Y homozygotes also displayed mild to moderate hyperferritinemia with median ferritin levels at 500-700 µg/L, well above the reference cut-off. Such findings have traditionally been ignored in the clinic, and initiation of iron depletion has largely been restricted to C282Y homozygotes. Nevertheless, superfluous iron can aggravate pathogenesis in combination with other diseases and risk factors, such as inflammation, cancer and hepatopathy, and this possibility should not be neglected by clinicians.

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Section: Discussionmentioning

confidence: 99%

HFE Genotype, Ferritin Levels and Transferrin Saturation in Patients with Suspected Hereditary Hemochromatosis

Sandnes

Vorland

Ulvik

et al. 2021

Genes

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“…According to a newly published review, the rate of rheumatologic/inflammatory diseases in patients with hyperferritinemia, which includes general hospital data, ranges from 1.8% to 32.6% [14]. Our results indicate that the most common causes of hyperferritinemia are rheumatologic diseases and infections, which were identified in 59.1 and 27.3%, respectively.…”

Section: Discussionmentioning

confidence: 64%

“…It is difficult to conclude a definite prevalence or incidence rate of hyperferritinemia, since different levels for the description of hyperferritinemia have been used in the previous studies [5][6][7][8][9][10][11]. The prevalence and causes of hyperferritinemia vary according to ethnic differences, genderage, outpatient or inpatient of the study population, adult or pediatric age group, whether it was done in a general hospital or not, and the cut-off value for ferritin [14]. In a study evaluating patients with serum ferritin levels greater than 3000 μg/L in Canada over 1 year (from general + hematology + malignancy database), hyperferritinemia was identified in 141 of 25,600 ferritin measurements [7].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of hyperferritinemia causes in rheumatology practice: a retrospective, single-center experience

Teke

Cansu²,

Korkmaz

2021

Rheumatol Int

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Hyperferritinemia may develop due to various reasons such as inflammation, infection, or malignancy. The purpose of the study to explore the prevalence and to figure out the causes of general hyperferritinemia and extreme hyperferritinemia as detected through the ferritin measurements requested by the rheumatology department. Adult patients at the age of 18 years and older with at least one serum ferritin level measurement at or above 500 ng/mL as requested by the rheumatology department between January 2010 and December 2019 were evaluated retrospectively. Hyperferritinemia was detected in 4.7% of 11,498 serum ferritin tests. The mean age of 242 patients found to have hyperferritinemia was 53.7 ± 17.1 years; of the patients, 63.2% were female, and the mean serum ferritin value was 2820 ± 5080 ng/mL. The most common cause of hyperferritinemia was rheumatological diseases with a ratio of 59.1%, which was followed by infections, iron overload, and solid malignancy. Among the rheumatologic diseases, adult-onset Still's disease (AOSD), rheumatoid arthritis, and vasculitis were the cause accounting for hyperferritinemia. Ferritin levels were significantly higher in the AOSD group compared to the other rheumatologic disease groups (p < 0.0001). While extreme hyperferritinemia (ferritin ≥ 10,000 ng/mL) rate in our cohort was 0.2%, the most common cause was AOSD (15/17). In patients with hyperferritinemia, 3 month mortality was found to be 8.7%. CRP level was identified as the only independent predictor for the 3 month mortality in all patients [OR 1.088 (95% CI 1.004-1.178), p = 0.039]. Although rheumatologic disease activation and infections are the most common causes, the other causes should also be considered for the differential diagnosis.

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“…Although hyperferritinemia is seen as a result of acute phase reactions usually, clinical interpretation of it often proves to be complex [ 29 ]. Accumulated data suggest that ferritin acts as a direct mediator between signaling molecules and the immune system, because the H subunit of ferritin plays a vital role in this mechanism [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Hemophagocytosis, hyper-inflammatory responses, and multiple organ damages in COVID-19-associated hyperferritinemia

Dong

Gao

et al. 2021

Ann Hematol

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Hyperferritinemia comes to light frequently in general practice. However, the characteristics of COVID-19-associated hyperferritinemia and the relationship with the prognosis were not well described. The retrospective study included 268 documented COVID-19 patients. They were divided into the hyperferritinemia group (≥ 500 µg/L) and the non-hyperferritinemia group (< 500 µg/L). The prevalence of fever and thrombocytopenia and the proportion of patients with mechanical ventilator support and in-hospital death were much higher in the hyperferritinemia group (P < 0.001). The hyperferritinemia patients showed higher median IL-6, D-dimer, and hsCRP (P < 0.001) and lowered FIB level (P = 0.036). The hyperferritinemia group had a higher proportion of patients with AKI, ARDS, and CSAC (P < 0.001). According to the multivariate analysis, age, chronic pulmonary disease, and hyperferritinemia were found to be significant independent predictors for in-hospital mortality [HR 1.041 (95% CI 1.015–1.068), P = 0.002; HR 0.427 (95% CI 0.206–0.882), P = 0.022; HR 6.176 (95% CI 2.447–15.587), P < 0.001, respectively]. The AUROC curve was 0.88, with a cut-off value of ≥ 971 µg/L. COVID-19 patients with hyperferritinemia had a high proportion of organ dysfunction, were more likely to show hyper-inflammation, progressed to hemophagocytic lymphohistiocytosis, and indicated a higher proportion of death.

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Hyperferritinemia—A Clinical Overview

Cited by 73 publications

References 149 publications

HFE Genotype, Ferritin Levels and Transferrin Saturation in Patients with Suspected Hereditary Hemochromatosis

HFE Genotype, Ferritin Levels and Transferrin Saturation in Patients with Suspected Hereditary Hemochromatosis

Evaluation of hyperferritinemia causes in rheumatology practice: a retrospective, single-center experience

Hemophagocytosis, hyper-inflammatory responses, and multiple organ damages in COVID-19-associated hyperferritinemia

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