Study on the Mechanisms of Coagulation Abnormalities in Portal Vein Thrombosis in Patients with Liver Cirrhosis
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Abstract Background: This study aims to investigate the mechanisms of coagulation abnormalities in portal vein thrombosis (PVT) in patients with liver cirrhosis by collecting portal and peripheral venous blood samples through interventional methods. The differences in lipopolysaccharide (LPS), Factor VIII (FⅧ), von Willebrand factor (vWF), a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13), soluble P-selectin (sPS), and soluble CD40 ligand (sCD40L) levels between patients with liver cirrhosis and PVT and those without PVT were analyzed. Methods：A total of 40 patients diagnosed with liver cirrhosis and undergoing transjugular intrahepatic portosystemic shunt (TIPS) treatment at Hebei Provincial People's Hospital from April 2022 to October 2024 were enrolled. According to the diagnostic criteria for PVT in liver cirrhosis, patients were divided into the PVT group (n=16) and the non-PVT group (n=24). General patient information and relevant laboratory tests were collected, and differences in age, gender, etiology, medical history, body mass index (BMI), and laboratory test indicators between the two groups were compared. Portal and peripheral venous blood samples were collected through TIPS, and LPS, FⅧ, vWF, ADAMTS13, sPS, and sCD40L concentrations were measured using ELISA. The levels of these indicators in the portal and peripheral veins were compared between the PVT and non-PVT groups, and correlation analyses were performed between LPS and FⅧ, vWF, ADAMTS13, sPS, and sCD40L. Results：1.There were no significant differences between the PVT and non-PVT groups in age, gender, BMI, etiology, smoking history, alcohol consumption history, diabetes history, Model for End-Stage Liver Disease (MELD) score, white blood cell (WBC) count, neutrophil (NEUT) count, monocyte (MONO) count, lymphocytes (L), hemoglobin (Hb) level, platelet (PLT) count, albumin (ALB) level, alanine aminotransferase (ALT) level, aspartate aminotransferase (AST) level, prothrombin time (PT), prothrombin activity (PTA), international normalized ratio (INR), activated partial thromboplastin time (APTT), and thrombin time (TT) (P>0.05). However, there were significant differences between the two groups in the fibrinogen (FIB) level, and D-dimer level (P<0.05)；2.In patients with liver cirrhosis, the levels of LPS, FⅧ, vWF, sPS, and sCD40L in portal venous blood were higher than those in peripheral venous blood, while the level of ADAMTS13 was lower. These differences were statistically significant (P<0.05). Similar differences were observed in patients with liver cirrhosis and PVT. Furthermore, the levels of LPS, FⅧ, vWF, sPS, and sCD40L in portal venous blood were higher in patients with liver cirrhosis and PVT than in those without PVT, while the level of ADAMTS13 was lower. These differences were also statistically significant (P<0.05). Additionally, among the 40 patients with liver cirrhosis, FⅧ, vWF, sPS, and sCD40L were significantly correlated with LPS (P0.05). A significant correlation was observed between vWF and ADAMTS13 (P<0.05). Conclusions: Endotoxemia in patients with portal vein thrombosis in cirrhosis can activate the endothelial damage and platelet activation mechanism of the portal vein system, and then lead to local coagulation dysfunction, which plays an important role in the formation of portal vein thrombosis in cirrhosis.
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The differences in lipopolysaccharide (LPS), Factor VIII (FⅧ), von Willebrand factor (vWF), a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13), soluble P-selectin (sPS), and soluble CD40 ligand (sCD40L) levels between patients with liver cirrhosis and PVT and those without PVT were analyzed. Methods： A total of 40 patients diagnosed with liver cirrhosis and undergoing transjugular intrahepatic portosystemic shunt (TIPS) treatment at Hebei Provincial People's Hospital from April 2022 to October 2024 were enrolled. According to the diagnostic criteria for PVT in liver cirrhosis, patients were divided into the PVT group (n=16) and the non-PVT group (n=24). General patient information and relevant laboratory tests were collected, and differences in age, gender, etiology, medical history, body mass index (BMI), and laboratory test indicators between the two groups were compared. Portal and peripheral venous blood samples were collected through TIPS, and LPS, FⅧ, vWF, ADAMTS13, sPS, and sCD40L concentrations were measured using ELISA. The levels of these indicators in the portal and peripheral veins were compared between the PVT and non-PVT groups, and correlation analyses were performed between LPS and FⅧ, vWF, ADAMTS13, sPS, and sCD40L. Results： 1.There were no significant differences between the PVT and non-PVT groups in age, gender, BMI, etiology, smoking history, alcohol consumption history, diabetes history, Model for End-Stage Liver Disease (MELD) score, white blood cell (WBC) count, neutrophil (NEUT) count, monocyte (MONO) count, lymphocytes (L), hemoglobin (Hb) level, platelet (PLT) count, albumin (ALB) level, alanine aminotransferase (ALT) level, aspartate aminotransferase (AST) level, prothrombin time (PT), prothrombin activity (PTA), international normalized ratio (INR), activated partial thromboplastin time (APTT), and thrombin time (TT) (P>0.05). However, there were significant differences between the two groups in the fibrinogen (FIB) level, and D-dimer level (P<0.05)；2.In patients with liver cirrhosis, the levels of LPS, FⅧ, vWF, sPS, and sCD40L in portal venous blood were higher than those in peripheral venous blood, while the level of ADAMTS13 was lower. These differences were statistically significant (P<0.05). Similar differences were observed in patients with liver cirrhosis and PVT. Furthermore, the levels of LPS, FⅧ, vWF, sPS, and sCD40L in portal venous blood were higher in patients with liver cirrhosis and PVT than in those without PVT, while the level of ADAMTS13 was lower. These differences were also statistically significant (P<0.05). Additionally, among the 40 patients with liver cirrhosis, FⅧ, vWF, sPS, and sCD40L were significantly correlated with LPS (P0.05). A significant correlation was observed between vWF and ADAMTS13 (P<0.05). Conclusions: Endotoxemia in patients with portal vein thrombosis in cirrhosis can activate the endothelial damage and platelet activation mechanism of the portal vein system, and then lead to local coagulation dysfunction, which plays an important role in the formation of portal vein thrombosis in cirrhosis. Liver cirrhosis Portal vein thrombosis Endothelial injury Platelet activation Coagulation abnormalities LPS Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Portal vein thrombosis (PVT) is defined as the formation of thrombi within the main trunk and/or intrahepatic branches of the portal vein, with or without involvement of the mesenteric or splenic veins [ 1 ] . The incidence of PVT is only 1% in the general population [ 2 ] , whereas it affects 5–20% [ 3 ] of patients with liver cirrhosis (LC) and up to 26% [ 4 ] of individuals awaiting liver transplantation (LT) 4. As a prevalent and severe complication in cirrhotic patients, PVT exacerbates portal hypertension, increasing the risk of hemorrhage, ascites, intestinal ischemia, and mortality. Despite advances in understanding PVT pathogenesis, the mechanisms remain poorly elucidated. According to Virchow's triad, stasis of blood flow, hypercoagulability, and endothelial injury are critical determinants of venous thrombosis. Among these, a portal vein blood flow velocity < 15 cm/s is recognized as an independent predictor of PVT in cirrhosis [ 5 , 6 ] . However, the specific roles of coagulation abnormalities and endothelial injury in PVT development require further investigation. In cirrhosis, gut microbiota dysbiosis and bacterial translocation promote local inflammation and endotoxemia, contributing to a prothrombotic state in the portal venous system [ 7 ] . Notably, lipopolysaccharide (LPS), a key component of Gram-negative bacterial cell walls, acts as a pivotal mediator of bacterial translocation. By activating Toll-like receptor 4 (TLR4)-dependent pathways, LPS induces endothelial release of procoagulant factors (e.g., human coagulation factor VIII FVIII and von Willebrand factor vWF) and activates platelets, enhancing their expression of soluble P-selectin (sPS) and soluble CD40 ligand (sCD40L) [ 8 – 10 ] . These processes have been implicated in thrombogenesis across diverse diseases, including deep vein thrombosis, coronary artery disease, and diabetes 8–10. However, whether LPS-driven endothelial injury and platelet activation contribute to PVT in cirrhosis remains inconclusive. To address this gap, we employed transjugular intrahepatic portosystemic shunt (TIPS) to obtain paired portal and peripheral venous blood samples from cirrhotic patients with and without PVT. Using enzyme-linked immunosorbent assays (ELISAs), we quantified LPS, endothelial injury markers (vWF, FVIII), and platelet activation markers (sPS, sCD40L). Correlation analyses were conducted to explore the interplay between LPS and these biomarkers, aiming to elucidate the pathogenic mechanisms of endothelial dysfunction and platelet activation in PVT development. This study provides novel insights into the molecular basis of PVT in cirrhosis and identifies potential therapeutic targets. Materials and Methods 1.1 Study Population This case-control study enrolled 40 patients with liver cirrhosis who underwent transjugular intrahepatic portosystemic shunt (TIPS) at Hebei Provincial People’s Hospital between April 2022 and October 2024. 1.2 Inclusion and Exclusion Criteria Inclusion Criteria:Patients were diagnosed with cirrhosis based on imaging (1) Doppler ultrasound, (2) contrast-enhanced CT, or MRPortal vein thrombosis is clearly present. For patients with suspected PVT but insufficient diagnostic evidence of cirrhosis, additional confirmation was obtained via hepatic venous pressure gradient measurement and percutaneous transhepatic liver biopsy. Exclusion Criteria:(1) Primary or secondary malignant liver tumors;(2) Concurrent other malignancies;(3) Hematologic disorders;(4) Budd-Chiari syndrome or non-cirrhotic PVT;(5) Severe infections;(6) Anticoagulant therapy for other thrombotic diseases. Patients were stratified into PVT (n=20) and non-PVT groups (n=20). The study was approved by the Ethics Committee of Hebei Provincial People’s Hospital. 