Hepatic failure is a severe condition resulting from various factors that cause significant impairment or decompensation of the liver's synthetic, detoxification, metabolic, and biotransformation functions[10]. This condition primarily manifests as jaundice, coagulation dysfunction, hepatorenal syndrome, hepatic encephalopathy, and ascites[11]. Hepatic failure progresses rapidly, with a high short-term mortality rate, and effective medications and treatments in internal medicine are currently lacking[12].One effective treatment method for hepatic failure is the artificial liver support system (ALSS)[13]. This method utilizes the strong regenerative capacity of hepatocytes and employs an external mechanical, physical, and biological device to remove harmful substances, supplement essential substances, improve the internal environment, and temporarily replace part of the liver's function[14, 15]. This approach creates conditions conducive to hepatocyte regeneration and liver function recovery. The ALSS has emerged as the foremost clinical treatment method for acute-on-chronic liver failure (ACLF) due to its ability to restore liver function, improve patient prognosis, and enhance patients’ quality of life[16].
The Double Plasma Molecular Adsorption System (DPMAS) is a widely used artificial liver model that separates plasma through a plasma separator and sequentially channels it through an anion resin plasma bilirubin adsorption column followed by a neutral macroporous resin adsorption column[4]. DPMAS can not only adsorb bilirubin but also effectively eliminate macromolecular hepatic failure toxins and inflammatory mediators[17, 18]. The extracorporeal circulation pipeline in this model is quite complex, and the adsorption column affects anticoagulants. Therefore, appropriate anticoagulation methods are essential for the successful implementation of DPMAS[15]. These methods include heparin-free anticoagulation, systemic anticoagulation, and regional anticoagulation. However, each method has limitations: heparin-free anticoagulation may increase filter clotting, systemic anticoagulation may exacerbate bleeding, and regional citrate anticoagulation may lead to citrate toxicity[19].
NM is a broad-spectrum and potent serine protease inhibitor that strongly inhibits activated coagulation factors, resulting in anticoagulant effects independent of AT-III. NM exhibits significant inhibitory activity against various plasma proteins, including thrombin, factors XIIa and Xa, kallikrein, complement factors C1r and C1s, as well as trypsin[20, 21]. NM has a very short half-life of approximately 8–10 min and might have positive effects on patients who require coagulation[22]. In a Japanese study involving 2227 patients undergoing blood purification, the treatment methods included CRRT, IHD, and PMX-DHP. The most frequently used anticoagulation method was NM (84.9%), followed by unfractionated heparin (11.5%) and LMWH (2.4%)[23]. NM is a safe and effective anticoagulant for CRRT and allows sufficient filter survival without increasing the risk of bleeding in critically ill patients with AKI and bleeding tendencies[24]. Studies have indicated that the post-filter time-weighted average activated clotting time may serve as an effective predictor of bleeding complications during continuous renal replacement therapy with NM[25]. In addition, some studies have found that the lifespan of CRRT anticoagulant filters is shortened compared to those used with unfractionated heparin[26]. However, since the treatment duration of DPMAS is not long, the use of NM anticoagulation may not significantly impact the treatment.
Currently, there are few reports on the use of NM for DPMAS anticoagulation. This study explored the use of NM for DPMAS. In this study, there was no significant difference in the decrease rate of total bilirubin between the two groups, indicating that the two anticoagulants had no effect on the adequacy of dialysis. In terms of safety, there was no gastrointestinal bleeding in the treatment group, whereas there were two cases of gastrointestinal bleeding in the control group, showing a significant difference. No adverse reactions such as rash, skin itching, fever, palpitations, allergies, or anaphylactic shock occurred in either group. The results suggest that when DPMAS is used to treat hepatic failure, NM anticoagulation is effective and does not result in insufficient anticoagulation. Furthermore, the use of NM anticoagulation is safer, likely due to the short half-life of NM and its removal by dialysis.
This study also has certain limitations. The sample size included in this study is small, and patients with active bleeding were excluded. Due to the short treatment time of DPMAS, the effect of NM on filter lifespan cannot be fully demonstrated. In the future, it is urgent to expand the sample size, improve the assessment of bleeding risk levels before treatment, and further explore the safety and effectiveness of NM anticoagulation in blood purification.