Portal venous blood flow velocity is a factor associated with portal venous thrombosis after partial splenic artery embolization in hepatic cirrhosis patients

Objective: To investigate risk factors for portal venous thrombosis (PVT) after partial splenic artery embolization (PSE) in hepatic cirrhosis patients. Methods: The authors retrospectively analyzed 151 hepatic cirrhosis patients with hypersplenism who underwent partial splenic artery embolization between January 2020 and December 2021. The patients were divided into a PVT group and a non-PVT group according to whether they had PVT after PSE. Univariate analyses were performed to select risk factors for PVT after PSE, and multivariate analysis was used to analyze variates with a value of P less than 0.1 in univariate analysis. Results: There were 151 patients enroled in the study, with 22 patients in the PVT group and 129 patients in the non-PVT group. There was no significant difference in terms of age, sex, smoking, hypertension, diabetes, Child–Pugh between two groups. White blood cell (WBC) and platelet counts after PSE were significantly higher than those before PSE in both the PVT group and non-PVT group. Univariate analysis showed that portal venous blood flow velocity, ligation of oesophageal varices and WBC after PSE were found to have a P value less than 0.1. Multivariate analysis showed that portal venous blood flow velocity was a factor associated with PVT after PSE. Conclusion: Portal venous blood flow velocity was a factor associated with PVT after PSE. Portal venous blood flow velocity should be considered before patients undergo PSE.


Introduction
Hepatic cirrhosis is a widely prevalent disease with both high morbidity and mortality rates.There are many complications of hepatic cirrhosis, and complications are the leading cause of hepatic cirrhosis patient death [1][2][3] .Complications include hepatic encephalopathy, upper gastrointestinal bleeding, ascites, hepatorenal syndrome, spontaneous peritonitis, hepatopulmonary syndrome, portal venous thrombosis (PVT), etc.In addition, hepatic cirrhosis is often accompanied by hypersplenism, whose manifestations are decreased white blood cell (WBC) count, haemoglobin and platelet count.
Partial splenic artery embolization (PSE) is widely used as a treatment for hypersplenism in hepatic cirrhosis patients.Although effective in treating hypersplenism, PSE can cause complications such as PVT, splenic abscess, fever and pain [4][5][6] .Currently, there is few data about the prevalence of PVT following PSE in patients with hepatic cirrhosis.A study conducted by Ogawa et al. [7] found that 9 patients showed appearance or growth of thrombusin all 67 patients who underwent partial splenic artery embolization.The development of PVT is associated with an increased risk of death [8][9][10] .It is important to assess the risk factors for PVT after PSE in hepatic cirrhosis patients.
Studies on risk factors for PVT after PSE have mainly focused on the infarcted splenic volume and Child-Pugh score [4,6,11] .No

Patients
This was a retrospective clinical study approved by the ethics committee of our hospital, the Institutional Review Board no. is TY-ZKY-021-01.The study was conducted in accordance with the Declaration of Helsinki.Informed consent was obtained from all patients.The study was registered.The clinical trial number was ChiCTR2100048291 (https://www.chictr.org.cn/bin/userProject).The work has been reported in line with the STROCSS criteria [12] .Data from hepatic cirrhosis patients with hypersplenism who underwent PSE between January 2017 and December 2021 were collected.The inclusion criteria were as follows: (a) patients diagnosed with hepatic cirrhosis with hypersplenism and (b) patients who received PSE treatment.Exclusion criteria were as follows: (a) patients who had PVT before PSE; (b) patients who did not perform computed tomography (CT) after PSE; and (c) patients with incomplete data.Patients were diagnosed with hepatic cirrhosis by abdominal ultrasound, CT or MRI.Hypersplenism was dignosed if patients had decrease of WBC, haemoglobin and platelet.The patients were divided into a PVT group and a non-PVT group according to whether they had PVT after PSE.Patients were followed up until June 2022 (Figure 1).

PSE procedure
Under local anaesthesia, a 5.0-Fr sheath was inserted into the common femoral artery.The coeliac artery was selected using a 4.0-Fr catheter.A 2.2-Fr microcatheter was coaxially advanced into the splenic artery, and the tip of the catheter was inserted as distally as possible into the splenic artery.Embolization microspheres (500-700 µm, Hengrui Pharmaceutical) were injected slowly, and the embolized area was controlled between 30% and 50%, and was assessed by arteriography at the end of the procedure.Then, gentamicin (80 000 U, Qingfeng Pharmaceutical) and dexamethasone sodium phosphate (10 mg, Tianyao Pharmaceutical) were injected slowly to prevent infection and inflammation.After the procedure, patients were sent back to the ward to rest in bed for 8 hours.

Evaluation items
Before treatment, the following data of all patients were obtained within 24 h after admission: previous history, smoking, drinking, white blood cell (WBC) count, haemoglobin, platelet count, total bilirubin, alanine aminotransferase (ALT), albumin, partial thromboplastin time (PT), activated partial thromboplastin time (APTT), fibrinogen, D-dimer, hepatic encephalopathy, ascites, urea nitrogen, creatinine, heart rate, systolic blood pressure, diastolic blood pressure, PVT, portal venous diameter, and portal venous blood flow velocity.Portal venous diameter, and portal venous blood flow velocity were calculated by Colour Ultrasound at a median of 16 days (range 1-65 days) before PSE.Blood samples were taken for examination of WBCs, haemoglobin and platelets 48-72 h after PSE.Contrast-enhanced CT was performed at a median of 18 days (range, 7-30 days ) to evaluate the presence of PVT after PSE.