1.3 Research Methods Clinical data were collected, including age, sex, body mass index (BMI), etiology, smoking/alcohol history, past medical history, laboratory parameters (complete blood count, comprehensive biochemistry, and coagulation profile), and the Model for End-Stage Liver Disease (MELD) score. During TIPS procedures: Portal venous blood was sampled immediately after successful portal vein puncture, along with right internal jugular venous blood. Blood samples (5 mL) were collected in tubes containing 3.8% sodium citrate anticoagulant, centrifuged at 3000 rpm for 15 minutes at 4°C, and stored at −80°C.Enzyme-linked immunosorbent assays (ELISAs) were used to quantify plasma levels of lipopolysaccharide (LPS), factor VIII (FVIII), von Willebrand factor (vWF), soluble P-selectin (sPS), soluble CD40 ligand (sCD40L), and ADAMTS13 (Jiangsu Jingmei Biotechnology Co., Ltd.). Results 2.1 Comparison of Baseline Characteristics Between Groups PVT patients exhibited significantly higher fibrinogen (FIB) and D-dimer levels compared to non-PVT patients (P < 0.05), indicating poorer liver function and a hypercoagulable state in the PVT group (Table 1). Table 1. Comparison of Baseline Characteristics Between PVT and Non-PVT Groups PVT group (n = 16) Non-PVT group (n = 24) statistic P Age (years) 56.31 ± 10.02 57.46 ± 13.21 t =-0.29 0.770 Gender [n(%)] χ² =0.07 0.792 woman 6 (37.50) 10 (41.67) man 10 (62.50) 14 (58.33) BMI(kg/m 2 ) 24.36 ± 3.44 25.93 ± 4.40 χ² =1.20 1.238 Drinking history [ n (%)] χ² =0.16 0.685 Smoking history [n (%)] χ² =0.04 0.833 cause of disease [n (%)] - 0.681 viral 5(31.25) 10(41.67) alcoholic 2(12.50) 4(16.67) autoimmunity 0(0.00) 2(8.33) Primary biliary 1(6.25) 1(4.17) other 8(50.00) 7(29.17) MELD评分 8.59 (6.48, 9.93) 9.75 (7.69, 11.11) Z =-1.42 0.155 WBC(10 9 /L) 5.02 (3.25, 7.36) 3.94 (2.67, 5.21) Z =-1.14 0.255 NEUT(10 9 /L) 3.46 (2.45, 5.82) 2.73 (1.54, 3.45) Z =-1.52 0.129 MONO(109/L) 0.29 (0.19, 0.57) 0.22 (0.15, 0.45) Z =-1.16 0.246 LYM(109/L) 0.61 (0.51, 0.83) 0.74 (0.51, 0.99) Z =-0.64 0.525 Hb(g/L) 97.12 ± 31.48 85.33 ± 20.85 t =-1.32 0.200 PLT(109/L) 101.00 (48.25, 233.50) 75.50 (37.75, 100.00) Z =-1.79 0.073 ALB(g/L) 33.59 ± 4.24 34.90 ± 6.54 t =-0.70 0.485 AST(U/L) 37.35 (23.00, 55.42) 28.75 (21.45, 37.53) Z =-0.97 0.334 ALT(U/L) 26.80 (15.07, 49.88) 19.35 (11.15, 31.90) Z =-1.28 0.199 PT(s) 13.05 (12.50, 14.33) 13.35 (12.80, 15.42) Z =-0.98 0.327 PTA(%) 78.81 ± 14.61 72.80 ± 17.74 t =--1.12 0.268 INR 1.15 (1.06, 1.23) 1.17 (1.10, 1.35) Z =-1.31 0.189 APTT(s) 29.25 (26.62, 31.83) 26.95 (25.12, 27.90) Z =-1.52 0.129 FIB(g/L) 2.46 (1.73, 3.48)* 2.00 (1.25, 2.40) Z =-2.17 0.030 TT(s) 17.95 (17.20, 19.15) 18.35 (17.28, 19.80) Z =-0.36 0.720 D-dimer (mg/L) 5.85 (3.10, 8.96)* 1.50 (0.59, 3.45) Z =-3.36 < 0.001 Note:BMI: Body Mass Index;MELD: Model for End-Stage Liver Disease;WBC: White Blood Cell Count;NEUT: Neutrophil Count;MONO: Monocyte Count;LYM: Lymphocyte Count;Hb: Hemoglobin;PLT: Platelet Count;ALB: Albumin;AST: Aspartate Aminotransferase;ALT: Alanine Aminotransferase;PT: Prothrombin Time;PTA: Prothrombin Time Activity;INR: International Normalized Ratio;APTT: Activated Partial Thromboplastin Time;FIB: Fibrinogen;TT: Thrombin Time;P < 0.05 indicates statistical significance. 2.2 Comparison of Endothelial Injury and Platelet Activation Markers 2.1 Comparison Between Portal and Peripheral Venous Levels in All Patients In 40 cirrhotic patients, portal venous concentrations of LPS, FVIII, vWF, sPS, and sCD40L were significantly higher than peripheral venous levels, while ADAMTS13 was markedly lower (P < 0.05). These findings indicate a concentration gradient disparity between portal and peripheral compartments, reflecting localized endothelial injury and platelet activation in the portal circulation (Table 2; Fig. 1). Table 2. Comparison of Endothelial/Platelet Markers in Portal vs. Peripheral Venous Blood Portal vein (n = 40) Peripheral venous (n = 40) statistic P LPS(pg/mL) 85.37 ± 25.72* 77.50 ± 24.13 t < 0.001 < 0.001 FⅧ(pg/mL) 86.54 (75.26, 93.55) * 78.03 (64.94, 88.19) Z = 76.000 < 0.001 vWF(pg/mL) 51.61 (44.37, 65.47) * 49.29 (40.25, 61.83) Z = 116.000 < 0.001 ADAMTS-13(pg/mL) 70.15 (56.41, 83.75) * 77.47 (66.12, 87.02) Z = 671.000 < 0.001 sPS(pg/mL) 3.83 (3.57, 4.66) * 3.61 (3.08, 4.40) Z = 42.000 < 0.001 sCD40L(pg/mL) 3.01 (2.62, 4.05) * 2.69 (2.37, 3.74) Z = 17.000 < 0.001 *Significant difference (P < 0.05). 2.2.2 Comparison of portal vein and peripheral vein endothelial injury and platelet activation markers in patients with liver cirrhosis PVT In 16 cirrhotic patients with PVT, portal venous concentrations of LPS, FVIII, vWF, sPS, andsCD40L were significantly higher than peripheral venous levels, whileADAMTS13 was markedly lower (P < 0.05). These findings confirm a concentration gradient disparity between portal and peripheral compartments in PVT patients, suggesting localized endothelial dysfunction and platelet activation (Table 3; Fig. 2 ). Table 3. Comparison of Endothelial and Platelet Markers in Portal and Peripheral Venous Blood in PVT Patients Portal vein (n = 16) Peripheral venous (n = 16) statistic P LPS(pg/mL) 106.29 ± 17.45* 96.71 ± 15.44 t < 0.001 < 0.001 FⅧ(pg/mL) 93.67 (89.15, 107.56) * 87.27 (75.55, 99.72) Z = 3.000 < 0.001 vWF(pg/mL) 71.72 ± 24.01* 62.39 ± 19.32 t < 0.001 < 0.001 ADAMTS-13(pg/mL) 57.99 ± 22.20* 62.90 ± 23.53 t = 2.781 0.014 sPS(pg/mL) 6.04 (3.73, 11.60) * 5.65 (3.60, 10.07) Z < 0.001 < 0.001 sCD40L(pg/mL) 7.77 (2.85, 11.45) * 7.29 (2.63, 11.06) Z < 0.001 < 0.001 *Significant difference (P < 0.05). 2.2.3 Comparison of Endothelial Injury and Platelet Activation Markers Between PVT and Non-PVT Patients In cirrhotic patients with PVT, portal venous concentrations of LPS, FVIII, vWF, sPS, and sCD40L were significantly higher compared to non-PVT patients, while ADAMTS13 levels were markedly lower (P < 0.05). These findings demonstrate distinct gradients of endothelial injury and platelet activation markers in the portal circulation of PVT patients (Table 4; Fig. 3 ). Table 4. Comparison of Endothelial and Platelet Markers in Portal Venous Blood Between PVT and Non-PVT Groups PVT group (n = 16) Non-PVT group (n = 24) statistic P LPS(pg/mL) 102.60 (97.03, 112.56) * 75.59 (60.09, 83.38) Z =-4.68 < 0.001 FⅧ(pg/mL) 93.67 (89.15, 107.56) * 78.02 (61.04, 88.33) Z =-3.62 < 0.001 vWF(pg/mL) 70.15 (52.50, 79.16) * 45.98 (42.80, 53.04) Z =-3.52 < 0.001 ADAMTS-13(pg/mL) 57.16 (51.38, 76.71) * 74.43 (65.62, 87.67) Z =-2.33 0.020 sPS(pg/mL) 6.04 (3.73, 11.60) * 3.76 (3.27, 3.94) Z =-3.17 0.002 sCD40L(pg/mL) 7.77 (2.85, 11.45) * 2.71 (2.50, 3.28) Z =-3.33 < 0.001 *Significant difference (P < 0.05). 2.3 Correlation Analysis Between Portal LPS Levels and Endothelial/Platelet Markers in 40 Cirrhotic Patients In 40 cirrhotic patients, portal LPS concentration showed significant positive correlations with FVIII (R² = 0.47, P < 0.0001), vWF (R² = 0.37, P 0.05). Additionally, vWF levels exhibited a negative correlation with ADAMTS13 (R² = 0.15, P = 0.0139) (Fig. 4 ). Discussion This study demonstrated that cirrhotic patients with portal vein thrombosis (PVT) exhibit a significant gradient of endothelial injury and platelet activation markers in the portal venous system compared to peripheral circulation, with markedly elevated levels in the portal vein. Further analysis revealed that this phenomenon was closely associated with lipopolysaccharide (LPS). Cirrhosis, characterized by severe hepatic architectural distortion and nodular regeneration, compresses hepatic sinusoids and vasculature, increasing intrahepatic resistance and culminating in portal hypertension. Portal hypertension profoundly impacts intestinal permeability, gut microbiota balance, and bacterial translocation. By reducing mucosal blood flow and promoting neovascularization, cirrhotic portal hypertension induces intestinal ischemia and edema, disrupting the intestinal barrier and facilitating bacterial-derived LPS translocation into the portal circulation [ 12 , 13 ] . Once in the circulatory system, LPS interacts with Toll-like receptors (Toll-like receptors, TLRs) and triggers a series of pathophysiological changes associated with the formation of PVT. On one hand, LPS binds to TLRs expressed on hepatocytes and immune cells. The activation of these cells triggers the release of large amounts of inflammatory mediators, chemokines, vasoactive substances, adhesion molecules, and reactive oxygen species (Reactive Oxygen Species, ROS) [14], leading to systemic inflammatory responses, promoting hepatostellate cell proliferation, and the progression of liver cirrhosis[15]. On the other hand, LPS binds to TLRs expressed on vascular endothelial cells, platelets, and neutrophils, promoting a hypercoagulable state and PVT[16]in the context of liver cirrhosis. Von Willebrand factor (vWF), a marker of endothelial dysfunction [ 17 ] , and factor VIII (FVIII), a key indicator of hypercoagulability in cirrhosis [ 18 , 19 ] , play critical roles in hemostasis and thrombogenesis. This study demonstrated that FVIII levels in the portal vein are significantly elevated in cirrhotic patients compared to peripheral venous levels, consistent with Delahousse et al.’s findings [ 20 ] . These results indicate a sustained prothrombotic state within the portal circulation of cirrhotic patients [ 21 ] , where enhanced FVIII activity represents a major mechanism driving portal hypercoagulability.Carnevale et al. [ 11 ] demonstrated that serum levels of LPS, FVIII, and vWF are significantly elevated in cirrhotic patients compared to non-cirrhotic controls, with strong positive correlations between LPS and both FVIII and vWF. In vitro studies further revealed that LPS stimulates Weibel-Palade body (WPB) formation and secretion via TLR4 signaling, prompting human umbilical vein endothelial cells (HUVECs) to release FVIII and vWF. Consistent with these findings, our study revealed markedly higher portal venous levels of LPS, FVIII, and vWF in cirrhotic PVT patients compared to peripheral circulation, establishing a concentration gradient disparity. Moreover, the significant correlations between LPS, FVIII, and vWF in portal blood align with prior evidence [ 22 ] , underscoring the role of LPS as a potential trigger for endothelial injury and hypercoagulability in cirrhotic PVT.ADAM (A Disintegrin and Metalloproteinase) and its subfamily ADAMTS (ADAM with thrombospondin motifs) are proteases predominantly synthesized by hepatic stellate cells and play critical regulatory roles in hemostasis. ADAMTS-13, a key member of this