2.1 Case 1
A 4-year-old male was admitted to hospital due to diarrhea and seizure
caused by unknown pathogen. He received antibiotic (meropenem) and
anticonvulsive treatment (carbamazepine) for two days. However, the
patient presented hyperpyrexia, erythra and multiple organ dysfunction
syndrome with coagulopathy (INR 5.46, APTT 108s), respiratory
insufficiency, and hypotension. He was subsequently transferred to
pediatric intensive care unit (PICU). With regard to the erythra and
fever secondary to antiepileptic drug (carbamazepine), antiepileptic
Drug-Induced Hypersensitivity Syndrome was diagnosed. The patient
suffered from hemoglobinopenia, thrombopenia, hepatosplenomegaly,
hyperferritinemia (ferritin 726.9 ng/ml, normal range 11.0-306.8 ng/mL),
hypofibrinogenemia (fibrinogen 0.60 g/L, normal range 1.50-4.35 g/l),
hypertriglyceridemia (triglycerides 4.2 mmol/L, normal range 0.4-1.8
mmol/L) and low NK cell activity (2.06 %, normal range 5-26 %) (Table
1). Five of eight diagnostic criteria were found to be fulfilled, and
the patient was diagnosed with HLH based on HLH-2004 guideline. Bone
marrow biopsy showed a high number of activated macrophages that
incorporated erythrocytes and granulocytes, and the diagnosis of HLH was
confirmed. Gene examination was performed to identify the primary HLH.
Carbamazepine was out of use, dexamethasone and norepinephrine was
administrated.
White blood cell (WBC) (40.8 ×109/L, normal range
3.5-9.5 ×109/L) and procalcitonin (PCT) (>100 ng/ml,
normal range 0-0.05 ng/ml) were significantly elevated. In addition,
damage of liver function occurred with a highly increased in
transaminases (Table 1). Sonography of the abdomen showed formerly
detected hepatosplenomegaly but regular portal vein and hepatic vein
flow in Doppler. Multiple blood and urine cultures as well as virus
polymerase chain reaction (PCR) for Epstein-Barr virus (EBV) and
cytomegalovirus (CMV) were negative. X-ray of the thorax was remarkable
and showed no signs of infection. Continuous therapy with meropenem did
not improve circulatory dysfunction or laboratory parameters of
inflammation.
In view of largely increased interleukin (IL)-6 (1467.6 pg/ml, normal
range 0-7 pg/ml) and ferritin (726.9 ng/ml) as well as the diagnosis of
acute kidney injury, plasma exchange (PE) and
continuous veno-venous
hemodiafiltration (CVVHDF) were considered to start. However, during
that period, plasma separator was scared and unavailable for us because
of coronavirus disease 2019 (COVID-19) epidemic. Therefore we tried to
use the hemoadsorption combined with CVVHDF. A hemoadsorption cartridge
(HA330-II perfusion column, Zhuhai Health Sails Biotechnology Co.,Ltd.,
Zhuhai, China) was integrated into the extracorporeal circuit to promote
cytokine adsorption. The hemoadsorption treatment lasted for 3 hours
every time and then the HA330-II perfusion column was moved off from the
hemodiafiltration circuit. Hemoadsorption was performed once a day and
totally for three times. CVVHDF (substitute flow 20 mL/kg.h, dialysate
flow 20 mL/kg.h and blood flow 3-5mL/kg.min) lasted for about 72 hours
and the filter was changed when it was considered clotted.
Anticoagulation was performed with heparin sodium. After 72 hours of
treatment, the concentration of IL-6 and ferritin separately fall to
119.25 pg/ml and 295.3 ng/ml (Figure 1). The norepinephrine (NE) (0.1
µg/kg/min) could be wean off as well as erythra alleviated
significantly. However, fever and erythra recurrenced 48 hours after the
cease of CVVHDF and hemoadsorption. So single hemoadsorption (HA330-II
perfusion column, duration of 3 hours) by perfusion machine was
performed three times (once a day) again. Subsequently, no further
deterioration of the patient’s clinical condition was seen. Gene
examination exclude the primary HLH. The patient was discharged from
PICU on day 10 and at that time his PCT level declined from more than
100 ng/ml to 0.12 ng/ml.