Multifactorial risk analysis of bone marrow histiocytic hyperplasia with hemophagocytosis in critically ill medical patients—A postmortem clinicopathologic analysis

OBJECTIVE: Systematic studies of the prevalence and risk factors of histiocytic hyperplasia with hemophagocytosis (HHH) in critically ill patients are lacking. The aim of our study was a) to determine the frequency and intensity of HHH in the bone marrow of patients who died on the medical intensive care unit; b) to analyze morphologic bone marrow changes; and c) to identify possible risk factors and their interactions in the pathogenesis of HHH. DESIGN: A retrospective observational analysis of clinical data and autopsy findings including histologic and immunohistological analysis of bone marrow to characterize cellularity, siderosis, hemophagocytosis, and T-cell infiltrates. SETTING: The medical intensive care unit of a university hospital. PATIENTS: Patients were 107 consecutive patients who died and underwent autopsy. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: HHH was identified in 69 of the 107 patients (64.5%). Moderate to severe HHH was present in 35 of the 107 bone marrows. Univariate risk factor analysis showed that HHH was associated with various intrinsic and extrinsic factors. However, multivariate analysis identified the intensity of therapeutic interventions--represented by the Therapeutic Intervention Scoring System--as the only positive, and cardiovascular disease as the only significant negative, predictor of HHH (p <.05). Routine laboratory tests were of no value in predicting the presence of HHH. The intensity of HHH correlated significantly with siderosis and T-cell infiltrates (p <.05) but not with bone marrow cellularity. CONCLUSIONS: HHH is common in medical intensive care unit nonsurvivors. Treatment intensity and a noncardiovascular cause of death are predictors of HHH. Sepsis and blood transfusion may have a synergistic effect on the triggering of HHH. HHH in bone marrow is associated with enhanced T-cell infiltrates, suggesting that T cells may play an important role in its mediation.