The Spectrum of Disease Severity in Cirrhosis and Its Implications for Hemostasis

Abstract

Bleeding and thrombosis are both common complications that patients with advanced liver disease experience. While hemostatic pathways remain largely intact with cirrhosis, this balance can quickly shift in the direction of bleeding or clotting in an unpredictable manner. A growing body of literature is attempting to shed light on difficult scenarios that clinicians often face, ranging from predicting and mitigating bleeding risk in those who need invasive procedures to determining the best strategies to manage both bleeding and thrombotic complications when they occur. Studies examining hemostasis in those with advanced liver disease, however, often include heterogeneous cohorts with varied methodology. While these studies often select a cohort of all types and degrees of cirrhosis, emerging evidence suggests significant differences in underlying systemic inflammation and hemostatic abnormalities among specific phenotypes of liver disease, ranging from compensated cirrhosis to decompensated cirrhosis and acute-on-chronic liver failure. It is paramount that future studies account for these differing disease severities if we hope to address the many critical knowledge gaps in this field.

Vascular Liver Disorders, Portal Vein Thrombosis, and Procedural Bleeding in Patients With Liver Disease: 2020 Practice Guidance by the American Association for the Study of Liver Diseases

“…Patients with cirrhosis can present with a wide spectrum of diseases, from well‐compensated cirrhosis to chronic decompensation to acute decompensation with multiorgan failure. ( 40 ) Advanced liver disease is associated with thrombocytopenia attributable to portal hypertension and a prolonged INR as a result of an impaired synthesis of coagulation factors. Although these coagulation indices are historically used to assess bleeding risk, they are misleading in patients with cirrhosis.…”

Haemostatic alterations and management of haemostasis in patients with cirrhosis

“…Only recently have studies begun to address the haemostatic status in critically ill patients with cirrhosis (i.e., those with acutely decompensated cirrhosis [AD] and acuteon-chronic liver failure [ACLF]). 11 Fisher and coworkers provided initial evidence that the haemostatic balance in patients with AD and ACLF remains in equilibrium, despite progressive deterioration in routine haemostatic tests (platelets, INR) and levels of individual haemostatic proteins. 24 The same group subsequently confirmed and extended these findings.…”

“…We will specifically focus on recent breakthroughs and do not intend to give a complete overview of the field which is covered elsewhere. [8][9][10][11][12][13]…”

Liver status and outcomes in patients without previous known liver disease receiving anticoagulant therapy for venous thromboembolism

“…[ 28 – 31 ] These findings might be partly explained by a significant decrease on thrombomodulin-mediated inhibition of thrombin [ 32 ]. Nevertheless, the predisposition for bleeding in both acute and chronic liver diseases remains controversial, [ 33 ] and some experts suggested that the liver inflammation might be a potential predictor for bleeding [ 34 ]. In this context, the association between liver enzymes at VTE diagnosis and a higher risk for bleeding or to die might help to establish the basis for an association between the thrombosis–bleeding balance and the liver status in patients with undetected hepatic disease.…”