Introduction: Hyperferritinemia is associated with increased mortality in pediatric sepsis, multiple organ dysfunction syndrome (MODS), and critical illness. The International Histiocyte Society has recommended that children with hyperferritinemia and secondary hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS) should be treated with the same immunosuppressant/cytotoxic therapies used to treat primary HLH. We hypothesized that patients with hyperferritinemia associated secondary HLH/sepsis/MODS/MAS can be successfully treated with a less immunosuppressant approach than is recommended for primary HLH. Methods: We conducted a multi-center cohort study of children in Turkish Pediatric Intensive Care units with hyperferritinemia associated secondary HLH/sepsis/MODS/MAS treated with less immunosuppression (plasma exchange and intravenous immunoglobulin or methyl prednisolone) or with the primary HLH protocol (plasma exchange and dexamethasone or cyclosporine A and/or etoposide). The primary outcome assessed was hospital survival. Results: Twenty-three children with hyperferritinemia and secondary HLH/sepsis/MODS/MAS were enrolled (median ferritin = 6341 μg/dL, median number of organ failures = 5). Univariate and multivariate analyses demonstrated that use of plasma exchange and methyl prednisolone or intravenous immunoglobulin (n = 17, survival 100%) was associated with improved survival compared to plasma exchange and dexamethasone and/or cyclosporine and/or etoposide (n = 6, survival 50%) (P = 0.002). Conclusions: Children with hyperferritinemia and secondary HLH/sepsis/MODS/MAS can be successfully treated with plasma exchange, intravenous immunoglobulin, and methylprednisone. Randomized trials are required to evaluate if the HLH-94 protocol is helpful or harmful compared to this less immune suppressive and cytotoxic approach in this specific population.

Objective: Thrombocytopenia-associated multiple organ failure can lead to high mortality in critically ill children, possibly related to consequences of thrombotic microangiopathy . Plasma exchange therapy may improve thrombotic microangiopathy . The purpose of this observational cohort study is to describe whether there is an association between use of plasma exchange therapy and outcome in the Turkish thrombocytopenia-associated multiple organ failure network. Setting-Interventions: We performed a retrospective cohort analysis in patients with thrombocytopenia-associated multiple organ failure at three different PICUs comparing those who received plasma exchange (+) plus standard therapies with those who did not receive plasma exchange (–) and only received standard therapies. Results: Among 42 of the enrolled patients with thrombocytopenia-associated multiple organ failure, all had a primary or secondary sepsis diagnosis. Fifteen received plasma exchange therapy (PE [+] group) and 27 received standard medical treatment without plasma exchange (PE [–] group). The mean age was 17.69 months (8.24–54.22) in the PE (+) group and 13.46 months (6.47–20.55) in the PE (–) group. Age (p = 0.232), gender (p = 0.206), thrombocyte count (p = 0.09), Organ Failure Index score (p = 0.111), and pediatric logistic organ dysfunction score (p = 0.177) at admission were not statistically different between groups. The overall 28-day mortality was higher in the PE (–) group (70.37%) compared with the PE (+) group (26.67%) (univariate p = 0.006; multivariate controlling for pediatric logistic organ dysfunction, Organ Failure Index, Pediatric Risk of Mortality scores, and neurological failure p = 0.048). Length of stay was increased in the PE (+) group (p = 0.004). Conclusions: The positive association found between use of plasma exchange therapy and improved survival supports the potential of this therapy in Turkish children with thrombocytopenia-associated multiple organ failure. The positive, although less so, associated treatment effect observed after controlling for illness severity provides further rationale for performing a randomized controlled trial in the pediatric Turkish thrombocytopenia-associated multiple organ failure network. Sample size calculations call for a 100-patient trial with a pre hoc interim analysis after enrollment of 50 patients with thrombocytopenia-associated multiple organ failure.