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.