Exploration of Systemic and Portal Hemostasis in Patients Undergoing Transjugular Intrahepatic Portosystemic Shunt Placement (PORTHEMOST)

Portal vein thrombosis is defined as non-tumoural obstruction of the portal vein or one of its branches. Its incidence is 0.7 to 2.7 per 100,000 patient-years in the general population, and 4.6 per 100 patient-years in patients with cirrhosis. Histological modificaitions fo the portal vein wall and haemostatic changes have been described in cirrhotic patients. The contribution of these changes, both systemic and local, to the development of portal vein thrombosis is debated. One of the hypotheses put forward on the genesis of portal vein thrombosis is as follows: certain bacterial translocations from the digestive tract, promoted by portal hypertension, contribute to endothelial activation resulting in the release of von Willebrand factor and factor VIII, as well as platelet activation and the coagulation cascade, which is dysregulated by cirrhosis and underlying changes in haemostatic balance. Inflammatory phenomena and NETosis may also be involved. Studies suggest that cirrhotic patients have lesions of the glycocalyx located in the portal area, which may be involved in the development of portal vein thrombosis. Patients with cirrhosis may benefit from the placement of a transjugular intrahepatic portosystemic shunt (TIPS). During the TIPS placement procedure, blood is drawn from the internal jugular vein and the portal vein, allowing for parallel biological analyses. The assumption of this study is that haemostasis and inflammation are disrupted differently at the systemic and portal levels in cirrhotic patients.

Study Overview

• Status: Recruiting
• Conditions: Liver Cirrhosis; Portal Hypertension

Detailed Description

Portal vein thrombosis is defined as non-tumoural obstruction of the portal vein or one of its branches. Its incidence is 0.7 to 2.7 per 100,000 patient-years in the general population, and 4.6 per 100 patient-years in patients with cirrhosis. Portal vein thrombosis associated with cirrhosis, which is most often non-occlusive (70%), is characterised by histological changes in the portal vein wall and the presence of an intraluminal thrombus.

In cirrhotic patients, histological changes are described at the portal level. In response to portal hypertension, the calibre of the portal vein, where circulation is at low pressure and high compliance, increases. In response to this mechanical stress, intimal hypertrophy and fibroblast proliferation are observed. In cases of portal vein thrombosis, these changes are more pronounced. Changes in haemostatic balance are also observed in these patients. Thrombocytopenia and decreased synthesis of coagulation factors on the one hand, and decreased coagulation cascade and fibrinolytic regulatory factors on the other, contribute to creating a new fragile haemostatic balance. The contribution of these changes, both systemic and local, to the development of portal vein thrombosis is debated.

One of the hypotheses put forward on the genesis of portal vein thrombosis is as follows: certain bacterial translocations from the digestive tract, promoted by portal hypertension, contribute to endothelial activation resulting in the release of von Willebrand factor (VWF) and factor VIII, as well as platelet activation and the coagulation cascade, which is dysregulated by cirrhosis and underlying changes in haemostatic balance.

This hypothesis is supported by several studies showing that cirrhotic patients have higher portal than systemic levels of VWF, factor VIII and lipopolysaccharides. Inflammatory phenomena and NETosis may also be involved.

The vascular endothelial surface is covered by the glycocalyx, with antithrombotic and anti-inflammatory effects that regulates vascular permeability. The endothelial glycocalyx has three major components: proteoglycans binding to the endothelial membrane, sulphated glycosaminoglycans bound laterally to proteoglycans, and plasma proteins. Studies suggest that cirrhotic patients have lesions of the glycocalyx located in the portal area, which may be involved in the development of portal vein thrombosis. Patients with cirrhosis may benefit from the placement of a transjugular intrahepatic portosystemic shunt (TIPS).

During the TIPS placement procedure, blood is drawn from the internal jugular vein and the portal vein, allowing for parallel biological analyses.

The assumption of this study is that haemostasis and inflammation are disrupted differently at the systemic and portal levels in cirrhotic patients. To our knowledge, studies conducted to date have not investigated haemostasis under flow conditions, which are more physiological than static investigations.

• Study Type: Observational
• Enrollment (Estimated): 45

Contacts and Locations

• Study Contact: Name: Stéphanie ROULLET stephanie.roullet@aphp.fr, PhD; Phone Number: +33 145596949; Email: stephanie.roullet@aphp.fr

Study Locations

• France
  • Villejuif, France, 94800
    • Recruiting
    • Hôpital Paul Brousse
    • Contact: STEPHANIE ROULLET, PhD; Phone Number: +33 145596949; Email: stephanie.roullet@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with cirrhosis, regardless of the underlying cause, undergoing TIPS placement, regardless of the indication.