subfamily, acts as the von Willebrand factor-cleaving protease (vWFCP), cleaving ultra-large von Willebrand factor multimers (UL-vWFM) into smaller, less thrombogenic fragments [ 23 ] . In cirrhosis, reduced ADAMTS-13 activity or levels lead to accumulation of UL-vWFM, which stabilize platelet aggregates and promote thrombus formation. This dysregulation is compounded by vWF’s role as an FVIII carrier; activated UL-vWFM enhances FVIII stability and activity, amplifying the intrinsic coagulation pathway .Lancellotti et al. [ 24 ] demonstrated that ADAMTS-13 activity is significantly lower in cirrhotic PVT patients compared to non-PVT controls, and this deficiency correlates independently with PVT risk [ 24 ] . Tomasz and colleagues further validated that low serum ADAMTS-13 levels serve as a robust predictor of PVT in decompensated cirrhosis, independent of Child-Pugh or MELD scores [ 25 ] . Our study extends these findings by revealing markedly reduced ADAMTS-13 levels in the portal venous system of cirrhotic PVT patients. Notably, portal vWF levels exhibited a significant inverse correlation with ADAMTS-13, while vWF positively correlated with LPS, underscoring ADAMTS-13’s pivotal role in PVT pathogenesis. ADAMTS-13 primarily exerts its influence by modulating vWF levels, further highlighting its potential role in the pathological mechanisms of PVT in liver cirrhosis. As the condition of patients with liver cirrhosis deteriorates, the enzymatic activity of ADAMTS-13 produced by hepatic stellate cells gradually diminishes, leading to a sustained decline in ADAMTS-13 levels [ 24 ] . Inflammatory cytokines released under the pathophysiological state of liver cirrhosis may affect the balance between the number of ULVWF polymers released by endothelial cells and the rate at which ADAMTS-13 cleaves ULVWF. Therefore, in the context of endotoxemia and inflammation associated with decompensated liver cirrhosis, the decrease in ADAMTS-13 levels is likely to contribute to portal vein thrombosis in patients with liver cirrhosis Patients with liver cirrhosis are more prone to thrombocytopenia due to various factors such as reduced platelet production, abnormal distribution, and increased destruction, thereby increasing the risk of bleeding. However, some studies have indicated that [ 26 – 28 ] , the platelets in patients with liver cirrhosis are in an activated state, which is not influenced by the number of platelets and is closely associated with endotoxemia. Endotoxemia leads to elevated levels of LPS in circulation, which can activate Toll-like receptor 4 (TLR4) on the surface of platelets, enhancing their responsiveness to agonists (such as collagen and ADP), promoting platelet aggregation and thrombus formation [ 29 ] . Additionally, LPS can activate Toll-like receptor 2 (TLR2) on the surface of platelets, increasing the release of α granules and dense granules, facilitating interaction between platelets and vascular endothelial cells, further promoting platelet-dependent thrombus formation [ 30 , 31 ] Valeria et al. [ 29 ] demonstrated that levels of LPS, soluble CD40 ligand (sCD40L), and soluble P-selectin (sPS) are significantly elevated in the systemic circulation of cirrhotic patients, providing the first direct evidence linking LPS to platelet activation and thrombotic complications in cirrhosis. Their in vitro studies further revealed that LPS activates platelets via Toll-like receptor 4 (TLR4), enhancing platelet reactivity to agonists such as collagen and ADP. This finding aligns with our observation of elevated sCD40L and sPS in the portal venous system of cirrhotic PVT patients, underscoring their role as biomarkers of thrombotic risk. The role of LPS-mediated oxidative stress in platelet activation has emerged as a critical driver of portal vein thrombosis (PVT) in cirrhosis [ 29 ] . Our previous studies demonstrated that soluble NOXA2 derivative (sNOX2-dp), a marker of NADPH oxidase (NOX2) activation, is significantly elevated in the portal venous system of cirrhotic PVT patients compared to non-PVT controls, with a strong positive correlation to LPS levels. These findings align with Stefania et al.’s work [ 26 ] , which showed systemic increases in sNOX2-dp, sPS, and sCD40L in cirrhotic patients, further highlighting the interdependence of oxidative stress and platelet activation. This study further reveals that sCD40L and sPS levels in the portal venous system of cirrhotic PVT patients are significantly elevated compared to peripheral venous levels, with strong positive correlations to LPS concentrations. These findings underscore the enhanced platelet activation in the portal circulation, particularly in PVT patients, and highlight the central role of LPS-mediated oxidative stress in driving this pathology. This study provides further evidence supporting the heightened significance of endothelial injury and platelet activation in the portal venous circulation of cirrhotic patients with portal vein thrombosis (PVT), both of which are closely associated with lipopolysaccharide (LPS). These findings suggest that modulating LPS levels may represent a therapeutic strategy to reduce PVT risk in cirrhotic patients. Dynamic monitoring of endothelial injury and platelet activation markers, coupled with timely intervention to suppress platelet hyperactivity, could serve as critical therapeutic targets for managing PVT in cirrhosis. Abbreviations TIPS Transjugular intrahepatic portosystemic shunt PVT Portal Vein Thrombosis PAMPs Pathogen-Associa ted Molecular Patterns LPS Lipopolysaccharide TLR4 Toll like receptor 4 FⅧ Human Coagulation Factor Ⅷ vWF von Willebrand Factor sPS soluble P-selectin sCD40L soluble CD40 Ligand TLRs Toll-like receptors ROS Reactive Oxygen Species WPB Weibel-Palade body HUVEC Human Umbilical Vein Endothelial Cells vWFCP von Willebrand factor-cleaving protease UL-VWFM Ultra-Large von Willebrand Factor Multimers IL-8 Interleukin-8 IL-6 Interleukin-6 TNF-α Tumor Necrosis Factor-α sNOX2-dp soluble NOXA2 derivative sGPVI soluble glycoprotein VI Declarations Acknowledgements Not applicable. Author contributions XuXu Yang was responsible for conception , design of study , drafting of manuscript and critical revision. Ping Qi was responsible for the data analysis and/or interpretation. Wei Sang, Pingping Li, Yueqin Li and Yun Bai were responsible for approvaling of final version of manuscript. The authors read and approved the final manuscript. Funding This work was supported by in 2022, the government will support the Training project of clinical medical talents, subject number: 20220017. Data availability The original data generated in the course of the study are from Hebei Provincial People's Hospital. (We are in the process of uploading the raw data to the database, but it will take some time for the upload to be successful) Ethics approval and consent to participate The study was approved by the Ethics Committee of Hebei Provincial People's Hospital, and every participant signed informed consent. The written informed consent of all subjects was obtained following the Declaration of Helsinki. Consent for publication Not applicable. Competing interests The authors declare no competing interests. References Qi Xingshun Y, Ling. Expert consensus on management of portal vein thrombosis in liver cirrhosis (2020, Shanghai) [J]. J Clin Hepatobiliary Dis. 2020;36(12):2667–74. Ogren M, Bergqvist D, Björck M, et al. Portal vein thrombosis: prevalence, patient characteristics and lifetime risk: a population study based on 23,796 consecutive autopsies [J]. World J Gastroenterol. 2006;12(13):2115–9. Chen H, Trilok G, Wang F, et al. A single hospital study on portal vein thrombosis in cirrhotic patients - clinical characteristics & risk factors [J]. Indian J Med Res. 2014;139(2):260–6. Ponziani FR, Zocco MA, Senzolo M, et al. Portal vein thrombosis and liver transplantation: implications for waiting list period, surgical approach, early and late follow-up [J]. Transpl Rev (Orlando). 2014;28(2):92–101. Zocco MA, Di Stasio E, De Cristofaro R, et al. Thrombotic risk factors in patients with liver cirrhosis: correlation with MELD scoring system and portal vein thrombosis development [J]. J Hepatol. 2009;51(4):682–9. Stine JG, Wang J, Shah PM, et al. Decreased portal vein velocity is predictive of the development of portal vein thrombosis: A matched case-control study [J]. Liver Int. 2018;38(1):94–101. Branchford BR, Carpenter SL. The Role of Inflammation in Venous Thromboembolism [J]. Front Pediatr. 2018;6:142. Carnevale R, Sciarretta S, Valenti V, et al. Low-grade endotoxaemia enhances artery thrombus growth via Toll-like receptor 4: implication for myocardial infarction [J]. Eur Heart J. 2020;41(33):3156–65. Poredos P, Jezovnik MK. Endothelial Dysfunction and Venous Thrombosis [J]. Angiology. 2018;69(7):564–7. Nie G, Zhang H, Xie D, et al. Liver cirrhosis and complications from the perspective of dysbiosis [J]. Front Med (Lausanne). 2023;10:1320015. Carnevale R, Raparelli V, Nocella C, et al. Gut-derived endotoxin stimulates factor VIII secretion from endothelial cells. Implications for hypercoagulability in cirrhosis [J]. J Hepatol. 2017;67(5):950–6. Artoni A, Abbattista M, Bucciarelli P, et al. Platelet to Lymphocyte Ratio and Neutrophil to Lymphocyte Ratio as Risk Factors for Venous Thrombosis [J]. Clin Appl Thromb Hemost. 2018;24(5):808–14. Arab JP, Martin-Mateos RM, Shah VH. Gut-liver axis, cirrhosis and portal hypertension: the chicken and the egg [J]. Hepatol Int. 2018;12(Suppl 1):24–33. Custodio-Chablé SJ, Lezama RA, Reyes-Maldonado E. Platelet activation as a trigger factor for inflammation and atherosclerosis [J]. Cir Cir. 2020;88(2):233–43. Tsuchida T, Friedman SL. Mechanisms of hepatic stellate cell activation [J]. Nat Rev Gastroenterol Hepatol. 2017;14(7):397–411. Hasan RA, Koh AY, Zia A. The gut microbiome and thromboembolism [J]. Thromb Res. 2020;189:77–87. Horvath B, Hegedus D, Szapary L, et al. Measurement of von Willebrand factor as the marker of endothelial dysfunction in vascular diseases [J]. Exp Clin Cardiol. 2004;9(1):31–4. Wang, Qi. Zhao Yiming. Advances in the study of the relationship between hemophilia factors and liver diseases [J]. Chin J Hepatol. 2018;26(11):877–80. Sinegre T, Duron C, Lecompte T, et al. Increased factor VIII plays a significant role in plasma hypercoagulability phenotype of patients with cirrhosis [J]. J Thromb Haemost. 2018;16(6):1132–40. Delahousse B, Labat-Debelleix V, Decalonne L, et al. Comparative study of coagulation and thrombin generation in the portal and jugular plasma of patients with cirrhosis [J]. Thromb Haemost. 