Contributions
Abstract: PB1812
Type: Publication Only
Background
Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome evolving from a pathologic immune response, leading to uncontrolled cytokine release and organ damage. In adults, HLH can be triggered by various conditions like infections, malignancies, or autoimmune diseases. HLH treatment is based on immunosuppression and trigger directed therapies. However, despite improved treatment protocols, patients with severe HLH still have a poor prognosis. Cytokine adsorbing devices are increasingly used in treating critically ill patients with inflammation and hypercytokinemia to prevent and reduce the effects of pro-inflammatory cytokines1. Thus, cytokine adsorption may be a suitable therapeutic option in severe, life-threatening HLH.
Aims
We report the case of a 49-year old male patient presenting with severe coagulation abnormalities due to hemophagocytic lymphohistiocytosis.
Methods
Case report
A 49-year old male patient was admitted to intensive care unit (ICU) because of suspected sepsis. A prodromal two week episode had led to previous emergency room admissions due to fever of unknown origin (FUO). We began fluid replacement therapy and started empiric antibiotic treatment with piperacillin/tazobactam, leading to initial improvement of the patients´ clinical condition. However, pancytopenia progressed and coagulation parameters deteriorated to unmeasurable levels (fibrinogen 0.31 g/l [reference range 1.8 - 3.5], INR > 8) making large scale substitution treatment necessary. Despite extensive diagnostics, no infectious focus was found. Indicated by markedly elevated ferritin values (81,393 µg/l), HLH was diagnosed with 7 of 8 HLH-2004 criteria. A combination therapy using dexamethasone, polyvalent immunoglobulins and etoposide was administered without improvement of coagulation parameters. Due to progressive multiple organ failure (respiratory/renal/hepatic/hematopoietic) we initiated cytokine adsorption using Cytosorb columns in serial application with continuous hemofiltration. In marked association with cytokine adsorption, coagulation features significantly improved and inflammatory markers decreased. Multiple organ failure reversed and the patient was moved to the general ward.
Results
Overall, hemoadsorptive treatment was performed over 12 days. Cytokine adsorption resulted in a substantial decline of C-reactive protein and interleukin-6. Using immunosuppression and hemoadsorption, coagulation slowly improved. Moreover, ferritin and lactate dehydrogenase levels decreased, whereas no effect on soluble interleukin-2 levels was observed. Utilization of the cytokine adsorber was safe and well-tolerated, and no relevant side effects were noticed. No HLH-triggering disease was identified. Functional tests including degranulation assays and perforin expression were within normal range. Currently, the patient is in follow-up one year after initial HLH diagnosis with tapered immunosuppressive treatment.
Conclusion
HLH treatment remains challenging as multiple organ systems can be affected. Besides immunosuppression and trigger specific therapies, cytokine adsorption is a useful tool in imminent or present multiple organ failure, when drug treatment intensification is limited by organ function.
1. Friesecke S, Trager K, Schittek GA, Molnar Z, Bach F, Kogelmann K, et al. International registry on the use of the CyoSorb(R) adsorber in ICU patients: Study protocol and preliminary results. Med Klin Intensivmed Notfmed 2017 Sep. 4.
Session topic: 34. Bleeding disorders (congenital and acquired)
Keyword(s): Coagulation, Cytokine, Ferritin, T cell activation
Abstract: PB1812
Type: Publication Only
Background
Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome evolving from a pathologic immune response, leading to uncontrolled cytokine release and organ damage. In adults, HLH can be triggered by various conditions like infections, malignancies, or autoimmune diseases. HLH treatment is based on immunosuppression and trigger directed therapies. However, despite improved treatment protocols, patients with severe HLH still have a poor prognosis. Cytokine adsorbing devices are increasingly used in treating critically ill patients with inflammation and hypercytokinemia to prevent and reduce the effects of pro-inflammatory cytokines1. Thus, cytokine adsorption may be a suitable therapeutic option in severe, life-threatening HLH.
Aims
We report the case of a 49-year old male patient presenting with severe coagulation abnormalities due to hemophagocytic lymphohistiocytosis.
Methods
Case report
A 49-year old male patient was admitted to intensive care unit (ICU) because of suspected sepsis. A prodromal two week episode had led to previous emergency room admissions due to fever of unknown origin (FUO). We began fluid replacement therapy and started empiric antibiotic treatment with piperacillin/tazobactam, leading to initial improvement of the patients´ clinical condition. However, pancytopenia progressed and coagulation parameters deteriorated to unmeasurable levels (fibrinogen 0.31 g/l [reference range 1.8 - 3.5], INR > 8) making large scale substitution treatment necessary. Despite extensive diagnostics, no infectious focus was found. Indicated by markedly elevated ferritin values (81,393 µg/l), HLH was diagnosed with 7 of 8 HLH-2004 criteria. A combination therapy using dexamethasone, polyvalent immunoglobulins and etoposide was administered without improvement of coagulation parameters. Due to progressive multiple organ failure (respiratory/renal/hepatic/hematopoietic) we initiated cytokine adsorption using Cytosorb columns in serial application with continuous hemofiltration. In marked association with cytokine adsorption, coagulation features significantly improved and inflammatory markers decreased. Multiple organ failure reversed and the patient was moved to the general ward.
Results
Overall, hemoadsorptive treatment was performed over 12 days. Cytokine adsorption resulted in a substantial decline of C-reactive protein and interleukin-6. Using immunosuppression and hemoadsorption, coagulation slowly improved. Moreover, ferritin and lactate dehydrogenase levels decreased, whereas no effect on soluble interleukin-2 levels was observed. Utilization of the cytokine adsorber was safe and well-tolerated, and no relevant side effects were noticed. No HLH-triggering disease was identified. Functional tests including degranulation assays and perforin expression were within normal range. Currently, the patient is in follow-up one year after initial HLH diagnosis with tapered immunosuppressive treatment.
Conclusion
HLH treatment remains challenging as multiple organ systems can be affected. Besides immunosuppression and trigger specific therapies, cytokine adsorption is a useful tool in imminent or present multiple organ failure, when drug treatment intensification is limited by organ function.
1. Friesecke S, Trager K, Schittek GA, Molnar Z, Bach F, Kogelmann K, et al. International registry on the use of the CyoSorb(R) adsorber in ICU patients: Study protocol and preliminary results. Med Klin Intensivmed Notfmed 2017 Sep. 4.
Session topic: 34. Bleeding disorders (congenital and acquired)
Keyword(s): Coagulation, Cytokine, Ferritin, T cell activation