Portal vein thrombosis and hemostatic alterations in patients with advanced liver diseases

    Research output: ThesisThesis fully internal (DIV)

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    Abstract

    In patients with liver diseases, the liver has a reduced capacity to produce pro- and antihemostatic proteins. This results in a rebalanced hemostatic system, which remains stable in patients with stable liver diseases but can be fragile in those with additional disease complications, such as inflammation or renal failure. Although liver diseases were long associated with an increased risk of bleeding, hemostasis-related bleeding is rare in patients with liver diseases. With increasing insights, it becomes evident that patients with liver diseases have an elevated risk of thrombotic complications, with portal vein thrombosis being the primary concern. The pathophysiology of portal vein thrombosis is not fully understood. The studies described in this thesis aimed to gain more insights into the development of portal vein thrombosis in patients with chronic liver diseases. The results showed that, in most patients with portal vein thrombosis, there is no classical thrombus consisting of fibrin, platelets, and red blood cells. Instead, the obstruction of the portal vein is caused by thickening of the vessel wall. Portal vein thrombosis may therefore be a misnomer and might be more accurately termed as 'portal vein stenosis' or 'portal vein intima hyperplasia.' Additionally, we investigated whether blood in the portal vein of liver patients has locally elevated levels of markers of activation of coagulation or inflammation, due to drainage from the intestines. This could potentially lead to a locally increased risk of thrombosis. However, no differences were found in samples taken from the systemic circulation and the portal vein. Furthermore, there was no correlation between elevated levels of markers of activation of coagulation or inflammation in the systemic circulation and the development of portal vein thrombosis in patients with chronic liver diseases. Factors related to the development of portal vein thrombosis were factors that are associated with portal hypertension and changes in portal blood flow. The findings described may explain why treatment with anticoagulants is not always effective in the treatment of portal vein thrombosis in cirrhosis. The insights described in this thesis pave the way for exploring new treatment strategies. Future studies should focus on investigating safe and effective pharmacotherapeutic interventions for the prevention and treatment of portal vein thrombosis or portal vein intima hyperplasia in patients with chronic liver diseases.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    Supervisors/Advisors
    • Lisman, Ton, Supervisor
    • Porte, Robert, Supervisor
    Award date17-Jan-2024
    Place of Publication[Groningen]
    Publisher
    Print ISBNs978-94-6483-654-7
    DOIs
    Publication statusPublished - 2024

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