Description

Inclusion Criteria:

• Adult patients (aged ≥18 years) covered by a social security scheme or entitled beneficiaries
• Patients followed for a cirrhotic condition at Paul Brousse Hospital and undergoing placement of a TIPS (transjugular intrahepatic portosystemic shunt)

Exclusion Criteria:

• Patient unwilling to participate in the study
• Patient with a contraindication to TIPS placement
• Patient with a known hemostatic disorder unrelated to cirrhosis
• Patient receiving treatment that interferes with hemostasis and has not been discontinued for the procedure
• Patient receiving systemic corticosteroid therapy
• Patient under legal protection
• Patient not covered by a social security scheme

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve (AUC) of primary hemostasis assessed by T-TAS®01 at 10 minutes	The primary outcome measure is the area under the curve (AUC) obtained at 10 minutes of perfusion during the assessment of primary hemostasis using the T-TAS®01 microfluidic system. Measurements are performed with PL chips coated with collagen. Under these conditions, thrombus formation is dependent on von Willebrand factor, allowing evaluation of primary hemostasis at the systemic and portal levels in patients with cirrhosis.	At 10 minutes of perfusion during the T-TAS®01 primary hemostasis assessment procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to reach 10 kPa above baseline pressure in the T-TAS®01 system	Time required to reach a pressure of 10 kPa above baseline during perfusion in the T-TAS®01 microfluidic system, measured on systemic and portal blood samples	At the time of TIPS placement
Time to reach 60 kPa above baseline pressure in the T-TAS®01 system	Time required to reach a pressure of 60 kPa above baseline during perfusion in the T-TAS®01 microfluidic system, measured on systemic and portal blood samples	At the time of TIPS placement
Conventional coagulation parameters at systemic and portal levels	Prothrombin time, activated partial thromboplastin time ratio, factor V, fibrinogen (Clauss method), antithrombin, factor VIII, von Willebrand factor antigen and activity, and ADAMTS-13 activity measured in systemic and portal blood samples	At the time of TIPS placement
Fibrinolysis parameters at systemic and portal levels	Tissue plasminogen activator antigen and activity, plasminogen activator inhibitor-1 antigen and activity, D-dimers, protease nexin-1, and global fibrinolytic capacity measured in systemic and portal blood samples	At the time of TIPS placement
Complete blood count parameters at systemic and portal levels	Complete blood count parameters including hemoglobin, hematocrit, leukocytes, and platelet count measured in systemic and portal blood samples	At the time of TIPS placement
ROTEM® coagulation parameters at systemic and portal levels	ROTEM® EXTEM and INTEM parameters including clotting time, clot formation time, amplitude at 5 minutes, and maximum clot firmness measured in systemic and portal blood samples	At the time of TIPS placement
Thrombin generation parameters at systemic and portal levels	Thrombin generation test parameters including lag time, time to peak, peak thrombin, endogenous thrombin potential, velocity index, and end of test time, assessed with and without thrombomodulin in systemic and portal samples	At the time of TIPS placemen
Inflammatory biomarkers at systemic and portal levels	Albumin, C-reactive protein, interleukin-6, and lipopolysaccharides measured in systemic and portal blood samples	At the time of TIPS placement
Endothelial and glycocalyx biomarkers at systemic and portal levels	Angiopoietin-1, angiopoietin-2, glycosaminoglycans, heparan sulfate, syndecan, soluble thrombomodulin, and soluble P-selectin measured in systemic and portal blood samples	At the time of TIPS placement
Markers of thrombo-inflammation and NETosis at systemic and portal levels	Cell-free DNA, citrullinated histone-3, DNA-histone-3 complexes, and DNase activity measured in systemic and portal blood samples	At the time of TIPS placement
Child-Pugh score	Assessment of liver disease severity using the Child-Pugh score (range 5-15, higher scores indicate more severe liver disease), measured prior to TIPS placement	Prior to TIPS placement
MELD score	Assessment of liver disease severity using the Model for End-Stage Liver Disease (MELD) score, measured prior to TIPS placement	Prior to TIPS placement
Portal-systemic pressure gradient	Measurement of the porto-systemic pressure gradient prior to TIPS placement	Prior to TIPS placement
Occurrence of TIPS thrombosis at Day 90	Occurrence of partial or complete thrombosis of the TIPS or a portal vein branch within 90 days after TIPS placement	Up to 90 days after TIPS placement
Need for TIPS revision or recalibration at Day 90	Need for TIPS revision or recalibration within 90 days after TIPS placement	Up to 90 days after TIPS placement
Major clinical events at Day 90	Occurrence of liver transplantation, gastrointestinal bleeding, or TIPS infection within 90 days after TIPS placement	Up to 90 days after TIPS placement

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): March 9, 2026
• Primary Completion (Estimated): June 9, 2027
• Study Completion (Estimated): June 9, 2027

Study Registration Dates

• First Submitted: January 19, 2026
• First Submitted That Met QC Criteria: February 26, 2026
• First Posted (Actual): February 27, 2026

Study Record Updates

• Last Update Posted (Actual): April 21, 2026
• Last Update Submitted That Met QC Criteria: April 20, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: portal hypertension; Blood Coagulation; liver cirrhosis; Fibrinolysis; Endothelial Dysfunction; Transjugular Intrahepatic Portosystemic Shunt; von Willebrand Factor; Primary Hemostasis; Thromboinflammation; Portal Circulation
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Digestive System Diseases; Inflammation; Hematologic Diseases; Liver Diseases; Embolism and Thrombosis; Blood Coagulation Disorders; Fibrosis; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Thromboinflammation; Thrombosis; Liver Cirrhosis; Hypertension, Portal
• Other Study ID Numbers: APHP251320; 2025-A02001-48 (Other Identifier: IDRCB)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No