Introduction: The “Hepatology Digest – Liver Vascular Disease Column” is an academic column initiated by Dr. Qixing Shun from the Department of Gastroenterology, Northern Theater General Hospital, in response to the invitation of the editorial department of “Hepatology Digest”. It regularly collects and organizes research progress in the field of hepatic vascular diseases. Every two weeks (Wednesday), an important literature is selected for in-depth discussion, aiming to help readers understand the rationale behind clinical research, inspiring clinical and scientific thinking.
- Article Summary
Splanchnic vein thrombosis (SVT) is a severe vascular complication of acute pancreatitis (Easler J, et al. Clin Gastroenterol Hepatol. 2014;12(5):854‐862; Jiang W, et al. World J Gastroenterol. 2014;20(44):16698‐16701.). The incidence of SVT associated with acute pancreatitis can reach 16.6% to 22.6% (Xu W, et al. Gastroenterol Res Pract. 2015;2015: 245460; Butler JR, et al. HPB (Oxford). 2011;13(12):839‐845.). Variations in incidence among studies are related to the severity of acute pancreatitis and differences in imaging diagnostic methods. SVT associated with acute pancreatitis can affect the portal vein (PV), splenic vein (SV), and superior mesenteric vein (SMV) (Jiang W, et al. World J Gastroenterol. 2014;20(44):16698‐16701; Nawacki Ł, et al. Clin Appl Thromb Hemost. 2021;27:10760296211010260.). In patients with acute pancreatitis, SVT is mainly associated with local inflammatory reactions and enlargement of the pancreas or pseudocysts (Nadkarni NA, et al. Pancreas. 2013;42(6):924‐931; Rebours V, et al. Am J Gastroenterol. 2012;107(10):1579‐1585.). SVT typically occurs within 1 to 2 weeks of onset in moderate to severe acute pancreatitis and can prolong the course and increase mortality. In most patients, SVT is usually asymptomatic, but when SMV obstruction occurs, it can lead to intestinal ischemia. Regional portal hypertension can lead to the development of portal cavernoma and esophagogastric variceal bleeding (Harris S, et al. Pancreas. 2013;42(8):1251‐1254.).
The effective management strategy for acute pancreatitis-related SVT is still controversial (Pancreas Study Group, Chinese Society of Gastroenterology, Chinese Medical Association. J Dig Dis. 2021;22(1):2-8.). The latest clinical guidelines in China suggest the use of anticoagulant therapy when SVT involves SMV and abdominal symptoms related to intestinal ischemia occur (Duran M, et al. World J Emerg Surg. 2015;10:45.). This recommendation is primarily based on the adverse effects of symptomatic SVT on patient outcomes (Anis FS, et al. J Gastroenterol Hepatol. 2022;37(3):446-454.).
A study by Yin et al., published in July 2023 in the journal “Clinical and Applied Thrombosis-Hemostasis,” conducted a systematic review and meta-analysis to investigate the differences in SVT recanalization, bleeding, death, intestinal ischemia, portal cavernoma, esophagogastric variceal bleeding, major bleeding, and gastrointestinal bleeding between patients with acute pancreatitis-related SVT who received anticoagulant therapy and those who did not.
The systematic review included 14 retrospective cohort studies and 2 prospective cohort studies identified through searches in PubMed, EMBASE, and the Cochrane Library databases until July 14, 2022. The results showed that after receiving anticoagulant therapy, the incidence rates of SVT recanalization, bleeding for any reason, death, intestinal ischemia, portal cavernoma, and esophagogastric variceal bleeding were 44.3%, 10.7%, 13.3%, 16.8%, 21.2%, and 29.1%, respectively. Anticoagulant therapy significantly increased the rate of SVT recanalization but also posed a potential risk of bleeding. Additionally, there were no significant differences in mortality, intestinal ischemia, portal cavernoma, and esophagogastric variceal bleeding between patients with acute pancreatitis-related SVT who received anticoagulant therapy and those who did not.
