Background/Purpose

Macrophage Activation Syndrome (MAS) is a syndrome similar to Familial Hemophagocytic Lymphohistiocytosis (HLH) characterized by increased proliferation and activity of T-cells and macrophages leading to massive systemic inflammation, multi-organ system failure, and often significant morbidity/mortality. Elevated serum ferritin is part of the diagnostic criteria for MAS/HLH and studies have shown that extremely elevated levels of serum ferritin have a high specificity for MAS. We sought to determine the correlation between significantly elevated ferritin levels (>2000) and in-hospital mortality as well as associated presence of MAS among adult inpatients.

Methods

Using Cerner EHR, patients were selected for study inclusion based on serum ferritin levels >2000 obtained during hospital admissions. Patients with hemoglobinopathy associated ferritin elevation were excluded.  Patient charts during hospitalizations corresponding to the elevated serum ferritin were reviewed for mortality, diagnostic criteria for MAS, and treatment interventions. Patients were determined to have likely MAS based on either 1) whether current case definition criteria for HLH were met with at least 5 of the following: fever >100.4 degrees F, splenomegaly, two or more cytopenias (Hgb <9.0 g/dL, Platelets <100 x10⁹/L, ANC <1.0x10⁹/L), hypertriglyceridemia (fasting >265 mg/dl), hypofibrinogenemia (<1.5 g/L),  pathology demonstrating hemophagocytosis, low/absent NK-cell-activity, hyperferritinemia, or high-soluble interleukin-2-receptor levels; or 2) given that many patients did not have pathology or MAS immunologic parameters checked,  if they met  4 out of the  5 clinical/laboratory criteria : fever, splenomegaly, two or more cytopenias, hypertriglyceridemia, and  hypofibrinogenemia or new coagulopathy defined as INR >1.5 if no fibrinogen level available.

Results

Patients were stratified into groups by peak serum ferritin levels :  2-5,000, 5-10,000, 10-20,000, and >20,000. Mortality rates were 70/370 (19%) in the 2-5000 group, 28/78 (36%) in the 5-10,000 group 11/40 (28%) in the 10-20,000 group, 15/39 (39%) in the >20,000 group. A total of 48 patients met the designated criteria for MAS, comprising 2% of patients in the 2-5,000 group; 6% of the 5-10,000 group; 30% of the 10-20,000 group and 61% of the >20,000 group. In addition to treatment with corticosteroids, 29 of these 48 patients received treatment with the IL-1 inhibitor anakinra, 10 of whom died during the hospitalization (in-hospital mortality of 34.5%); among the 19 patients with identified MAS who did not receive anakinra as part of their treatment there were 15 in-hospital deaths (in-hospital mortality of 79%).

Conclusion

Our results demonstrate a correlation between elevations in serum ferritin levels and increased in-hospital mortality in adult patients.  Furthermore, our results suggest that at least part of the increased mortality observed in patients with extremely elevated serum ferritin is attributable to unrecognized or undertreated MAS.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/elevated-serum-ferritin-levels-in-adult-inpatients-as-a-predictor-of-in-hospital-mortality-and-association-with-macrophage-activation-syndrome/