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

Table 1 Changes in factors in the coagulation-anticoagulation-fibrinolysis system in liver disease

Factors	Factors contributing to bleeding	Factors contributing to coagulation
Coagulation factors	Reduced procoagulant factors	Reduced anticoagulant factors. Increased factor VIII
Anticoagulant factors	Increased tissue factor pathway inhibitor	Reduced heparin cofactor II. Reduced antithrombin. Reduced protein C. Reduced thrombomodulin
Fibrinolytic pathway	Increased t-PA. Reduced TAFI. Reduced antiplasmin	Increased PAI-1 (more than t-PA). Reduced plasminogen
Platelets	Platelet dysfunction. Thrombocytopenia	Increased vWF. Reduced ADAMTS13

t-PA: Tissue plasminogen activator; PAI-1: Plasminogen activator inhibitor-1; TAFI: Thrombin-activatable fibrinolysis inhibitor; vWF: Von Willebrand Factor; ADAMTS13: A disintegrin and metalloproteinase with thrombospondin type 1 motif 13.

Table 2 Summary of blood products and/or pharmacological recommendations for thrombosis in cirrhosis

	Choice of agent	Statement	Limitations
Anticoagulation agents	LMWH	Monitor anti-FXa activity; evaluate anticoagulation efficacy	Short half-life; subcutaneous injection
	Warfarin	Inhibits vitamin K-dependent coagulation factor synthesis	Monitor INR to guide anticoagulation therapy; high bleeding risk
	Rivaroxaban	Inhibits FXa	Contraindicated or not recommended in severe hepatic impairment (Child-Pugh class C)
Antiplatelet agents	Aspirin or aspirin-magnesium-aluminum	Inhibits COX-1; blocks thromboxane A₂ formation. Suppresses platelet aggregation	Irritation of the gastrointestinal mucosa
	Clopidogrel or ticagrelor	Irreversibly inhibits the P2Y12 receptor on platelets and exerts antithrombotic activity	Risk of bleeding events

LMWH: Low-molecular-weight heparin; FXa: Activated factor X; INR: International normalized ratio; COX-1: Cyclooxygenase-1; P2Y12: Purinergic receptor Y12.