In conclusion, anticoagulant therapy may be effective in promoting SVT recanalization in acute pancreatitis-related SVT, but it does not seem to improve overall survival.
- Key Research Results Analysis and Clinical Significance
- Included Studies and Patient Characteristics:
A total of 16 studies were included, encompassing 698 cases of acute pancreatitis-related splanchnic vein thrombosis (SVT). Among these studies, 9 were published in full-text form, and 7 were in abstract form. Geographically, 6 studies originated from Europe, 2 from Asia, and 8 from North America. Quality-wise, 5 studies were classified as high-quality, and 11 as moderate-quality.
Seven studies reported the severity of acute pancreatitis. Among them, there were 50 cases (14.6%) of mild acute pancreatitis, 93 cases (27.2%) of moderately severe acute pancreatitis, and 199 cases (58.2%) of severe acute pancreatitis. All 16 studies provided information on the sites affected by SVT. Specifically, in 306 cases of acute pancreatitis, SVT only affected the splenic vein (SV), in 87 cases it affected only the portal vein (PV), in 82 cases it involved PV+SV+SMV, in 55 cases it involved PV+SV, in 38 cases it involved PV+SMV, in 29 cases it involved SV+SMV, and in 19 cases it only affected SMV.
Two studies mentioned the timing of anticoagulant drug use. One study suggested using anticoagulant drugs when symptoms related to intestinal ischemia and/or hepatic decompensation occurred, while another study recommended initiating anticoagulant therapy on the day of acute pancreatitis diagnosis.
Seven studies provided detailed information on the types and doses of anticoagulant drugs used.
2. Recanalization
Twelve studies reported the thrombus recanalization rates in patients with acute pancreatitis-related splanchnic vein thrombosis (SVT). Among SVT patients receiving anticoagulant treatment and those not receiving it, the combined thrombus recanalization rates were 44.3% [95% confidence interval (CI): 32.3%–56.6%] and 20.6% (95% CI: 14.0%–28.2%), respectively. The thrombus recanalization rate in SVT patients receiving anticoagulant treatment was significantly higher than in those not receiving it (relative risk (RR) = 1.69, 95% CI: 1.29–2.19, P < 0.01). There was no significant heterogeneity among the studies (I² = 0%, P = 0.56).
Subgroup analysis showed that in studies of moderate quality (43.1% vs. 20.3%, RR = 1.72, P < 0.01), retrospective studies (44.8% vs. 20.2%, RR = 1.76, P < 0.01), studies published in full-text form (51.9% vs. 23.1%, RR = 1.86, P < 0.01), abstract form (33.8% vs. 18.3%, RR = 1.80, P = 0.03), studies without intestinal ischemia as an indication for anticoagulant drug use (42.4% vs. 19.1%, RR = 1.74, P < 0.01), studies with a sample size >40 (35.3% vs. 19.7%, RR = 1.67, P < 0.01), and studies with a sample size ≤40 (55.7% vs. 23.0%, RR = 2.25, P < 0.01), SVT patients receiving anticoagulant treatment had a significantly higher thrombus recanalization rate than those not receiving anticoagulant treatment. There was no significant interaction between subgroups. Meta-regression analysis showed a significant publication bias among the studies (P = 0.07).
3. Any Bleeding
Twelve studies reported the incidence of bleeding for any reason in patients with acute pancreatitis-related splanchnic vein thrombosis (SVT). Among SVT patients receiving anticoagulant treatment and those not receiving it, the combined incidence rate of bleeding for any reason was 10.7% (95% CI: 4.9%–18.5%) and 5.7% (95% CI: 2.0%–11.1%), respectively. There was no significant difference in the incidence of bleeding for any reason between the two groups (relative risk (RR) = 1.98, 95% CI: 0.93–4.22, P = 0.07). There was no significant heterogeneity among the studies (I² = 26.2%, P = 0.22).
