Pathophysiology and management of bleeding and thrombosis in patients with liver disease

Abstract

Patients with liver disease often develop complex changes in their haemostatic system. Frequently observed changes include thrombocytopaenia and altered plasma levels of most of the proteins involved in haemostasis. Although liver disease was historically classified as a haemostasis-related bleeding disorder, it has now been well established that the antihaemostatic changes that promote bleeding are compensated for by prohaemostatic changes. Conventional coagulation tests however do not accurately reflect these prohaemostatic changes, resulting in an underestimation of haemostatic potential. Novel coagulation tests, such as viscoelastic tests (VETs) and thrombin generation assays (TGAs) better reflect the net result of the haemostatic changes in patients with liver disease, and demonstrate a new, "rebalanced" haemostatic status. Although rebalanced, this haemostatic status is more fragile than in patients without liver disease. Patients with liver disease are therefore not only at risk of bleeding but also at risk of thrombosis. Notably, however, many haemostatic complications in liver disease are not related to the haemostatic failure. It is, therefore, crucial to identify the cause of the bleed or thrombotic complication in order to provide adequate treatment. In this paper, we will elaborate on the haemostatic changes that occur in liver disease, reflect on laboratory and clinical studies over the last few years, and explore the pathophysiologies of bleeding and thrombosis in this specific patient group.

Acquired bleeding disorders

“…ADAMTS13, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13; PAI‐1, plasminogen activator inhibitor‐1; TAFI, thrombin activatable fibrinolysis inhibitor; tPA, Tissue plasminogen activator; VWF, von Willebrand factor. Modified from van den Boom and Lisman with permission 46 …”

Gerinnungsstörungen bei Leberzirrhose – Diagnostik und Management

“…Ebenso können virale Infektionen, eine Eisenüberladung und Medikamente (z. B. Azathioprin, Antibiotika, Interferon) myelotoxische Effekte aufweisen und eine Thrombozytopenie bei chronischen Lebererkrankungen aggravieren [12]. Neben der verminderten absoluten Anzahl der Thrombozyten sind diese zudem oftmals in ihrer Funktion verändert (Thrombozytopathie).…”

“…In Studien konnte gezeigt werden, dass VET-Parameter die Funktion des hämostatischen Systems bei Patienten mit (kompensierter) Zirrhose adäquat widerspiegeln können [11,12]. Während VET-Verfahren bereits routinemäßig in der herzchirurgischen Intensivmedizin sowie nicht selten bei traumatologischen Schockraumpatienten verwendet werden, können sie auch im Rahmen von Lebertransplantationen und anderen invasiven Eingriffen bei Zirrhosepatienten als zentrales Instrument zur Steuerung des Transfusionsmanagements sinnvoll eingesetzt werden und stellen eine vielversprechende Ergänzung für den klinischen Alltag dar [11,27].…”

Treatment of portal vein thrombosis in cirrhosis with anticoagulation—more than meets the eye?

“…The downside of anticoagulant therapy is an increased bleeding risk. Patients with cirrhosis may acquire major alterations in their hemostatic system, which may make them more susceptible to anticoagulation-related bleeding complications ( 16 ). The decision to initiate or continue anticoagulation should thus be carefully weighed against the bleeding risk.…”