2010;104(4):741–9. Violi F, Ferro D, Basili S, et al. Ongoing prothrombotic state in the portal circulation of cirrhotic patients [J]. Thromb Haemost. 1997;77(1):44–7. Praktiknjo M, Trebicka J, Carnevale R, et al. Von Willebrand and Factor VIII Portosystemic Circulation Gradient in Cirrhosis: Implications for Portal Vein Thrombosis [J]. Clin Transl Gastroenterol. 2020;11(2):e00123. Bernardo A, Ball C, Nolasco L, et al. Effects of inflammatory cytokines on the release and cleavage of the endothelial cell-derived ultralarge von Willebrand factor multimers under flow [J]. Blood. 2004;104(1):100–6. Lancellotti S, Basso M, Veca V, et al. Presence of portal vein thrombosis in liver cirrhosis is strongly associated with low levels of ADAMTS-13: a pilot study [J]. Intern Emerg Med. 2016;11(7):959–67. Mikuła T, Kozłowska J, Stańczak W et al. Serum ADAMTS-13 Levels as an Indicator of Portal Vein Thrombosis [J]. Gastroenterol Res Pract, 2018, 2018: 3287491. Basili S, Raparelli V, Riggio O, et al. NADPH oxidase-mediated platelet isoprostane over-production in cirrhotic patients: implication for platelet activation [J]. Liver Int. 2011;31(10):1533–40. Chen, Zhiji. He Song. Advances in the Study of Pathogenesis of Portal Venous Thrombosis in Liver Cirrhosis [J]. J Gastroenterol Hepatol. 2021. 10.3969/j.issn.1006-5709.2021.04.020 . Queck A, Carnevale R, Uschner FE, et al. Role of portal venous platelet activation in patients with decompensated cirrhosis and TIPS [J]. Gut. 2020;69(8):1535–6. Raparelli V, Basili S, Carnevale R, et al. Low-grade endotoxemia and platelet activation in cirrhosis [J]. Hepatology. 2017;65(2):571–81. Blair P, Rex S, Vitseva O, et al. Stimulation of Toll-like receptor 2 in human platelets induces a thromboinflammatory response through activation of phosphoinositide 3-kinase [J]. Circ Res. 2009;104(3):346–54. Rex S, Beaulieu LM, Perlman DH, et al. Immune versus thrombotic stimulation of platelets differentially regulates signalling pathways, intracellular protein-protein interactions, and alpha-granule release [J]. Thromb Haemost. 2009;102(1):97–110. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 07 Aug, 2025 Reviewers invited by journal 15 Jul, 2025 Editor assigned by journal 09 Jul, 2025 Editor invited by journal 19 Jun, 2025 Submission checks completed at journal 18 Jun, 2025 First submitted to journal 18 Jun, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6794559","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":485927890,"identity":"b7772176-a523-4df3-964c-6b393dc578cc","order_by":0,"name":"Xuxu YANG","email":"","orcid":"","institution":"Hebei North University","correspondingAuthor":false,"prefix":"","firstName":"Xuxu","middleName":"","lastName":"YANG","suffix":""},{"id":485927891,"identity":"fbc6244f-1323-4c10-857f-f7d21aa27feb","order_by":1,"name":"Ping QI","email":"","orcid":"","institution":"Hebei North University","correspondingAuthor":false,"prefix":"","firstName":"Ping","middleName":"","lastName":"QI","suffix":""},{"id":485927892,"identity":"5b0066aa-a5dc-4c31-b605-0e1ce21b0e8b","order_by":2,"name":"Wei SANG","email":"","orcid":"","institution":"Hebei General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Wei","middleName":"","lastName":"SANG","suffix":""},{"id":485927893,"identity":"b0a8abda-9664-498c-b699-bd99192e9383","order_by":3,"name":"Pingping LI","email":"","orcid":"","institution":"Hebei General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Pingping","middleName":"","lastName":"LI","suffix":""},{"id":485927894,"identity":"e6d1c645-3ea6-4dc8-8687-347976d0b54f","order_by":4,"name":"Yueqin LI","email":"","orcid":"","institution":"Hebei General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yueqin","middleName":"","lastName":"LI","suffix":""},{"id":485927895,"identity":"dbab5e62-5e5d-4ed0-9938-586b1c33b063","order_by":5,"name":"Yun BAI","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAx0lEQVRIiWNgGAWjYBACPgYGZiBlAcTJBw58qCBCCxtEiwQQpyUenHGGNC05xod5W4jRIpH82JinRkLO4HjOhwO8DQzy/GIHCGlJM07mOSZhbHDm7YYDkjsYDGfOTiCkJYf5MG+DROKGG7kbDhieYUgwuE28lpwHBxLbiNSSDNXCcOAgUVp4nhkbzgH6RfLMM4ODDWckCPuFnz35scSbGhs5vuPJjz//qbCR55cmoAUEmHgQbAnCykGA8Qdx6kbBKBgFo2CkAgBZkENawjLIQQAAAABJRU5ErkJggg==","orcid":"","institution":"Hebei General Hospital","correspondingAuthor":true,"prefix":"","firstName":"Yun","middleName":"","lastName":"BAI","suffix":""}],"badges":[],"createdAt":"2025-06-01 08:23:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6794559/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6794559/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":87318111,"identity":"9ff2aab4-9680-4030-b61b-62643d7004dc","added_by":"auto","created_at":"2025-07-22 16:15:02","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":17421,"visible":true,"origin":"","legend":"\u003cp\u003eComparison Concentration Gradients of Endothelial and Platelet Markers Between Portal and Peripheral Venous Blood. Levels of LPS(A), FVIII(B), vWF(C), ADAMTS-13(D), sPS(E) and sCD40L(F) in the portal and peripheral venous blood of patients with cirrhosis.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6794559/v1/4e7efba790fb9fdccca8b322.png"},{"id":87318112,"identity":"7cc5c14d-1d20-46d3-bf61-6dcbaf231f29","added_by":"auto","created_at":"2025-07-22 16:15:03","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":15971,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of Endothelial and Platelet Markers in Portal and Peripheral Venous Blood in PVT Patients. Levels of LPS(A), FVIII(B), vWF(C), ADAMTS-13(D), sPS(E) and sCD40L(F) in the portal and peripheral venous blood of patients with PVT cirrhosis.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6794559/v1/b9cd2978da19593dec85b018.png"},{"id":87318110,"identity":"fd51e5f7-cd09-4263-8ac6-7375c6cdb385","added_by":"auto","created_at":"2025-07-22 16:15:02","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":21652,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of Endothelial and Platelet Markers in Portal Venous Blood Between PVT and Non-PVT Groups. Levels of LPS(A), FVIII(B), vWF(C), ADAMTS-13(D), sPS(E) and sCD40L(F) in the PVT and Non-PVT Patients.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-6794559/v1/3078fb0e2d306ec1d650d0f4.png"},{"id":87318114,"identity":"1496d8f4-8be6-484d-80e0-8fb9a517864a","added_by":"auto","created_at":"2025-07-22 16:15:03","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":20804,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelation Analysis Between Portal LPS Levels and Endothelial/Platelet Markers in Cirrhotic Patients.\u003c/p\u003e\n\u003cp\u003ePanel A reports Spearman Correlation Coefficient between FVIII and LPS;\u003c/p\u003e\n\u003cp\u003ePanel B reports Spearman Correlation Coefficient between vWF and LPS;\u003c/p\u003e\n\u003cp\u003ePanel C reports Spearman Correlation Coefficient between sPS and LPS;\u003c/p\u003e\n\u003cp\u003ePanel D reports Spearman Correlation Coefficient between sCD40L and LPS;\u003c/p\u003e\n\u003cp\u003ePanel E reports Spearman Correlation Coefficient between ADAMTS13 and LPS;\u003c/p\u003e\n\u003cp\u003ePanel F reports Spearman Correlation Coefficient between vWF and ADAMTS13.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-6794559/v1/cf0bfcda8bd2292412f42a65.png"},{"id":87322352,"identity":"ec655d52-141b-408b-8cba-afa3f14aa1c4","added_by":"auto","created_at":"2025-07-22 16:47:03","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":733675,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6794559/v1/540dc2b7-233f-40f2-bd7b-c9cb0438fef4.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Study on the Mechanisms of Coagulation Abnormalities in Portal Vein Thrombosis in Patients with Liver Cirrhosis","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePortal vein thrombosis (PVT) is defined as the formation of thrombi within the main trunk and/or intrahepatic branches of the portal vein, with or without involvement of the mesenteric or splenic veins\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. The incidence of PVT is only 1% in the general population\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e, whereas it affects 5\u0026ndash;20%\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e of patients with liver cirrhosis (LC) and up to 26%\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e of individuals awaiting liver transplantation (LT) 4. As a prevalent and severe complication in cirrhotic patients, PVT exacerbates portal hypertension, increasing the risk of hemorrhage, ascites, intestinal ischemia, and mortality.\u003c/p\u003e\u003cp\u003eDespite advances in understanding PVT pathogenesis, the mechanisms remain poorly elucidated. According to Virchow's triad, stasis of blood flow, hypercoagulability, and endothelial injury are critical determinants of venous thrombosis. Among these, a portal vein blood flow velocity\u0026thinsp;\u0026lt;\u0026thinsp;15 cm/s is recognized as an independent predictor of PVT in cirrhosis\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. However, the specific roles of coagulation abnormalities and endothelial injury in PVT development require further investigation. In cirrhosis, gut microbiota dysbiosis and bacterial translocation promote local inflammation and endotoxemia, contributing to a prothrombotic state in the portal venous system\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. Notably, lipopolysaccharide (LPS), a key component of Gram-negative bacterial cell walls, acts as a pivotal mediator of bacterial translocation. By activating Toll-like receptor 4 (TLR4)-dependent pathways, LPS induces endothelial release of procoagulant factors (e.g., human coagulation factor VIII FVIII and von Willebrand factor vWF) and activates platelets, enhancing their expression of soluble P-selectin (sPS) and soluble CD40 ligand (sCD40L)\u003csup\u003e[\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. These processes have been implicated in thrombogenesis across diverse diseases, including deep vein thrombosis, coronary artery disease, and diabetes 8\u0026ndash;10. However, whether LPS-driven endothelial injury and platelet activation contribute to PVT in cirrhosis remains inconclusive.\u003c/p\u003e\u003cp\u003eTo address this gap, we employed transjugular intrahepatic portosystemic shunt (TIPS) to obtain paired portal and peripheral venous blood samples from cirrhotic patients with and without PVT. Using enzyme-linked immunosorbent assays (ELISAs), we quantified LPS, endothelial injury markers (vWF, FVIII), and platelet activation markers (sPS, sCD40L). Correlation analyses were conducted to explore the interplay between LPS and these biomarkers, aiming to elucidate the pathogenic mechanisms of endothelial dysfunction and platelet activation in PVT development. This study provides novel insights into the molecular basis of PVT in cirrhosis and identifies potential therapeutic targets.