The concept of rebalanced hemostasis in patients with liver disease: Communication from the ISTH SSC working group on hemostatic management of patients with liver disease

Abstract

Patients with liver diseases acquire complex alterations in their hemostatic system that may lead to abnormalities in routine diagnostic test of hemostasis. Thrombocytopenia, prolongations in the prothrombin time and activated partial thromboplastin time, and decreased plasma fibrinogen are common in patients with advanced liver disease. Historically, liver diseases therefore have been classified as an acquired bleeding disorder. Laboratory and clinical observations have demonstrated that although routine diagnostic tests of hemostasis suggest a hypocoagulable state, patients with liver disease also tend to develop thrombotic events. Overall, patients have commensurate changes in both pro- and antihemostatic pathways. This new hemostatic balance, however, appears much more fragile than the hemostatic balance in individuals with normal liver function, and patients with liver disease can readily experience both hemostasis-related bleeding and thrombotic events. These insights into the hemostatic balance in patients with liver disease have led to revised recommendations for clinical management of hemostasis. In 2020, an SSC working group within the ISTH has been founded with the aim to disseminate new concepts on prevention and treatment of bleeding and thrombosis in patients with liver disease. The current document will outline the hemostatic changes in patients with liver disease, the limitations of routine diagnostic tests of hemostasis, and the concept of rebalanced hemostasis.

Keywords: bleeding; cirrhosis; liver diseases; thrombosis.

FIGURE 1

Hemostatic balance in patients with liver disease. Concomitant changes in both pro‐ and anti‐hemostatic pathways result in a ‘rebalanced’ hemostatic state in patients with liver disease. Panel A shows the hemostatic balance in healthy individuals, panel B shows the hemostatic balance in patients with liver disease together with the individual changes in the hemostatic system. The new hemostatic balance in patients with liver disease is much less stable compared to the balance in healthy individuals, as there is much less weight on each end of the hemostatic scale. Simultaneous changes promoting bleeding and promoting thrombosis occur in primary and secondary hemostasis, and fibrinolysis. Modified from Curr Opin Organ Transplant 2008; 13: 298–9 with permission from Wolters Kluwer Health. ADAMTS‐13, A Disintegrin And Metalloprotease with ThromboSpondin‐1 domain; APTT, activated partial thromboplastin time; FVIII, factor VIII; PT, prothrombin time; VWF, von Willebrand factor