From the Guidelines
Cirrhotic patients are hypercoagulable due to an imbalance in the hemostatic system, despite traditional coagulation tests suggesting otherwise. This paradoxical hypercoagulability occurs because cirrhosis creates a complex interplay of procoagulant and anticoagulant factors. According to the most recent study 1, patients with cirrhosis have a laboratory hemostatic profile resembling disseminated intravascular coagulation (DIC), but with notable hypercoagulable features. The study highlights that the hemostatic balance in patients with cirrhosis is unstable and can alter over time, leading to both bleeding and thrombotic complications.
Key factors contributing to the hypercoagulable state in cirrhosis include:
- Decreased production of procoagulant factors (like factors II, V, VII, IX, X, XI) manufactured by the liver
- Reduced production of natural anticoagulants (protein C, protein S, and antithrombin)
- Elevated levels of factor VIII and von Willebrand factor, which promote clotting
- Increased thrombin generation and decreased fibrinolysis, further tipping the balance toward a prothrombotic state
- Thrombocytopenia, though common in cirrhosis, is often counterbalanced by the presence of larger, more adhesive platelets
- Portal hypertension and reduced blood flow in the portal system create conditions favorable for clot formation, particularly in the portal and splanchnic circulation.
As noted in a previous study 1, the coagulation cascade is rebalanced in patients with cirrhosis, resulting in a relative hypercoagulable state, as evidenced by the increased risk for both portal vein thrombosis (PVT) and venous thromboembolism (VTE). This highlights the importance of considering the hypercoagulable state in cirrhosis when assessing bleeding risk and making decisions about anticoagulation therapy.
From the Research
Coagulopathy in Cirrhosis
- Cirrhosis patients are at a risk of both bleeding and thrombosis, with hypercoagulability potentially promoting hepatic decompensation and development of fibrosis 2.
- The condition was previously considered a prototype acquired coagulopathy responsible for bleeding, but recent evidence suggests it should be regarded as a condition associated with normal or even increased thrombin generation 3.
Hypercoagulability in Cirrhosis
- Elevated levels of factor VIII and decreased protein C in patients with cirrhosis can lead to a procoagulant imbalance, defined as a partial resistance to the in vitro anticoagulant action of thrombomodulin 3.
- This imbalance may have clinical consequences, including an increased risk of venous thromboembolism or portal vein thrombosis, and potentially contributing to the progression of liver fibrosis 3, 4.
Pathophysiological Bases of Coagulation Abnormalities
- The liver plays a central role in the clotting process, synthesizing the majority of coagulation factors and proteins involved in fibrinolysis, as well as thrombopoietin, which is responsible for platelet production from megakaryocytes 5.
- Patients with liver disease have a disturbed balance of procoagulant and anti-coagulant factors, which deviates from the normal coagulation cascade, posing an additional problem in the diagnostic and therapeutic approach to this group of patients 5.
Primary Hemostasis in Patients with Cirrhosis
- Patients with cirrhosis develop complex alterations in primary hemostasis, including both hypocoagulable and hypercoagulable features, such as thrombocytopenia, multiple alterations of platelet function, and increased plasma levels of von Willebrand factor 6.
- A more comprehensive and individualized risk assessment should combine hemostatic impairment, the severity of decompensation and systemic inflammation, and the presence of additional factors that may impair platelet function 6.