High Ferritin Levels Linked to Increased HLH Risk; Testing Urged

High Ferritin Levels Linked to Increased HLH Risk; Testing Urged
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People with high levels of the iron-storing protein ferritin may be at an increased risk for hemophagocytic lymphohistiocytosis (HLH), a new study suggests.

Thus, they should undergo additional diagnostic tests to assess their risk, the researchers said.

The study, “High serum ferritin alone as a predictor of mortality and hemophagocytic lymphohistiocytosis,” was published in eJHaem.

HLH is characterized by increased inflammation. Blood ferritin levels are often increased when the body is in an inflammatory state; as such, increased amounts of the protein may be predictive of HLH.

Of note, ferritin can be measured more cheaply and easily than other inflammation-associated proteins, so it may be useful as a first-line test.

In the new study, researchers from The Medicity Hospital, in India, analyzed data from patients at their institution who had their ferritin levels measured in 2016.

The team identified 128 people with ferritin levels higher than 500 nanograms (ng)/mL. The patients’ ages ranged from 4 to 82, with a mean age of 39.7 years. Among them, 21 — seven women and 14 men — had levels of the protein that were higher than 5,000 ng/mL.

Of the 21 individuals with very high ferritin levels, 10 (47.6%) required admission to the intensive care unit; six (28.6%) of these patients died. Mortality rates were significantly higher among the people with ferritin levels over 5,000 ng/mL compared with those with lower levels (7.5%, eight out of 107).

Because some data usually used to diagnose HLH were not available for all patients, the researchers were unable to definitively confirm the condition in most of the patients analyzed. The team also noted that data were often missing because healthcare providers did not order necessary diagnostic tests.

“Our study suggests that HLH may be underdiagnosed due to inadequate evaluation as a result of lack of awareness, cost constraints, and delayed results,” the researchers wrote.

Nonetheless, in all 21 patients with very high ferritin levels, clinical data were indicative of an HLH diagnosis — namely, increased inflammation and abnormal measurements related to liver function.

Only nine of the 21 patients (42.8%) received any form of treatment. Such treatment primarily involved steroids to reduce inflammation. The researchers speculated that, had diagnostic procedures been better, treatment could have been delivered more effectively, leading to better outcomes in terms of mortality.

“If a protocol had been in place to look for HLH in those with high ferritin at diagnosis then all 21 patients would have been properly worked up and treated and mortality could have been reduced,” the team wrote.

Overall, the data suggest “that high serum ferritin is highly predictive of mortality and morbidity and correlates well with the diagnosis of HLH,” the researchers concluded.

“High ferritin level ([higher than] 5000 ng/mL) can be used as a cautionary test to warrant further HLH work up and expedite management even before other cumbersome investigations can be done,” they wrote.

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Patrícia holds her PhD in Medical Microbiology and Infectious Diseases from the Leiden University Medical Center in Leiden, The Netherlands. She has studied Applied Biology at Universidade do Minho and was a postdoctoral research fellow at Instituto de Medicina Molecular in Lisbon, Portugal. Her work has been focused on molecular genetic traits of infectious agents such as viruses and parasites.

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