Extreme Hyperferritinemia:  Causes and Impact on Diagnostic Reasoning

Area of Science:

• Hematology
• Clinical Pathology

Background:

• Hyperferritinemia, or elevated serum ferritin, can indicate inflammation, infection, iron overload, or rare conditions like hemophagocytic lymphohistiocytosis (HLH).
• A historical association exists between extreme hyperferritinemia and HLH, though HLH accounts for a minority of hyperferritinemic states.

Purpose of the Study:

• To identify the conditions most frequently associated with hyperferritinemia.
• To evaluate the diagnostic value of extreme hyperferritinemia for identifying HLH.

Main Methods:

• Retrospective analysis of 65,536 serum ferritin levels over five years at the University of Minnesota Hospital.
• Focused analysis on 86 cases with ferritin levels exceeding 10,000 ng/mL, comprising pediatric (22%) and adult (78%) patients.

Main Results:

• The primary causes of hyperferritinemia were chronic transfusion (35%), liver disease (27%), and hematologic malignancy (16%).
• Other causes included solid tumors, infections, macrophage activation syndrome, and HLH (primary and secondary), collectively accounting for 22% of cases.

Conclusions:

• While extreme hyperferritinemia can be linked to HLH, its positive predictive value for diagnosing HLH is low.
• Clinicians should consider more common etiologies of hyperferritinemia before suspecting HLH.