Influence of Hepatocellular Carcinoma on Platelet Aggregation in Cirrhosis

Simple Summary Platelets are blood cells, the main function of which is to form clots and prevent/stop bleeding. However, it has been shown that platelets may be involved in additional pathophysiological processes, including stimulation of cancer growth and metastasis. In fact, inhibition of platelets in patients with various types of cancer has resulted in lower risks of cancer progression and death. This possibility has not yet been considered in patients with cirrhosis (chronic liver disease) and hepatocellular carcinoma (the most common type of liver cancer) because their platelet function has never been investigated. In this study, we show that hepatocellular carcinoma in patients with cirrhosis is associated with significantly altered (increased) platelet function. This paves the way for further studies to evaluate whether the inhibition of these hyper-functional platelets could be beneficial in patients with cirrhosis and hepatocellular carcinoma. Hyper-functional platelets are being proposed as a potential therapeutic target in multiple cancers. Whether this can be considered in patients with cirrhosis and hepatocellular carcinoma (HCC) is unknown as their platelet function has not yet been investigated. We evaluated platelet function in cirrhosis patients with HCC. Patients with cirrhosis with and without HCC were prospectively recruited. Platelet aggregation, a marker of platelet function, was assessed by impedance aggregometry with adenosine diphosphate (ADP), arachidonic acid (ASPI), and thrombin (TRAP) stimulation. Plasmatic levels of Von Willebrand factor antigen (VWF) were also determined. One-hundred patients were recruited (50 cirrhotics with and 50 without HCC). Cirrhosis severity by Child class and platelet count were comparable between cirrhotics with and without HCC. Cirrhotics with HCC had higher ADP- (45 vs. 28; p < 0.001), ASPI- (47 vs. 28; p < 0.001), and TRAP- (85 vs. 75; p = 0.01) induced platelet aggregation than cirrhotics without HCC, all indicative of platelet hyper-function. The relatively increased platelet aggregation in patients with HCC was confirmed after adjusting the analysis for platelet count/severity of thrombocytopenia. Levels of VWF were higher in patients with vs. without HCC (348 vs. 267; p = 0.006), particularly in compensated cirrhosis. In patients with cirrhosis, HCC is associated with increased platelet aggregation and higher VWF. The clinical implications of these findings deserve further investigation.

Automated summary

The study reveals a significant association between altered platelet function and hepatocellular carcinoma in patients with cirrhosis, suggesting the potential benefit of inhibiting hyper-functional platelets. The differences in platelet function may have important clinical implications for treatment.