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e1.1 Study Population\u003c/p\u003e\n\u003cp\u003eThis case-control study enrolled 40 patients with liver cirrhosis who underwent transjugular intrahepatic portosystemic shunt (TIPS) at Hebei Provincial People\u0026rsquo;s Hospital between April 2022 and October 2024.\u003c/p\u003e\n\u003cp\u003e1.2 Inclusion and Exclusion Criteria\u003c/p\u003e\n\u003cp\u003eInclusion Criteria:Patients were diagnosed with cirrhosis based on imaging (1) Doppler ultrasound, (2) contrast-enhanced CT, or MRPortal vein thrombosis is clearly present. For patients with suspected PVT but insufficient diagnostic evidence of cirrhosis, additional confirmation was obtained via hepatic venous pressure gradient measurement and percutaneous transhepatic liver biopsy.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eExclusion Criteria:(1) Primary or secondary malignant liver tumors;(2) Concurrent other malignancies;(3) Hematologic disorders;(4) Budd-Chiari syndrome or non-cirrhotic PVT;(5) Severe infections;(6) Anticoagulant therapy for other thrombotic diseases. Patients were stratified into PVT (n=20) and non-PVT groups (n=20). The study was approved by the Ethics Committee of Hebei Provincial People\u0026rsquo;s Hospital.\u003c/p\u003e\n\u003cp\u003e1.3 Research Methods\u003c/p\u003e\n\u003cp\u003eClinical data were collected, including age, sex, body mass index (BMI), etiology, smoking/alcohol history, past medical history, laboratory parameters (complete blood count, comprehensive biochemistry, and coagulation profile), and the Model for End-Stage Liver Disease (MELD) score. During TIPS procedures:\u003c/p\u003e\n\u003cp\u003ePortal venous blood was sampled immediately after successful portal vein puncture, along with right internal jugular venous blood.\u003c/p\u003e\n\u003cp\u003eBlood samples (5 mL) were collected in tubes containing 3.8% sodium citrate anticoagulant, centrifuged at 3000 rpm for 15 minutes at 4\u0026deg;C, and stored at \u0026minus;80\u0026deg;C.Enzyme-linked immunosorbent assays (ELISAs) were used to quantify plasma levels of lipopolysaccharide (LPS), factor VIII (FVIII), von Willebrand factor (vWF), soluble P-selectin (sPS), soluble CD40 ligand (sCD40L), and ADAMTS13 (Jiangsu Jingmei Biotechnology Co., Ltd.).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e2.1 Comparison of Baseline Characteristics Between Groups\u003c/p\u003e\n\u003cp\u003ePVT patients exhibited significantly higher fibrinogen (FIB) and D-dimer levels compared to non-PVT patients (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), indicating poorer liver function and a hypercoagulable state in the PVT group (Table\u0026nbsp;1).\u003c/p\u003e\n\u003cp\u003eTable 1. Comparison of Baseline Characteristics Between PVT and Non-PVT Groups\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003ctable id=\"Taba\" border=\"1\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePVT group (n\u0026thinsp;=\u0026thinsp;16)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNon-PVT group (n\u0026thinsp;=\u0026thinsp;24)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003estatistic\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e56.31\u0026thinsp;\u0026plusmn;\u0026thinsp;10.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e57.46\u0026thinsp;\u0026plusmn;\u0026thinsp;13.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003et\u003c/em\u003e=-0.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.770\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGender [n(%)]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026chi;\u0026sup2;\u003c/em\u003e=0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.792\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ewoman\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (37.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10 (41.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eman\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10 (62.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14 (58.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBMI(kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24.36\u0026thinsp;\u0026plusmn;\u0026thinsp;3.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25.93\u0026thinsp;\u0026plusmn;\u0026thinsp;4.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026chi;\u0026sup2;\u003c/em\u003e=1.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.238\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDrinking history\u003c/p\u003e\n \u003cp\u003e[ n (%)]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026chi;\u0026sup2;\u003c/em\u003e=0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.685\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking history\u003c/p\u003e\n \u003cp\u003e[n (%)]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026chi;\u0026sup2;\u003c/em\u003e=0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.833\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ecause of disease\u003c/p\u003e\n \u003cp\u003e[n (%)]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.681\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eviral\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5(31.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10(41.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ealcoholic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(12.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4(16.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eautoimmunity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0(0.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(8.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrimary biliary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(6.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(4.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eother\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8(50.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7(29.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMELD评分\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.59 (6.48, 9.93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.75 (7.69, 11.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eZ\u003c/em\u003e=-1.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.155\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWBC(10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.02 (3.25, 7.36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.94 (2.67, 5.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eZ\u003c/em\u003e=-1.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.255\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNEUT(10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.46 (2.45, 5.82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.73 (1.54, 3.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eZ\u003c/em\u003e=-1.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.129\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMONO(109/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.29 (0.19, 0.57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.22 (0.15, 0.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eZ\u003c/em\u003e=-1.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.246\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLYM(109/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.61 (0.51, 0.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.74 (0.51, 0.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eZ\u003c/em\u003e=-0.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.525\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHb(g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e97.12\u0026thinsp;\u0026plusmn;\u0026thinsp;31.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e85.33\u0026thinsp;\u0026plusmn;\u0026thinsp;20.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003et\u003c/em\u003e=-1.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.200\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePLT(109/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e101.00 (48.25, 233.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e75.50 (37.75, 100.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eZ\u003c/em\u003e=-1.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.073\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eALB(g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33.59\u0026thinsp;\u0026plusmn;\u0026thinsp;4.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34.90\u0026thinsp;\u0026plusmn;\u0026thinsp;6.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003et\u003c/em\u003e=-0.70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.485\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAST(U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e37.35 (23.00, 55.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28.75 (21.45, 37.53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eZ\u003c/em\u003e=-0.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.334\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eALT(U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26.80 (15.07, 49.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19.35 (11.15, 31.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eZ\u003c/em\u003e=-1.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.199\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePT(s)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13.05 (12.50, 14.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13.35 (12.80, 15.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eZ\u003c/em\u003e=-0.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.327\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePTA(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e78.81\u0026thinsp;\u0026plusmn;\u0026thinsp;14.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e72.80\u0026thinsp;\u0026plusmn;\u0026thinsp;17.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003et\u003c/em\u003e=--1.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.268\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eINR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.15 (1.06, 1.