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Incidence and risk factors of reactive histiocytic hyperplasia with hemophagocytosis in medical intensive care patients


Reactive histiocytic hyperplasia with hemophagocytosis (HHH) is characterised by a systemic proliferation of non-neoplastic histiocytes with phagocytosis of hemopoietic cells. HHH is mainly associated with virus infections, sepsis, hematologic malignancies or carcinomas.


To determine incidence and risk factors of HHH in patients dying in the intensive care unit (ICU).


We retrospectively analyzed clinical data and autopsy findings of patients (n = 107), who died in our medical ICU. Data included age, sex, medical history, reason for last admission, diagnosis, APACHE II-score, TISS-score and SOFA-score, transfusion requirements, complications, relevant laboratory findings as well as the cause of death. Bone marrow samples obtained at autopsy were histochemically stained with hematoxylin-eosin and prussian blue reaction. Immunohistochemistry with monoclonal antibodies against CD68, CD61 and myeloperoxidase (all DAKO, Hamburg/ Germany) was done to identify and quantify the hemopoietic cell lines mainly affected by the HHH. The hemophagocytic activity was graded from mild to severe HHH according to Suster et al. [1]. Cases showing moderate to severe hemophagocytic activity were classified as having HHH. Statistical analysis was performed using chi-square-test, correlational and logistic regression analysis.


At autopsy HHH was present in the bone marrow of 69 out of 107 (64.5%) patients: 35/107 (32.7%) had mild, 27/107 (25.2%) moderate, 7/107 (6.5%) severe HHH. The HHH correlates with the iron store and not with the cellularity of the bone marrow. In univariate analysis HHH was associated with higher APACHE II-score, SOFA-score and TISS-score, mechanical ventilation, recent blood transfusion, DIC and sepsis (P < 0.05). At autopsy histology of pneumonia and respiratory cause of death were more frequent in patients with HHH (P < 0.05).


HHH is frequent in patients dying in the ICU. HHH may contribute to the blood cytopenia often seen in ICU patients. Severity of illness, infections and blood transfusions are predictors of HHH.


  1. Suster , et al.: HumPathol 1988, 19: 705-712.

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Strauss, R., Neureiter, D., Wehler, M. et al. Incidence and risk factors of reactive histiocytic hyperplasia with hemophagocytosis in medical intensive care patients. Crit Care 6 (Suppl 1), P106 (2002).

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