Pediatric liver transplantation is an important part of clinical liver transplantation for children suffering from end-stage liver disease[13]. Recently, data promulgated by a Japanese research team showed that the graft survival rates were 90.5%, 90.4%, 84.6%, 82.0%, 79.9% 1, 5, 10, and 20 years after surgery, respectively[14]. It was the largest cohort study and followed a total of 2085 children worldwide to observe the overall survival in children with biliary atresia after liver transplantation. The results showed that the postoperative survival rate had improved substantially. However, there are still a series of complications after surgery that affect quality of life. Bleeding and coagulopathy are critical issues complicating pediatric liver transplantation and contributing to morbidity and mortality in cirrhotic children. Vascular complications are common in pediatric liver transplantation[15]. In fact, thrombosis remains the primary cause of early graft failure and retransplantation within the first 30 d after surgery, and it occurs despite prolongation of standard coagulation assays[4]. Vessel anastomosis between the donor and recipient is more difficult because the blood vessels do not match well and the blood vessels of children are thinner than adults[16, 17]. The blood flow signal at the anastomosis of the liver vessel tends to be abnormal after operation, which may cause serious complications such as thrombosis. Perioperative coagulation should not be overcorrected; otherwise, thrombosis can easily develop during and after surgery. Thus, it is important to correct coagulation function accurately. This study found that perioperative coagulation affected the occurrence of postoperative liver blood flow signals. The most common vascular complication after surgery was thrombosis. Sonoclot analyzers can be used to monitor coagulation function in pediatric liver transplantation. After ischemia-reperfusion, the Sonoclot parameter ACT was a risk factor for postoperative thrombosis. It was recommended that ACT be maintained above 228.5 s 1 h after ischemia-reperfusion until the end of surgery to reduce the incidence of abnormal postoperative blood flow.
The liver is a site of synthesis for most coagulation factors and anticoagulant substances. The special pathophysiological changes in liver transplantation lead to a large change in perioperative coagulation function. Children with biliary atresia develop cirrhosis before surgery, affecting the synthesis and release of coagulation factors. Clotting factor production is significantly reduced in the perioperative period anhepatic phase. The release of toxic substances that accumulate from the lower part of the body and perfuse the donor liver after ischemia-reperfusion causes a large blow to the neohepatic stage liver[10, 18]. Liver coagulation function drops again. The coagulation function of the body in the neohepatic stage is the worst. We call this phenomenon the “heparin-like effect”[19]. According to clinical practice, the donor liver was not exposed to heparin in the related liver transplantation, so the coagulation function tended to be stable from 1 h after reperfusion to the end of the operation. During the anhepatic phase and after ischemia-reperfusion, it is necessary to actively and accurately correct blood coagulation to prevent surgical bleeding and excessive correction of coagulation, which can lead to blood stasis and thrombosis[20].
In fact, thrombosis remains the primary cause of early graft failure and retransplantation within the first 30 d following surgery, and it occurs despite prolongation of standard coagulation assays. Hepatic artery thrombosis is the most common vascular complication after liver transplantation, with an incidence of 6%-15%, of which 22.7% require secondary liver transplantation[21, 22]. The portal vein thrombosis rate is 4%-10%, easily leading to portal hypertension[4]. In our study, the incidence rate of patients with thrombosis after surgery was 19%. Among them, 11.5% had abnormal arterial signals and 7.5% had abnormal venous signals. We regarded the patients with abnormal blood flow signals including fast or slow blood flow in the anastomosis or whole blood vessels as thrombosis group. Because patients with these abnormal blood flow signals were likely to eventually form irreversible thrombosis. There are many reasons for the incidence of thrombosis, among which anastomotic stenosis and hypercoagulability are important factors[23]. Thus, hypercoagulability during liver transplantation deserves a closer look as thromboembolic events are associated with high morbidity and mortality rates[24].
There are many methods for monitoring coagulation function, including traditional detection of PT, INR, APTT, etc. Some equipment, such as TEG (thromboelastography) and Sonoclot coagulation analyzers have been widely used clinically, especially in heart surgery and transplant surgery[25–27]. However, the value of these traditional parameters, such as PT and APTT, has been questioned in the acute perioperative setting because of the delay between blood sampling and obtaining the results. Additionally, these tests are carried out on plasma rather than whole blood, and they do not provide much information about platelet function[28]. Currently, TEG is widely used in major operations, such as heart surgery and adult liver transplant, because it contains many parameters for accurately monitoring the coagulation system. However, TEG requires specialized personnel and has a high cost. The most important thing is that both traditional detection methods and TEG detection take a long time to obtain results and cannot provide monitoring in real time[29]. The environmental changes during the perioperative period of liver transplantation are faster. Therefore, real-time monitoring is required for proper coagulation adjustment. The Sonoclot analyzer is a point-of-care coagulation monitoring system that can immediately observe the patient's coagulation function, such as clotting factor levels, Fib levels, and PF changes. The advantages Sonoclot devices show are that the blood is analyzed at the bedside, allowing a faster turnaround time, and the coagulation status is assessed on whole blood, which is more meaningful than a single index and is an effective means of detecting platelet function[30]. Sonoclot devices are used in situations of abnormal coagulation, such as cardiac and liver transplant surgery[8]. Sonoclot analyzers monitor three basic parameters: ACT (the reference value is 119–195 s, and the clinical reference significance is greater), CR (the reference value is 7–23) and PF (the reference value is 1.5–4.5)[30]. Our study proved that Sonoclot devices could be used to guide the monitoring of coagulation function during the perioperative liver transplantation period in children. The most meaningful parameter was ACT. The value of ACT was lower in the thrombosis group, but there were no significant differences in CR and PF between the two groups. These results were consistent with clinical findings. Generally, we infuse fresh frozen plasma with no infusion of fibrinogen, platelets, etc.
It is very necessary to maintain a state of lower coagulation than normal for pediatric related-living donor liver transplantation due to special physiological and pathological changes and anatomical features. Therefore, the appropriate coagulation parameters according to Sonoclot devices have always been the focus of our research. Under normal circumstances, the Sonoclot analyzer shows that the ACT is 115–195 s. However, in our study, the ACT was maintained at a higher range to reduce postoperative thrombosis. In this experiment, the ROC curve was used to analyze the ACT cutoff value and found that it was better to maintain the ACT above 228.5 s to reduce the occurrence of abnormal blood flow signals. This cutoff value exceeded the standard ACT value of the Sonoclot machine (119–195 s), and the area under the curve (AUC) was higher than 0.9. The diagnostic effect and reliability were higher. However, we found that the number of postoperative bleeding cases was small. There was no relationship between the intraoperative Sonoclot parameters and postoperative bleeding complications. Therefore, we did not explore the maximum ACT that caused bleeding complications after surgery. In our center, we maintain the ACT below 300 empirically, and no related intraoperative and postoperative excessive bleeding occurs. Of course, this needs further exploration.
Undeniably, our study had several limitations. First, our study was based on data from a single center. In the future, multicenter research should be performed to verify the accuracy of the ACT value. In addition, we only analyzed the range of Sonoclot parameters that affected postoperative thrombosis, while the cutoff value for Sonoclot parameters that affect postoperative bleeding were not studied.