Objectives

Some children with sepsis exhibit a sustained hyperinflammatory response that can trigger secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome. Although hypofibrinogenemia is a shared feature of sepsis and hemophagocytic lymphohistiocytosis, there are no data about fibrinogen as a biomarker to identify children with sepsis/secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome overlap. We hypothesized that hypofibrinogenemia is associated with poor outcomes and secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome and has utility as a screening biomarker for this sepsis phenotype.

Design

A retrospective cohort study of patients less than or equal to 21 years treated for severe sepsis from January 2012 to December 2014.

Setting

Emergency department and PICU at a single academic children's hospital.

Patients

Consecutive patients with greater than or equal to one episode of hypofibrinogenemia (serum fibrinogen < 150 mg/dL) within 7 days of sepsis were compared with a random sample of patients without hypofibrinogenemia using an a priori sample size target of 190. Thirty-eight patients with hypofibrinogenemia were compared with 154 without hypofibrinogenemia.

Interventions

None.

Measurements and main results

The primary outcome was "complicated course" (composite of 28-d mortality or ≥ two organ failures at 7 d). Secondary outcomes were 28-day mortality and fulfillment of diagnostic criteria for secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome. We used Wilcoxon rank-sum, Fisher exact test, and multivariable logistic regression to compare patients with versus without hypofibrinogenemia. Patients with hypofibrinogenemia were more likely to have a complicated course (73.7% vs 29.2%; p < 0.001), 28-day mortality (26.3% vs 7.1%, p = 0.002), and meet diagnostic criteria for secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome (21.1% vs 1.3%; p < 0.001). After controlling for confounders, hypofibrinogenemia remained associated with complicated course (adjusted odds ratio, 8.8; 95% CI, 3.5-22.4), mortality (adjusted odds ratio, 6.0; 95% CI, 2.0-18.1), and secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome (adjusted odds ratio, 27.6; 95% CI, 4.4-173).

Conclusions

Hypofibrinogenemia was independently associated with poor outcome and secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome in pediatric sepsis. Measurement of fibrinogen may provide a pragmatic biomarker to identify children with possible sepsis/secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome overlap for whom further diagnostic testing and consideration of adjunctive immunomodulatory therapies should be considered.

Extracorporeal Life Support (ECLS) is rarely used in pediatric trauma patients due to bleeding risk, and the use of ECLS following angioembolization of traumatic hemorrhage has never been reported in a child. We report a case of a 10-year-old boy run over by a parade float resulting in severe thoracic, abdominal, and pelvic trauma, with hemorrhage from pelvic fractures requiring massive transfusion. Due to ongoing blood product requirements and contrast extravasation near the symphysis pubis, angioembolization of the internal iliac arteries was performed. Extreme hypoxemia persisted despite maximal ventilator support due to pulmonary contusions and aspiration pneumonitis. Six hours after angioembolization, venovenous ECLS was initiated. Following an initial heparin bolus, ECLS was run without anticoagulation for 12 h, but development of circuit clot required resumption of low-dose heparin. After four days, his respiratory status improved substantially and ECLS was discontinued. There were no hemorrhagic complications. The patient was discharged home in good health following inpatient rehabilitation. In this case, ECLS was successfully used in the treatment of post-traumatic respiratory failure 6 h following angioembolization of pelvic hemorrhage in a pediatric trauma patient. Further research is needed to determine the safest interval between hemorrhage control and ECLS in severely injured children.