Subgroup analysis showed that in studies of moderate quality (9.1% vs. 3.1%, RR = 2.46, P < 0.01), and studies with a sample size >40 (15.1% vs. 7.1%, RR = 2.46, P < 0.01), the incidence of bleeding for any reason in SVT patients receiving anticoagulant treatment was significantly higher than in those not receiving anticoagulant treatment. There was no significant interaction between subgroups. Meta-regression analysis showed no significant publication bias among the studies (P = 0.69).
4. Death
Eight studies reported the mortality rate in patients with acute pancreatitis-related splanchnic vein thrombosis (SVT). Among SVT patients receiving anticoagulant treatment and those not receiving it, the combined mortality rates were 13.3% (95% CI: 6.9%–21.4%) and 8.0% (95% CI: 2.8%–15.5%), respectively. There was no significant difference in mortality rates between the two groups (relative risk (RR) = 1.42, 95% CI: 0.62–3.25, P = 0.40). There was no significant heterogeneity among the studies (I² = 33.9%, P = 0.18).
Subgroup analysis showed that in studies published in abstract form (20.3% vs. 3.5%, RR = 3.37, P = 0.02), SVT patients receiving anticoagulant treatment had a significantly higher mortality rate than those not receiving anticoagulant treatment. There was a significant interaction between subgroups based on the publication type of the studies. Meta-regression analysis showed no significant publication bias among the studies (P = 0.85).
5. Intestinal Ischemia
Three studies reported the incidence of intestinal ischemia in patients with acute pancreatitis-related SVT. Among SVT patients receiving anticoagulant treatment and those not receiving it, the combined incidence rates of intestinal ischemia were 16.8% (95% CI: 6.9%–29.9%) and 4.0% (95% CI: 0.1%–17.1%), respectively. There was no significant difference in the incidence of intestinal ischemia between the two groups (RR = 2.55, 95% CI: 0.23–28.16, P = 0.45). There was significant heterogeneity among the studies (I² = 50.4%, P = 0.13). Sensitivity analysis results showed that the heterogeneity among the studies might be derived from the study by Hall et al.
Subgroup analysis showed that in studies of high quality (22.4% vs. 1.2%, RR = 8.54, P = 0.04), SVT patients receiving anticoagulant treatment had a significantly higher incidence of intestinal ischemia than those not receiving anticoagulant treatment. There was a significant interaction between subgroups based on the quality of the studies. Meta-regression analysis showed no significant publication bias among the studies (P = 0.58).
6. Portal Vein Splanchnic Venous Transformation
Four studies reported the incidence of portal vein splanchnic venous transformation (PHVT) in patients with acute pancreatitis-related splanchnic vein thrombosis (SVT). Among SVT patients receiving anticoagulant treatment and those not receiving it, the combined incidence rates of PHVT were 21.2% (95% CI: 7.5%–39.5%) and 34.2% (95% CI: 9.8%–64.2%), respectively. There was no significant difference in the incidence of PHVT between the two groups (RR = 0.51, 95% CI: 0.21–1.22, P = 0.13). There was no significant heterogeneity among the studies (I² = 33.7%, P = 0.21).
Subgroup analysis showed that in studies of medium quality (11.3% vs. 47.6%, RR = 0.33, P < 0.01) and studies with a sample size >40 (23.08% vs. 67.57%, RR = 0.34, P < 0.01), SVT patients receiving anticoagulant treatment had a significantly higher incidence of PHVT than those not receiving anticoagulant treatment. There was no significant interaction between subgroups. Meta-regression analysis showed no significant publication bias among the studies (P = 0.48).