Statistical analysis
SPSS 26.0 software was used for analysis.Continuous variables are presented as the mean standard deviation and were analyzed using Students t-test or rank sum test, as appropriate.Categorical variables are presented as frequencies and were assessed using the chi-square test.Univariate analyses were performed to select risk factors for PVT after PSE, and variates with a value of P less than 0.1 were used for multivariate analysis.P less than 0.05 was considered statistically significant.
Comparison of WBCs, haemoglobin and platelets before and after PSE WBC, haemoglobin and platelet counts before and after PSE were compared between the PVT group and non-PVT group.WBC counts after PSE were significantly higher than WBC counts before PSE in both the PVT group (P = 0.005) and the non-PVT group (P = 0.000).There were no significant differences between haemoglobin after PSE and haemoglobin before PSE in either the PVT group or the non-PVT group.Platelets after PSE were significantly higher than WBCs before PSE in both the PVT group (P = 0.018) and the non-PVT group (P = 0.000) (Table 2).

Comparison of variates between the PVT group and the non-PVT group
There were more patients who had ligation of oesophageal varices in the PVT group than in the non-PVT group (P = 0.010) .WBC after PSE (P = 0.036) and portal venous blood flow velocity (P = 0.001) were higher in the non-PVT group than in the PVT group.There was no significant difference between the PVT group and the non-PVT group in variates, such as, age, sex, smoking, hypertension, diabetes, Child-Pugh, WBC etc. (Table 3).

Univariate analysis of factors associated with PVT after PSE
Univariate analysis was performed to assess the risk factors.Portal venous blood flow velocity (P = 0.004) was found to be associated with PVT after PSE, and patients with higher portal venous blood flow velocity were less likely to have PVT after PSE.Ligation of oesophageal varices (P = 0.074) and WBC (P = 0.065) after PSE were found to have a P value less than 0.1 (Table 4).Risk factors with a P value less than 0.1 in univariate analysis were included in multivariate analysis.The results showed that portal venous blood flow velocity was associated with PVT after PSE (P = 0.004) (Table 5).

Discussion
PVT is a complication of not only hepatic cirrhosis but also PSE.Hepatic cirrhosis patients with PVT are at high risk of mortality [8,9] .As PSE is a frequently used treatment for hypersplenism in hepatic cirrhosis patients, it is of great significance to identify factors associated with PVT after PSE.PSE and splenectomy are two main treatments for hypersplenism, but patients are more willing to accept PSE because PSE is an effective method with minimal trauma.In this study, PSE was successful in elevating patients' WBC and platelet counts.
Several studies have been performed to assess risk factors for PVT after splenectomy.Preoperative splenic vein diameter is a risk factor for postsplenectomy PVT [13,14] .Kuroki speculated that stagnation of blood flow in the splenic vein may be associated with PVT after splenectomy [15] .In this study, results showed that portal venous blood flow velocity was a factor associated with PVT after PSE.Patients with higher portal venous blood flow velocity were less likely to have PVT after PSE, whereas patients with lower portal venous blood flow velocity were more likely to have PVT, which was the same as what Kuroki had speculated.
Several studies have reported that splenic infarction percentages and splenic infarction volume are associated with PVT [4,6,7,15] .Zhu et al. [16] reported that a percentage of infarcted spleen greater than 70% could significantly increase the likelihood of PVT.However, in this study, the percentage of infarcted spleen in all patients was controlled roughly within 30-50%, so the percentage of infarcted spleen was not assessed as a risk factor.
Ogawa et al. [7] reported that a large maximum diameter of the portal venous system was a risk factor for PVT.In this study, the diameter of the portal venous system was slightly larger in the PVT group than in the non-PVT group, but there was no significant difference between the two groups.There were some differences between our study and Satoyuki Ogawa's study.In our study, patients with PVT before PSE were excluded.Satoyuki Ogawa did not exclude patients with PVT before PSE; for those patients with PVT before PSE, thrombus growth was assessed.This might explain why the diameter of the portal venous system was not a risk factor for PVT, as reported by Satoyuki Ogawa.
There were some limitations of the present study.First, this was a single-centre retrospective study, and the number of patients with PVT after PSE was small.A multicenter prospective study with more patients is needed to validate the results.Second, the duration of colour ultrasound before PSE and assessment of PVT after PSE was not constant.Third, although PVT was a complication of PSE, no patients were treated with anticoagulation therapy before and after PSE, and we did not investigate whether patients benefited from anticoagulation therapy.It would be meaningful to investigate whether patients with a high risk of PVT after PSE need anticoagulation therapy.
In conclusion, portal venous blood flow velocity was a factor associated with PVT after PSE, and patients with higher portal venous blood flow velocity were less likely to have PVT after PSE, whereas patients with lower portal venous blood flow velocity were more likely to have PVT.Portal venous blood flow velocity should be considered before patients undergo PSE.
Portal venous blood flow velocity should be considered before patients undergo PSE.studies have described portal venous blood flow velocity as a risk factor for PVT after PSE.The purpose of this study was to investigate the relationship between portal venous blood flow velocity and PVT after PSE in hepatic cirrhosis patients.
HIGHLIGHTS• The study investigated risk factors for portal venous thrombosis (PVT) after partial splenic artery embolization (PSE) in hepatic cirrhosis patients.• Multivariate analysis showed that portal venous blood flow velocity was a factor associated with PVT after PSE.• Portal venous blood flow velocity was a factor associated with PVT after PSE.•

Table 2
Comparison of WBC, haemoglobin and platelet before and after PSE PSE, partial splenic artery embolization; PVT, portal venous thrombosis; WBC, white blood cell.

Table 3
Comparison of variates between PVT group and non-PVT group ALT, alanine aminotransferase; APTT, activated partial thromboplastin time; PSE, partial splenic artery embolization; PT, partial thromboplastin time; PVT, portal venous thrombosis; WBC, white blood cell.

Table 4
Univariate analysis of risk factors for PVT after PSE