Imbalance of the coagulation-anticoagulation-fibrinolytic system: Pathogenesis and therapeutic approaches in progressive liver injury

Abstract

The coagulation-anticoagulation-fibrinolysis system is essential for normal hemostasis, and its key components are predominantly synthesized in the liver. During the progression of liver injury, reduced synthesis and increased consumption of coagulation factors occur concurrently, leading to an imbalance between coagulation and anticoagulation, and the establishment of an unstable rebalanced state. At the systemic level, these derangements tend to manifest as a relative hypocoagulable phenotype with elevated bleeding tendency. In contrast, the intrahepatic microcirculation, characterized by tissue factor exposure and sluggish portal perfusion, preferentially promotes local prothrombotic changes and accumulation of coagulation factors, particularly during advanced cirrhotic stages, resulting in a regionally hypercoagulable milieu despite systemic coagulation instability. Combined with the reduced synthesis of anticoagulant factors, these changes may create a prothrombotic, low-flow microenvironment within the intrahepatic and portal venous compartments, which is closely associated with intrahepatic microcirculatory disturbances and portal vein thrombosis. Given the bidirectional interplay between this dynamic imbalance and liver injury progression, a thorough understanding of the underlying regulatory mechanisms and the development of targeted interventions are paramount for mitigating liver injury. To gain deeper insights into the evolution of the coagulation-anticoagulation-fibrinolysis system in the context of advanced chronic liver disease/cirrhosis and portal microcirculatory or thrombotic complications, we searched MEDLINE, PubMed Central, and Bookshelf via PubMed to identify relevant literature on the coagulation-anticoagulation-fibrinolysis system and liver injury, and discuss corresponding therapeutic strategies.

Keywords: Coagulation-anticoagulation-fibrinolysis system; Liver injury; Rebalanced state; Intrahepatic microcirculatory disturbance; Portal vein thrombosis; Coagulopathy; Therapeutic strategies

Core Tip: During the progression of liver injury, an imbalance in the coagulation-anticoagulation-fibrinolysis cascade results in a complex hemostatic state: Systemic hypocoagulability with bleeding tendency vs intrahepatic and portal hypercoagulability with thrombotic risk. This dichotomy drives microcirculatory dysfunction, portal vein thrombosis, and disease aggravation. This review summarizes the dynamics of these changes, their pathological implications, and therapeutic interventions, offering a theoretical backing for the management of liver injury.