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.