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.17 (1.10, 1.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eZ\u003c/em\u003e=-1.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.189\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAPTT(s)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29.25 (26.62, 31.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26.95 (25.12, 27.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eZ\u003c/em\u003e=-1.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.129\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFIB(g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.46 (1.73, 3.48)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.00 (1.25, 2.40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eZ\u003c/em\u003e=-2.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.030\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTT(s)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17.95 (17.20, 19.15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18.35 (17.28, 19.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eZ\u003c/em\u003e=-0.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.720\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eD-dimer (mg/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.85 (3.10, 8.96)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.50 (0.59, 3.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eZ\u003c/em\u003e=-3.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eNote:BMI: Body Mass Index;MELD: Model for End-Stage Liver Disease;WBC: White Blood Cell Count;NEUT: Neutrophil Count;MONO: Monocyte Count;LYM: Lymphocyte Count;Hb: Hemoglobin;PLT: Platelet Count;ALB: Albumin;AST: Aspartate Aminotransferase;ALT: Alanine Aminotransferase;PT: Prothrombin Time;PTA: Prothrombin Time Activity;INR: International Normalized Ratio;APTT: Activated Partial Thromboplastin Time;FIB: Fibrinogen;TT: Thrombin Time;P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 indicates statistical significance.\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003e2.2 Comparison of Endothelial Injury and Platelet Activation Markers\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003e2.1 Comparison Between Portal and Peripheral Venous Levels in All Patients\u003cbr\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003eIn 40 cirrhotic patients, portal venous concentrations of LPS, FVIII, vWF, sPS, and sCD40L were significantly higher than peripheral venous levels, while ADAMTS13 was markedly lower (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). These findings indicate a concentration gradient disparity between portal and peripheral compartments, reflecting localized endothelial injury and platelet activation in the portal circulation (Table\u0026nbsp;2; Fig.\u0026nbsp;1).\u003c/p\u003e\n\u003cp\u003eTable 2. Comparison of Endothelial/Platelet Markers in Portal vs. Peripheral Venous Blood\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003ctable id=\"Tabb\" border=\"1\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePortal vein\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;40)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePeripheral venous\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;40)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003estatistic\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLPS(pg/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e85.37\u0026thinsp;\u0026plusmn;\u0026thinsp;25.72*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e77.50\u0026thinsp;\u0026plusmn;\u0026thinsp;24.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003et\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFⅧ(pg/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e86.54 (75.26, 93.55) *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e78.03 (64.94, 88.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eZ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;76.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003evWF(pg/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e51.61 (44.37, 65.47) *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49.29 (40.25, 61.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eZ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;116.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eADAMTS-13(pg/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e70.15 (56.41, 83.75) *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e77.47 (66.12, 87.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eZ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;671.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003esPS(pg/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.83 (3.57, 4.66) *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.61 (3.08, 4.40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eZ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;42.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003esCD40L(pg/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.01 (2.62, 4.05) *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.69 (2.37, 3.74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eZ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;17.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e*Significant difference (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\n\u003cp\u003e2.2.2 Comparison of portal vein and peripheral vein endothelial injury and platelet activation markers in patients with liver cirrhosis PVT\u003c/p\u003e\n\u003cp\u003eIn 16 cirrhotic patients with PVT, portal venous concentrations of LPS, FVIII, vWF, sPS, andsCD40L were significantly higher than peripheral venous levels, whileADAMTS13 was markedly lower (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). These findings confirm a concentration gradient disparity between portal and peripheral compartments in PVT patients, suggesting localized endothelial dysfunction and platelet activation (Table 3; Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eTable 3. Comparison of Endothelial and Platelet Markers in Portal and Peripheral Venous Blood in PVT Patients\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003ctable id=\"Tabc\" border=\"1\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePortal vein\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;16)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePeripheral venous\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;16)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003estatistic\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLPS(pg/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e106.29\u0026thinsp;\u0026plusmn;\u0026thinsp;17.45*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e96.71\u0026thinsp;\u0026plusmn;\u0026thinsp;15.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003et\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFⅧ(pg/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e93.67 (89.15, 107.56) *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e87.27 (75.55, 99.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eZ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;3.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003evWF(pg/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e71.72\u0026thinsp;\u0026plusmn;\u0026thinsp;24.01*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e62.39\u0026thinsp;\u0026plusmn;\u0026thinsp;19.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003et\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eADAMTS-13(pg/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e57.99\u0026thinsp;\u0026plusmn;\u0026thinsp;22.20*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e62.90\u0026thinsp;\u0026plusmn;\u0026thinsp;23.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003et\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.781\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.014\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003esPS(pg/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.04 (3.73, 11.60) *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.65 (3.60, 10.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eZ\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003esCD40L(pg/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.77 (2.85, 11.45) *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.29 (2.63, 11.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eZ\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e*Significant difference (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\n\u003cp\u003e2.2.3 Comparison of Endothelial Injury and Platelet Activation Markers Between PVT and Non-PVT Patients\u003c/p\u003e\n\u003cp\u003eIn cirrhotic patients with PVT, portal venous concentrations of LPS, FVIII, vWF, sPS, and sCD40L were significantly higher compared to non-PVT patients, while ADAMTS13 levels were markedly lower (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). These findings demonstrate distinct gradients of endothelial injury and platelet activation markers in the portal circulation of PVT patients (Table 4; Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eTable 4. Comparison of Endothelial and Platelet Markers in Portal Venous Blood Between PVT and Non-PVT Groups\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003ctable id=\"Tabd\" border=\"1\" class=\"fr-table-selection-hover\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePVT group\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;16)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNon-PVT group\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;24)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003estatistic\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLPS(pg/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e102.60 (97.03, 112.56) *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e75.59 (60.09, 83.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eZ\u003c/em\u003e=-4.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFⅧ(pg/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e93.67 (89.15, 107.56) *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e78.02 (61.04, 88.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eZ\u003c/em\u003e=-3.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003evWF(pg/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e70.15 (52.50, 79.16) *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e45.98 (42.80, 53.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eZ\u003c/em\u003e=-3.