How does liver disease affect the Activated Partial Thromboplastin Time (APTT)?

From the Guidelines

Liver disease can lead to a rebalanced hemostatic system, where the risks of bleeding and thrombosis are simultaneously increased due to changes in primary and secondary hemostasis and the fibrinolytic system 1.

Key Changes in Hemostasis

• Thrombocytopenia: common in patients with cirrhosis, with 80% of patients having platelet counts below the lower limit of normal 1
• Decreased coagulation factors: reduced plasma levels of coagulation factors, inhibitors of coagulation, and fibrinolytic factors 1
• Elevated von Willebrand factor (VWF): counteracts thrombocytopenia and supports platelet adhesion 1
• Altered fibrinolysis: increased by reduced alpha2-antiplasmin, FXIII, and thrombin activatable fibrinolysis inhibitor and elevated tissue plasminogen activator levels 1

Impact on Activated Partial Thromboplastin Time (APTT)

• Prolonged APTT: may occur due to reduced coagulation factors, but does not necessarily indicate a bleeding tendency 1
• Limited predictive value: traditional laboratory measures of coagulation, including APTT, have proven inadequate and often misleading in the evaluation of hemostasis in cirrhosis 1

Clinical Implications

• Caution in interpreting coagulation tests: results should be interpreted with caution, taking into account the complex changes in hemostasis and the limitations of traditional laboratory measures 1
• Individualized approach: management of patients with liver disease and coagulopathy should be individualized, considering the specific clinical context and the presence of other risk factors for bleeding or thrombosis 1

From the Research

Effect of Liver Disease on APTT

• Liver disease is accompanied by profound hemostatic disturbances, which can affect the Activated Partial Thromboplastin Time (APTT) 2.
• APTT is dependent on factors II, IX, and X levels, and its prolongation can be seen in patients with liver disease due to decreased synthesis of these factors 2.
• However, the relationship between APTT and bleeding risk in liver disease is complex, and APTT may not accurately reflect the risk of bleeding or thrombosis in patients with liver failure 3, 4, 5.
• In fact, studies have shown that patients with liver cirrhosis may exhibit a prothrombotic profile, despite having prolonged APTT and PT/INR, suggesting that these parameters may not be reliable for assessing bleeding risk 6.

Mechanisms Underlying APTT Changes in Liver Disease

• The liver plays a key role in hemostasis, synthesizing many proteins involved in coagulation, antithrombotic, and fibrinolytic systems 5.
• Liver disease can lead to decreased synthesis of procoagulant and anticoagulant factors, resulting in a rebalanced coagulation system 3.
• However, this rebalanced system may still be prone to thrombosis, and APTT may not accurately reflect this risk 6.

Clinical Implications

• The use of APTT and PT/INR to assess bleeding risk in liver disease has been questioned, and alternative biomarkers may be needed to accurately predict bleeding risk 6, 4.
• Further studies are needed to evaluate the relationship between APTT, PT/INR, and bleeding risk in liver disease, and to develop more accurate and reliable tests for assessing coagulation status in these patients 2, 4.