Hyperferritinemia in Hemophagocytic Lymphohistiocytosis: A Single Institution Experience in Pediatric Patients

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is an inflammatory condition that may run a rapid fatal course and calls for prompt diagnosis. Early intervention with steroids and other immunosuppressive drugs can contain the disease process and favours positive outcome. Ferritin ≥500 ng/ml is a HLH diagnostic criterion. We evaluated the diagnostic potential of admission ferritin, in children with HLH. Pediatric patients of a referral teaching hospital from Feb 2010-Oct 2013 having been investigated for ferritin on admission were included. HLH was confirmed when patients had clinical features and met 5/8 diagnostic criteria of the revised 2004 HLH guidelines. Ferritin was estimated on Cobas e411 by electrochemiluminiscence, with a measuring range of 0.5-2000 ng/ml. Dilutions were made when linearity exceeded and absolute values were reported. 905 on-admission ferritin investigations were reviewed out of which 346 values ≥500 ng/ml. Hyperferritinemia was seen in HLH/MAS (macrophage activation syndrome) [HLH group, median age 4 year 4 month, 59% male] and in systemic lupus erythematosus, sepsis, juvenile idiopathic arthritis, impending HLH, haemolytic anemias and malignancy [non-HLH group, median age 4 year 6 month, 60% male]. Of 346, 72 cases of hyperferritinemia were diagnosed with secondary HLH while one patient had primary HLH. 13/73 patients expired. The median ferritin level of the HLH group was significantly higher [6556 (2402-11,734) ng/ml] compared to non-HLH group [median 1175 (943-2000) ng/ml] ( < 0.0001). Receiver operator characteristics curve analysis revealed optimal admission ferritin of 3120 ng/ml as the cut-off with sensitivity of 70% and specificity of 88.9% for HLH diagnosis, exceeding the currently prescribed cut-off of 500 ng/ml. Hyperferritinemia below 3120 ng/ml has higher negative predictive value to rule out secondary HLH on admission in the study population of children predominantly diagnosed with infection associated HLH than the prescribed cut-off as per the 2004 guidelines. This may prove to be beneficial to alert physicians for prompt intervention which considerably decreases mortality in this often fatal condition.

Pediatric Hemophagocytic lymphohistiocytosis: A rarely diagnosed entity in a developing country

“…Upon admission, 28% of our population had ferritin >10,000 ng/ml which has reported a sensitivity and specificity above 80%. 20,21 Hemophagocytes were found in bone marrow (BM) in 57% of patients which is in accordance with literature reports depending on the time of the BM aspirate, this finding is reported between 40% and 80%. 2,22 In our population hemophagocytes were not sought in tissues other than BM since this practice is not protocolized in our institution.…”

Hemophagocytic lymphohistiocytosis: a case series analysis in a pediatric hospital

“… 20 Hyperferritinemia is a hallmark of HLH, as it increases the sensibility and specificity for the disease diagnosis. 21 , 22 Although hyperferritinemia is a critical factor in establishing the HLH diagnosis, there was no statistical significance between the ferritin levels and the death rate ( p = 0.9) in our case series.…”

Clinical and laboratory characteristics of hemophagocytic lymphohistiocytosis induced by Leishmania infantum infection

“…It is also a positive acute phase reactant to reflect inflammatory conditions. The extreme elevations of serum ferritin may result from the activation of inflammatory cytokines that mediate the acute phase response, but in turn to mediate the pro-inflammatory process by inducing the expression of pro-inflammatory cytokines [ 26 ]. Thus, iron overload with hepatosplenomegaly detected in this study may reflect the severe conditions in the Leishmania infection and its associated HLH.…”