Modern aspects of anticoagulant therapy in patients with liver cirrhosis: pathophysiology, pharmacokinetics and clinical management

ABSTRACT. Historically, the use of anticoagulant therapy (ACT) in liver cirrhosis (LC) was limited by the concept of “autoanticoagulation”. Current data support the “rebalanced hemostasis” paradigm, which posits that patients with LC are in a latent prothrombotic state and exhibit an increased incidence of venous thromboembolic complications. The practical use of ACT remains associated with altered drug pharmacokinetics, bleeding risk, and a lack of large, randomized trials. The aim of this review is to examine the evidence base, pharmacokinetic characteristics, and safety profiles of the main classes of anticoagulants, and propose algorithms for personalized ACT administration based on Child–Pugh score stratification. This article analyzes the potential use of ACT according to the degree of liver dysfunction and specifies the indications for ACT in thrombotic complications of LC. Particular attention is paid to new data (CIRROXABAN study) that indicate the potential role of factor Xa inhibitors in reducing the incidence of decompensation and modulating fibrogenesis. The choice of anticoagulant should be based on rigorous stratification using the Child–Pugh score, an assessment of clinical benefits, and comprehensive management of portal hypertension.

For citation: Suvorova NA, Smirnova VV, Kokorin VA. Modern aspects of anticoagulant therapy in patients with liver cirrhosis: Pathophysiology, pharmacokinetics and clinical management. Therapy (Moscow). 2026;12(5S):67–74.
https://doi.org/10.18565/ therapy.2026.5-s5.67-74

INTRODUCTION

Anticoagulation in patients with cirrhosis has historically raised serious clinical concerns. For decades, the prevailing view in hepatology was that cirrhosis was characterized solely by deficiencies in coagulation factors and associated thrombocytopenia. Prolonged prothrombin time (PT) and an elevated international normalized ratio (INR) were mistakenly regarded as evidence of protection against thrombosis, resulting in the systematic withholding of anticoagulation even when it was indicated for potentially life-threatening conditions.

Clinical and epidemiologic evidence accumulated over the past decade has fundamentally reshaped our understanding of hemostasis in chronic liver disease [1, 2]. Patients with cirrhosis are not protected from thromboembolic complications; instead, the incidence of venous thromboembolism (VTE) is higher in these patients than in the general population [3]. Current evidence indicates that cirrhosis is characterized not by hypocoagulation but by a state of rebalanced hemostasis, in which reduced synthesis of both procoagulant and anticoagulant factors is counterbalanced by concomitant changes in platelet function, fibrinolysis, and endothelial function [4–7].

This conceptual shift has paved the way for a more rational approach to anticoagulation. However, altered pharmacokinetics and the associated clinical risks necessitate individualized patient management.

PATHOPHYSIOLOGY OF HEMOSTASIS IN CIRRHOSIS

Cirrhosis is characterized by proportionate reductions in coagulation factors II, V, VII, IX, X, XI, and XII, together with reduced levels of the natural anticoagulants – protein C, protein S, antithrombin, and tissue factor pathway inhibitor (Table 1) [8, 9]. Consequently, global hemostatic assays, including thrombin generation assays and the Thrombodynamics assay, demonstrate preserved or even enhanced fibrin clot formation in most patients with compensated or decompensated cirrhosis [4]. Conventional coagulation tests, such as PT and INR, assess only plasma coagulation and do not account for critically important compensatory mechanisms [9].

Factor VIII and von Willebrand factor (VWF) are key components of this hemostatic balance. Because these proteins are produced both within the liver and by extrahepatic endothelial cells, their levels are preserved in cirrhosis and may even increase as part of a compensatory response [10]. Elevated VWF levels in the setting of marked deficiency of its regulatory protease, ADAMTS13, lead to the formation of ultralarge VWF multimers [11]. These multimers maintain effective platelet adhesion even in the presence of marked thrombocytopenia [5, 10, 12].

Thus, thrombocytopenia in cirrhosis is rarely the sole cause of bleeding, because the functional activity of the remaining platelets is markedly enhanced [13]. Together, these mechanisms create an underlying prothrombotic state that may manifest clinically as venous thrombosis, including portal vein thrombosis (PVT), hepatic vein thrombosis, and lower-extremity deep vein thrombosis. The annual incidence of these events is 1–2% in compensated cirrhosis and increases to 10–15% in decompensated cirrhosis [15]. PVT is present in 14–25% of patients with decompensated cirrhosis, and its prevalence correlates with the severity of portal hypertension and the progression of liver failure [6].

The principal pathophysiologic mechanisms underlying PVT include endothelial dysfunction and hemodynamic abnormalities associated with reduced portal venous flow velocity [5, 15]. Mechanical endothelial injury and local and systemic inflammation related to bacterial translocation from the intestine promote hepatic stellate cell activation and the release of procoagulant microvesicles [15]. Hypercoagulability is not the primary driver of PVT; portal hypertension plays the central role [9, 11]. The strongest predictors include reduced portal venous flow velocity, a platelet count <75 × 10⁹/L, a history of variceal bleeding, and previous PVT [9].

PHARMACOKINETIC AND PHARMACODYNAMIC CONSIDERATIONS FOR ANTICOAGULANT USE IN CIRRHOSIS

Selecting an anticoagulant for a patient with cirrhosis is clinically challenging. Hepatic impairment may alter the pharmacokinetic and pharmacodynamic profiles of all available anticoagulants, and these changes must be considered when initiating and monitoring treatment.

The anticoagulant effect of warfarin, a vitamin K antagonist (VKA), is highly variable because the synthesis of vitamin K–dependent coagulation factors is already impaired in cirrhosis and may be further affected by drug interactions and dietary factors [6]. Furthermore, INR is not a reliable predictor of bleeding risk in patients with cirrhosis, which complicates INR-based monitoring of VKA therapy [16]. Several meta-analyses have shown that VKAs are effective in achieving complete PVT recanalization [17, 18]. Their main advantages include extensive clinical experience, low cost, and oral administration. The principal limitations are the lack of clearly defined therap...

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N.A. Suvorova, V.V. Smirnova, V.A. Kokorin