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eADAMTS-13(pg/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e57.16 (51.38, 76.71) *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e74.43 (65.62, 87.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eZ\u003c/em\u003e=-2.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.020\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003esPS(pg/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6.04 (3.73, 11.60) *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3.76 (3.27, 3.94)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eZ\u003c/em\u003e=-3.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003esCD40L(pg/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7.77 (2.85, 11.45) *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.71 (2.50, 3.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eZ\u003c/em\u003e=-3.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e*Significant difference (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\n\u003cp\u003e2.3 Correlation Analysis Between Portal LPS Levels and Endothelial/Platelet Markers in 40 Cirrhotic Patients\u003c/p\u003e\n\u003cp\u003eIn 40 cirrhotic patients, portal LPS concentration showed significant positive correlations with FVIII (R\u0026sup2; = 0.47, P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), vWF (R\u0026sup2; = 0.37, P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), sPS (R\u0026sup2; = 0.27, P\u0026thinsp;=\u0026thinsp;0.006), and sCD40L (R\u0026sup2; = 0.27, P\u0026thinsp;=\u0026thinsp;0.0007). No correlation was observed between LPS and ADAMTS13 (R\u0026sup2; = 0.068, P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Additionally, vWF levels exhibited a negative correlation with ADAMTS13 (R\u0026sup2; = 0.15, P\u0026thinsp;=\u0026thinsp;0.0139) (Fig. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study demonstrated that cirrhotic patients with portal vein thrombosis (PVT) exhibit a significant gradient of endothelial injury and platelet activation markers in the portal venous system compared to peripheral circulation, with markedly elevated levels in the portal vein. Further analysis revealed that this phenomenon was closely associated with lipopolysaccharide (LPS). Cirrhosis, characterized by severe hepatic architectural distortion and nodular regeneration, compresses hepatic sinusoids and vasculature, increasing intrahepatic resistance and culminating in portal hypertension. Portal hypertension profoundly impacts intestinal permeability, gut microbiota balance, and bacterial translocation. By reducing mucosal blood flow and promoting neovascularization, cirrhotic portal hypertension induces intestinal ischemia and edema, disrupting the intestinal barrier and facilitating bacterial-derived LPS translocation into the portal circulation\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e. Once in the circulatory system, LPS interacts with Toll-like receptors (Toll-like receptors, TLRs) and triggers a series of pathophysiological changes associated with the formation of PVT. On one hand, LPS binds to TLRs expressed on hepatocytes and immune cells. The activation of these cells triggers the release of large amounts of inflammatory mediators, chemokines, vasoactive substances, adhesion molecules, and reactive oxygen species (Reactive Oxygen Species, ROS) [14], leading to systemic inflammatory responses, promoting hepatostellate cell proliferation, and the progression of liver cirrhosis[15]. On the other hand, LPS binds to TLRs expressed on vascular endothelial cells, platelets, and neutrophils, promoting a hypercoagulable state and PVT[16]in the context of liver cirrhosis.\u003c/p\u003e\u003cp\u003eVon Willebrand factor (vWF), a marker of endothelial dysfunction\u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e, and factor VIII (FVIII), a key indicator of hypercoagulability in cirrhosis\u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e, play critical roles in hemostasis and thrombogenesis. This study demonstrated that FVIII levels in the portal vein are significantly elevated in cirrhotic patients compared to peripheral venous levels, consistent with Delahousse et al.\u0026rsquo;s findings\u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e. These results indicate a sustained prothrombotic state within the portal circulation of cirrhotic patients\u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e, where enhanced FVIII activity represents a major mechanism driving portal hypercoagulability.Carnevale et al.\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e demonstrated that serum levels of LPS, FVIII, and vWF are significantly elevated in cirrhotic patients compared to non-cirrhotic controls, with strong positive correlations between LPS and both FVIII and vWF. In vitro studies further revealed that LPS stimulates Weibel-Palade body (WPB) formation and secretion via TLR4 signaling, prompting human umbilical vein endothelial cells (HUVECs) to release FVIII and vWF. Consistent with these findings, our study revealed markedly higher portal venous levels of LPS, FVIII, and vWF in cirrhotic PVT patients compared to peripheral circulation, establishing a concentration gradient disparity. Moreover, the significant correlations between LPS, FVIII, and vWF in portal blood align with prior evidence\u003csup\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e, underscoring the role of LPS as a potential trigger for endothelial injury and hypercoagulability in cirrhotic PVT.ADAM (A Disintegrin and Metalloproteinase) and its subfamily ADAMTS (ADAM with thrombospondin motifs) are proteases predominantly synthesized by hepatic stellate cells and play critical regulatory roles in hemostasis. ADAMTS-13, a key member of this subfamily, acts as the von Willebrand factor-cleaving protease (vWFCP), cleaving ultra-large von Willebrand factor multimers (UL-vWFM) into smaller, less thrombogenic fragments\u003csup\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e. In cirrhosis, reduced ADAMTS-13 activity or levels lead to accumulation of UL-vWFM, which stabilize platelet aggregates and promote thrombus formation. This dysregulation is compounded by vWF\u0026rsquo;s role as an FVIII carrier; activated UL-vWFM enhances FVIII stability and activity, amplifying the intrinsic coagulation pathway .Lancellotti et al.\u003csup\u003e[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e demonstrated that ADAMTS-13 activity is significantly lower in cirrhotic PVT patients compared to non-PVT controls, and this deficiency correlates independently with PVT risk\u003csup\u003e[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e. Tomasz and colleagues further validated that low serum ADAMTS-13 levels serve as a robust predictor of PVT in decompensated cirrhosis, independent of Child-Pugh or MELD scores\u003csup\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e. Our study extends these findings by revealing markedly reduced ADAMTS-13 levels in the portal venous system of cirrhotic PVT patients. Notably, portal vWF levels exhibited a significant inverse correlation with ADAMTS-13, while vWF positively correlated with LPS, underscoring ADAMTS-13\u0026rsquo;s pivotal role in PVT pathogenesis. ADAMTS-13 primarily exerts its influence by modulating vWF levels, further highlighting its potential role in the pathological mechanisms of PVT in liver cirrhosis. As the condition of patients with liver cirrhosis deteriorates, the enzymatic activity of ADAMTS-13 produced by hepatic stellate cells gradually diminishes, leading to a sustained decline in ADAMTS-13 levels\u003csup\u003e[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e. Inflammatory cytokines released under the pathophysiological state of liver cirrhosis may affect the balance between the number of ULVWF polymers released by endothelial cells and the rate at which ADAMTS-13 cleaves ULVWF. Therefore, in the context of endotoxemia and inflammation associated with decompensated liver cirrhosis, the decrease in ADAMTS-13 levels is likely to contribute to portal vein thrombosis in patients with liver cirrhosis\u003c/p\u003e\u003cp\u003ePatients with liver cirrhosis are more prone to thrombocytopenia due to various factors such as reduced platelet production, abnormal distribution, and increased destruction, thereby increasing the risk of bleeding. However, some studies have indicated that\u003csup\u003e[\u003cspan additionalcitationids=\"CR27\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/sup\u003e, the platelets in patients with liver cirrhosis are in an activated state, which is not influenced by the number of platelets and is closely associated with endotoxemia. Endotoxemia leads to elevated levels of LPS in circulation, which can activate Toll-like receptor 4 (TLR4) on the surface of platelets, enhancing their responsiveness to agonists (such as collagen and ADP), promoting platelet aggregation and thrombus formation\u003csup\u003e[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/sup\u003e. Additionally, LPS can activate Toll-like receptor 2 (TLR2) on the surface of platelets, increasing the release of α granules and dense granules, facilitating interaction between platelets and vascular endothelial cells, further promoting platelet-dependent thrombus formation \u003csup\u003e[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/sup\u003eValeria et al. \u003csup\u003e[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/sup\u003edemonstrated that levels of LPS, soluble CD40 ligand (sCD40L), and soluble P-selectin (sPS) are significantly elevated in the systemic circulation of cirrhotic patients, providing the first direct evidence linking LPS to platelet activation and thrombotic complications in cirrhosis. Their in vitro studies further revealed that LPS activates platelets via Toll-like receptor 4 (TLR4), enhancing platelet reactivity to agonists such as collagen and ADP. This finding aligns with our observation of elevated sCD40L and sPS in the portal venous system of cirrhotic PVT patients, underscoring their role as biomarkers of thrombotic risk. The role of LPS-mediated oxidative stress in platelet activation has emerged as a critical driver of portal vein thrombosis (PVT) in cirrhosis\u003csup\u003e[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/sup\u003e. Our previous studies demonstrated that soluble NOXA2 derivative (sNOX2-dp), a marker of NADPH oxidase (NOX2) activation, is significantly elevated in the portal venous system of cirrhotic PVT patients compared to non-PVT controls, with a strong positive correlation to LPS levels. These findings align with Stefania et al.