7. Esophagogastric Varices
Three studies reported the incidence of esophagogastric varices in patients with acute pancreatitis-related SVT. Among SVT patients receiving anticoagulant treatment and those not receiving it, the combined incidence rates of esophagogastric varices were 29.1% (95% CI: 16.1%–44.1%) and 33.4% (95% CI: 10.3%–61.9%), respectively. There was no significant difference in the incidence of esophagogastric varices between the two groups (RR = 0.71, 95% CI: 0.38–1.32, P = 0.28). There was no significant heterogeneity among the studies (I² = 0%, P = 0.81).
In subgroup analyses based on study design, study quality, sample size, and anticoagulant treatment indications, anticoagulant treatment did not significantly impact the incidence of esophagogastric varices. There was no significant interaction between subgroups. Meta-regression analysis showed no significant publication bias among the studies (P = 0.14).
8. Major Bleeding
Three studies reported the incidence of major bleeding in patients with acute pancreatitis-related SVT. Among SVT patients receiving anticoagulant treatment and those not receiving it, the combined incidence rates of major bleeding were 7.0% (95% CI: 1.1%–17.6%) and 3.2% (95% CI: 0.4%–8.4%), respectively. There was no significant difference in the incidence of major bleeding between the two groups (RR = 2.87, 95% CI: 1.00–8.20, P = 0.05). There was no significant heterogeneity among the studies (I² = 0%, P = 0.91).
Subgroup analysis showed that in studies of medium quality (9.5% vs. 3.1%, RR = 2.80, P = 0.05) and studies with a sample size >40 (9.5% vs. 3.1%, RR = 2.80, P = 0.05), SVT patients receiving anticoagulant treatment had a significantly higher incidence of major bleeding than those not receiving anticoagulant treatment. There was no significant interaction between subgroups.
9. Gastrointestinal Bleeding
Three studies reported the incidence of gastrointestinal bleeding in patients with acute pancreatitis-related SVT. Among SVT patients receiving anticoagulant treatment and those not receiving it, the combined incidence rates of gastrointestinal bleeding were 4.9% (95% CI: 1.4%–10.3%) and 3.9% (95% CI: 0.4%–10.6%), respectively. There was no significant difference in the incidence of gastrointestinal bleeding between the two groups (RR = 1.56, 95% CI: 0.49–5.02, P = 0.45). There was no significant heterogeneity among the studies (I² = 0%, P = 0.43).
In subgroup analyses based on study design, study quality, sample size, and anticoagulant treatment indications, anticoagulant treatment did not significantly impact the incidence of gastrointestinal bleeding. There was no significant interaction between subgroups. Meta-regression analysis showed no significant publication bias among the studies (P = 0.58).
- Summary and Outlook:
Our study concludes that anticoagulant therapy may have potential benefits for revascularization in patients with acute pancreatitis-associated splanchnic vein thrombosis (SVT), but it also carries the risk of increased bleeding. Despite these findings, further high-quality prospective studies are needed to provide a more comprehensive understanding of how anticoagulant treatment influences outcomes in patients with acute pancreatitis-associated SVT.
Call for multicenter study on the prevalence of cirrhosis PVT
Additionally, we are in the process of organizing a multicenter study to recruit participants for investigating the prevalence of portal vein thrombosis (PVT) in patients with liver cirrhosis. PVT, especially when completely obstructive, can increase portal vein pressure in cirrhotic patients, leading to an elevated risk of complications such as ascites and esophagogastric variceal bleeding. The exact prevalence of PVT in cirrhotic patients is currently unclear, and there is a lack of large-scale epidemiological studies addressing this issue in China. Therefore, we invite medical professionals from gastroenterology, hepatology, infectious diseases, radiology, and related fields to participate in this study. If you are interested, please contact Dr. Li for more detailed research information.
Contact Person: Dr. Li
Email: 1208594776@qq.com
WeChat: lqq52708
Column Initiator and Reviewer
Dr. Xingshun Qi
Deputy Chief Physician, Ph.D., Postdoctoral Fellow, Department of Gastroenterology, Northern Theater Command General Hospital.
TAG: review; Pancreatitis; Splanchnic Vein Thrombosis
