Diagnostic and Prognostic Significance of High Hyperferritinemia in Hemophagocytic Syndrome
RC Reed, K Hutchinson, PM Rainey, MH Wener. University of Washington, Seattle, WA
Background: Hemophagocytic syndrome (HPS) and Still's disease (systemic onset juvenile chronic arthritis) present a diagnostic challenge, since many symptoms are nonspecific. An important diagnostic tool is the serum ferritin concentration, which can reach levels in excess of 100,000 ng/mL. However, the sensitivity and prognostic significance of high hyperferritinemia in the diagnosis and evaluation of HPS has not been examined. Additionally, the ferritin immunoassay is subject to a high dose hook effect at these concentrations, potentially confounding interpretation of this value.
Design: We examined the characteristics, including eventual diagnosis and survival time, of patients with high hyperferritinemia showing a hook effect (>99,000 ng/mL), drawing from the results of 37,185 ferritin tests performed over a three-year period. Hook effect was further investigated experimentally, to characterize the performance of the ferritin immunoassay.
Results: Nine patients, with a total of 15 (0.04%) clinical samples, had ferritin levels greater than 99,000 ng/mL, sufficient to yield a hook effect. Of eight patients for whom clinical information was available, six had documented HPS; of these, 4/6 were likely related to EBV or CMV infection, and 2/6 were secondary to hematologic malignancy (one T-cell lymphoma and one NK cell leukemia). Another patient presented with acute hepatitis, possibly ischemic, and one patient with bacterial endocarditis and subarachnoid hemorrhage exacerbating chronic diabetic renal disease. Five of the eight died less than a month after presentation with hyperferritinemia, while two with viral-related HPS are alive at least one year after diagnosis, and the patient with acute hepatitis was discharged in good condition. The hook effect threshold was similar in patient and experimental samples, with assay results decreasing predictably as the ferritin concentration increased. To avoid reporting falsely low results due to the hook effect, samples with results >300 ng/mL can be automatically diluted and repeated. At this cut-off, ferritin concentrations up to >500,000 ng/mL are accurately detected.
Conclusions: HPS and Still's disease are diagnostic challenges, and hyperferritinemia is an important criterion. High hyperferritinemia predicts HPS in our series, though acute hepatotoxicity and other inflammatory conditions may also yield very high ferritin concentrations. Ferritin levels above 100,000 ng/mL were associated with a high mortality rate. We describe a new, automated method to detect and prevent hook effect.
Wednesday, March 11, 2009 1:00 PM
Poster Session VI # 236, Wednesday Afternoon