\u0026rsquo;s work\u003csup\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/sup\u003e, which showed systemic increases in sNOX2-dp, sPS, and sCD40L in cirrhotic patients, further highlighting the interdependence of oxidative stress and platelet activation. This study further reveals that sCD40L and sPS levels in the portal venous system of cirrhotic PVT patients are significantly elevated compared to peripheral venous levels, with strong positive correlations to LPS concentrations. These findings underscore the enhanced platelet activation in the portal circulation, particularly in PVT patients, and highlight the central role of LPS-mediated oxidative stress in driving this pathology.\u003c/p\u003e\u003cp\u003eThis study provides further evidence supporting the heightened significance of endothelial injury and platelet activation in the portal venous circulation of cirrhotic patients with portal vein thrombosis (PVT), both of which are closely associated with lipopolysaccharide (LPS). These findings suggest that modulating LPS levels may represent a therapeutic strategy to reduce PVT risk in cirrhotic patients. Dynamic monitoring of endothelial injury and platelet activation markers, coupled with timely intervention to suppress platelet hyperactivity, could serve as critical therapeutic targets for managing PVT in cirrhosis.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eTIPS \u0026nbsp; \u0026nbsp; \u0026nbsp; Transjugular intrahepatic portosystemic shunt\u003c/p\u003e\n\u003cp\u003ePVT \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Portal Vein Thrombosis\u003c/p\u003e\n\u003cp\u003ePAMPs \u0026nbsp; \u0026nbsp; \u0026nbsp;Pathogen-Associa ted Molecular Patterns\u003c/p\u003e\n\u003cp\u003eLPS \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Lipopolysaccharide\u003c/p\u003e\n\u003cp\u003eTLR4 \u0026nbsp; \u0026nbsp; \u0026nbsp; Toll like receptor 4\u003c/p\u003e\n\u003cp\u003eFⅧ \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Human Coagulation Factor Ⅷ\u003c/p\u003e\n\u003cp\u003evWF \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; von Willebrand Factor\u003c/p\u003e\n\u003cp\u003esPS \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;soluble P-selectin\u003c/p\u003e\n\u003cp\u003esCD40L \u0026nbsp; \u0026nbsp; \u0026nbsp;soluble CD40 Ligand\u003c/p\u003e\n\u003cp\u003eTLRs \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Toll-like receptors\u003c/p\u003e\n\u003cp\u003eROS \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Reactive Oxygen Species\u003c/p\u003e\n\u003cp\u003eWPB \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Weibel-Palade body\u003c/p\u003e\n\u003cp\u003eHUVEC \u0026nbsp; \u0026nbsp; \u0026nbsp;Human Umbilical Vein Endothelial Cells\u003c/p\u003e\n\u003cp\u003evWFCP \u0026nbsp; \u0026nbsp; \u0026nbsp;von Willebrand factor-cleaving protease\u003c/p\u003e\n\u003cp\u003eUL-VWFM \u0026nbsp; Ultra-Large von Willebrand Factor Multimers\u003c/p\u003e\n\u003cp\u003eIL-8 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Interleukin-8\u003c/p\u003e\n\u003cp\u003eIL-6 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Interleukin-6\u003c/p\u003e\n\u003cp\u003eTNF-\u0026alpha; \u0026nbsp; \u0026nbsp; \u0026nbsp; Tumor Necrosis Factor-\u0026alpha;\u003c/p\u003e\n\u003cp\u003esNOX2-dp \u0026nbsp; \u0026nbsp;soluble NOXA2 derivative\u003c/p\u003e\n\u003cp\u003esGPVI \u0026nbsp; \u0026nbsp; \u0026nbsp; soluble glycoprotein VI\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eXuXu Yang was responsible for conception , design of study , drafting of manuscript and critical revision. Ping Qi was responsible for the\u0026nbsp;data analysis and/or interpretation. Wei Sang, Pingping Li, Yueqin Li and Yun Bai were responsible for approvaling of final version of manuscript. The authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by in 2022, the government will support the Training project of clinical medical talents, subject number: 20220017.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe original data generated in the course of the study are from Hebei Provincial People\u0026apos;s Hospital. (We are in the process of uploading the raw data to the database, but it will take some time for the upload to be successful)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Ethics Committee of Hebei Provincial People\u0026apos;s Hospital, and every participant signed informed consent. The written informed consent of all subjects was obtained following the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eQi Xingshun Y, Ling. 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Thromb Haemost. 2009;102(1):97\u0026ndash;110.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-gastroenterology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmge","sideBox":"Learn more about [BMC Gastroenterology](http://bmcgastroenterol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmge/default.aspx","title":"BMC Gastroenterology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Liver cirrhosis, Portal vein thrombosis, Endothelial injury, Platelet activation, Coagulation abnormalities, LPS","lastPublishedDoi":"10.21203/rs.3.rs-6794559/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6794559/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study aims to investigate the mechanisms of coagulation abnormalities in portal vein thrombosis (PVT) in patients with liver cirrhosis by collecting portal and peripheral venous blood samples through interventional methods. The differences in lipopolysaccharide (LPS), Factor VIII (FⅧ), von Willebrand factor (vWF), a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13), soluble P-selectin (sPS), and soluble CD40 ligand (sCD40L) levels between patients with liver cirrhosis and PVT and those without PVT were analyzed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods：\u003c/strong\u003eA total of 40 patients diagnosed with liver cirrhosis and undergoing transjugular intrahepatic portosystemic shunt (TIPS) treatment at Hebei Provincial People's Hospital from April 2022 to October 2024 were enrolled. According to the diagnostic criteria for PVT in liver cirrhosis, patients were divided into the PVT group (n=16) and the non-PVT group (n=24). General patient information and relevant laboratory tests were collected, and differences in age, gender, etiology, medical history, body mass index (BMI), and laboratory test indicators between the two groups were compared. Portal and peripheral venous blood samples were collected through TIPS, and LPS, FⅧ, vWF, ADAMTS13, sPS, and sCD40L concentrations were measured using ELISA. The levels of these indicators in the portal and peripheral veins were compared between the PVT and non-PVT groups, and correlation analyses were performed between LPS and FⅧ, vWF, ADAMTS13, sPS, and sCD40L.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults：\u003c/strong\u003e1.There were no significant differences between the PVT and non-PVT groups in age, gender, BMI, etiology, smoking history, alcohol consumption history, diabetes history, Model for End-Stage Liver Disease (MELD) score, white blood cell (WBC) count, neutrophil (NEUT) count, monocyte (MONO) count, lymphocytes (L), hemoglobin (Hb) level, platelet (PLT) count, albumin (ALB) level, alanine aminotransferase (ALT) level, aspartate aminotransferase (AST) level, prothrombin time (PT), prothrombin activity (PTA), international normalized ratio (INR), activated partial thromboplastin time (APTT), and thrombin time (TT) (P\u0026gt;0.05). However, there were significant differences between the two groups in the fibrinogen (FIB) level, and D-dimer level (P\u0026lt;0.05)；2.In patients with liver cirrhosis, the levels of LPS, FⅧ, vWF, sPS, and sCD40L in portal venous blood were higher than those in peripheral venous blood, while the level of ADAMTS13 was lower. These differences were statistically significant (P\u0026lt;0.05). Similar differences were observed in patients with liver cirrhosis and PVT. Furthermore, the levels of LPS, FⅧ, vWF, sPS, and sCD40L in portal venous blood were higher in patients with liver cirrhosis and PVT than in those without PVT, while the level of ADAMTS13 was lower. These differences were also statistically significant (P\u0026lt;0.05). Additionally, among the 40 patients with liver cirrhosis, FⅧ, vWF, sPS, and sCD40L were significantly correlated with LPS (P\u0026lt;0.05), while there was no significant correlation between ADAMTS13 and LPS (P\u0026gt;0.05). A significant correlation was observed between vWF and ADAMTS13 (P\u0026lt;0.05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e Endotoxemia in patients with portal vein thrombosis in cirrhosis can activate the endothelial damage and platelet activation mechanism of the portal vein system, and then lead to local coagulation dysfunction, which plays an important role in the formation of portal vein thrombosis in cirrhosis.\u003c/p\u003e","manuscriptTitle":"Study on the Mechanisms of Coagulation Abnormalities in Portal Vein Thrombosis in Patients with Liver Cirrhosis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-22 16:14:58","doi":"10.21203/rs.3.rs-6794559/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"296020048699445441578542430140807678018","date":"2025-08-07T05:43:03+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-15T09:22:28+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-09T07:38:59+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-06-19T07:02:50+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-06-18T10:32:43+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Gastroenterology","date":"2025-06-18T10:09:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-gastroenterology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmge","sideBox":"Learn more about [BMC Gastroenterology](http://bmcgastroenterol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmge/default.aspx","title":"BMC Gastroenterology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"fbdb6fbb-267d-4e54-804e-fb9bddffa219","owner":[],"postedDate":"July 22nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-07-22T16:14:58+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-22 16:14:58","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6794559","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6794559","identity":"rs-6794559","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}
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