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The Use of Ferritin to Identify Critically Ill Patients With Secondary Hemophagocytic Lymphohistiocytosis*

Grangé, Steven MD; Buchonnet, Gérard MD; Besnier, Emmanuel MD; Artaud-Macari, Elise MD; Beduneau, Gaetan MD; Carpentier, Dorothée MD; Dehay, Julien MD; Girault, Christophe MD; Marchalot, Antoine MD; Guerrot, Dominique MD, PhD; Tamion, Fabienne MD, PhD

doi: 10.1097/CCM.0000000000001878
Online Clinical Investigations
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Objectives: Thrombocytopenia is a common, multifactorial, finding in ICU. Hemophagocytosis is one of the main explanatory mechanisms, possibly integrated into hemophagocytic lymphohistiocytosis syndrome, of infectious origin in the majority of cases in ICU. The hemophagocytic lymphohistiocytosis is probably underdiagnosed in the ICU, although it is associated with dramatic outcomes. The main objectives of this work were to identify the frequency of secondary hemophagocytic lymphohistiocytosis, and the main prognostic factors for mortality.

Design/Setting: We conducted a retrospective observational study in all adult patients admitted with suspected or diagnosed hemophagocytic lymphohistiocytosis, between January 1, 2000, and August 22, 2012.

Patients: A total of 106 patients (42%) had significant hemophagocytosis on bone marrow examination, performed for exploration of thrombocytopenia, bicytopenia, or pancytopenia.

Measurements and Main Results: The median age was 56 (45–68) and the median Simplified Acute Physiology Score 2 was 55 (38–68). The main reason for ICU admission was hemodynamic instability (58%), predominantly related to sepsis (45% cases). The main precipitating factor found was a bacterial infection in 81 of 106 patients (76%), including 32 (30%) with Escherichia coli infection. Forty six of 106 patients (43%) died in the ICU. They were significantly older, had higher Simplified Acute Physiology Score 2, plasma lactate deshydrogenase bilirubin, and serum ferritin. The fibrinogen and the percentage of megakaryocytes were significantly lower in nonsurvivors when compared with survivors. In multivariate analysis, only serum ferritin significantly predicted death related to hemophagocytosis. A serum ferritin greater than 2,000 μg/L predicted death with a sensitivity of 71% and a specificity of 76%. A decreased percentage of megakaryocytes also predicted patient death in the ICU.

Conclusions: Hemophagocytosis is common in thrombocytopenic patients with sepsis, frequently included in a postinfectious hemophagocytic lymphohistiocytosis setting. Our study reveals that ferritin could be a reliable prognostic marker in these patients, and hold particular interest in discussing a specific treatment for hemophagocytic lymphohistiocytosis.

1Medical Intensive Care Unit, Rouen University Hospital, Rouen, France.

2Department of Hematology, Rouen University Hospital, Rouen, France.

3Department of Nephrology, Rouen University Hospital, Rouen, France.

*See also p. 2119.

This work was performed at the Medical Intensive Care Unit, Rouen University Hospital, Rouen, France.

Dr. Girault received funding from Fisher & Paykel Healthcare. The remaining authors have disclosed that they do not have any potential conflicts of interest.

For information regarding this article, E-mail: stevengrange@gmail.com

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