Evaluating the optimal serum ferritin level to identify hemophagocytic lymphohistiocytosis in the critical care setting

Abstract

Ferritin is known to be involved in numerous physiological roles, such as iron storage, as well as various pathological conditions and in generalized inflammatory states. Hyperferritinemia is also encountered in the setting of hemophagocytic lymphohistiocytosis (HLH). Current diagnostic criteria exist to define HLH based on several clinical and biochemical markers, including the serum ferritin level. In this study, we retrospectively evaluated the value of ferritin >500 ng/mL in diagnosing HLH in 344 consecutive patients admitted to the medical intensive care unit at our hospital. Nine cases of HLH were identified. Comparison of the HLH with the non-HLH group showed that their maximum median serum ferritin level was 25,652 (range 1977-100,727 ng/mL) versus 1180 (503-85,168 ng/mL) (P < 0.001), platelets were 30 (5-92 × 10(3)/μL) versus 113 (0-507 × 10(3)/μL) (P < 0.001), absolute neutrophil counts were 2.56 (0.02-23.7 × 10(3)/μL) versus 7.7 (0.01-82.7 × 10(3)/μL) (P = 0.002), and triglycerides were 255 (156-394 mg/dL) versus 127 (17-624 mg/dL) (P = 0.002), respectively. Using a receiver operating characteristic curve, the optimal maximum serum ferritin level for the diagnosis of HLH was 3951 ng/mL, exceeding the current diagnostic cutoff set forth in the HLH-2004 guidelines. These data suggest that a higher cutoff value of ferritin level may have improved utility in the diagnosis of secondary HLH in the critical care setting.

Fatal case of macrophage activation syndrome (MAS) in a patient with dermatomyositis and cytomegalovirus (CMV) viraemia

“…Saeed et al performed a study of 344 patients admitted to the intensive care unit, nine of whom had HLH. Average ferritin for patients without HLH was 1180 µg/L and for those with HLH was 25 652 µg/L (p<0.001) 26. These authors suggest that based on their results, the threshold of ferritin should be increased to 3952 µg/L.…”

Clinical presentation and outcome of pediatric patients with hemophagocytic lymphohistiocytosis in China: A retrospective multicenter study

“…Soluble CD25 and NK activity were performed only in one or two hospitals. Secondly, the upper limit for serum ferritin detection was 1500–2500 μg/L in most institutions in China, which limited the clinical utility of ferritin because the clinicians are not able to observe its dynamic change and an optimal cut‐off value for HLH should be around 2000–3000 μg/L . Thirdly, the capacity to quickly and correctly diagnose and treat patients with HLH varies greatly among different institutions, and it is urgent to put forward a guideline which is suitable for most Chinese pediatric centers.…”

“…Secondly, the upper limit for serum ferritin detection was 1500-2500 g/L in most institutions in China, which limited the clinical utility of ferritin because the clinicians are not able to observe its dynamic change and an optimal cut-off value for HLH should be around 2000-3000 g/L. [18][19][20] Thirdly, the capacity to quickly and correctly diagnose and treat patients with HLH varies greatly among different institutions, and it is urgent to put forward a guideline which is suitable for most Chinese pediatric centers. To standardize the diagnosis and treatment of pediatric HLH in China, the Histiocytosis Study Group of the Chinese Pediatric Society will launch a 3-year-term multicenter prospective study in the early 2016, which will include more than 15 institutions.…”

Reevaluating the role of ferritin in the diagnosis of adult secondary hemophagocytic lymphohistiocytosis

“…Schram et al reported an HLH prevalence of only 17% among adults hyperferritinemic to >50 000 ng/mL and demonstrated that a wide array of other disease processes are capable of causing such profound hyperferritinemia; however, the test's performance characteristics and optimal cutoff value were not reported . Saeed et al found an optimal cutoff value of 3951 ng/mL (with sensitivity and specificity of 88% and 82%, respectively) among their adult hyperferritinemic patients, notably however their cohort included only 7 HLH patients . Our large study adds to the mounting evidence advocating for a reevaluation of how serum ferritin levels are considered and used in the diagnosis of HLH.…”

“…8 Saeed et al found an optimal cutoff value of 3951 ng/mL (with sensitivity and specificity of 88% and 82%, respectively) among their adult hyperferritinemic patients, notably however their cohort included only 7 HLH patients. 24 Our large study adds to the mounting evidence advocating for a reevaluation of how serum ferritin levels are considered and used in the diagnosis of HLH.…”