3 DISCUSSION
The main pathophysiologic feature of HLH is excessive activation and expansion of T lymphocytes (mainly cytotoxic CD8+ T cells) and macrophages. These activated immune cells produce large amounts of pro-inflammatory cytokines, creating hypercytokinemia/hyper- inflammation and subsequent multiple organ failure 5. Patients with severe HLH present high levels of cytokines such as IL-1, IL-2, IL-6, IL-18, tumor necrosis factor (TNF)-α, interferon (IFN)-γ. Among these cytokines, IL-6 plays a major role in HLH and appear a good target molecule for a cytokine storm. Excessive expression of IL-6 leads to the excessive activation and expansion of CD8+T cells and macrophages. It results in acute severe systemic inflammatory response known as ‘cytokine storm’ and can activate the coagulation pathway and vascular endothelial6.
Since HLH can be rapidly fatal without specific intervention, it is recommended that treatment should be started when there is a high clinical suspicion, even when results of diagnostic studies are still pending. Except for EBV-driven HLH, there are no specific treatment guidelines for HLH secondary to infections. Conventionally, in addition to the management of infection, immunoglobulins and methylprednisolone were administered to attenuate inflammation, which could only reduce the production of cytokines rather than remove any cytokines that had been caused 7.
Several studies have demonstrated the use of blood purification for patients with HLH. DiCarlo et al 8 reported that hemofiltration when properly applied could relieve severe metabolic acidosis and reduce the level of cytokine activity with multiple organ dysfunction syndrome (MODS). High volume hemofiltration (HVHF) was used by Cui Y et al 9 to reduce cytokines levels and restore organ function. Demirkol et al 10 reported that patients with secondary hemophagocytic syndrome can be successfully treated with PE, IVIG, and methylprednisolone. Additionally, hemoadsorption by CytoSorbTM column 11 or endotoxin-binding polymyxin-B- immobilized fiber column12 was tried for the treatment of HLH in a few researches.
For HLH patients, we used to carry out PE as the adjuvant treatment to control the hypercytokinemia. When the patients complicated with multi-organ dysfunction, CVVHD(F) was combined with PE. PE can efficiently remove big molecule such as pathogenic cytokines and toxic substances 13, 14. However, PE is often limited due to an inadequate plasma supply 15 and can carry transfusion-related risks. The two cases met the lack of plasma separator. So we tried the new combination to create a unique treatment, combined hemoadsorption therapy by HA330-II perfusion column (Zhuhai Health Sails Biotechnology Co.,Ltd., Zhuhai, China) with CVVHDF. HA330-II perfusion column is a macroporous resin hemoperfusion device which remove cytokines via small polymer beads. Originally, HA330-II perfusion column was reported as one part of DPMAS and successfully used in liver failure patients 16, 17. It can effectively reduce inflammatory cytokine. Combined CVVHDF with HA330-II perfusion column could not only reduce the total amount of blood needed for PE, but obtained some very good curative effect.
As far as we know, this is the first case series report involving the clinical application of HA 330-II perfusion column in children suffering from HLH. In two cases we reported, high level of IL-6 was decreased to normal after treatment of the hemoadsorption combined with CVVHDF. As inflammatory cytokine level had returned to normal, patients’ signs and symptom fade away. In a word, the marked decrease in IL-6 plasma levels, decrease of inflammatory cytokines and stabilization of liver function were observed after treatment, which proved the efficiency of HA330-II perfusion column. Importantly, treatment was safe and well-tolerated, without any adverse events.
In conclusion, hemoadsorption by HA330-II column is safe and ffective in HLH patients. A limitation of this study was that the number of cases was too small. Further studied need to do in the future.