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.

Background: Coagulation alterations may contribute to cirrhosis progression. We explored whether increased thrombomodulin-modified thrombin generation (TM-TG) was associated with first hepatic decompensation in compensated cirrhosis. Methods: We retrospectively analyzed a prospectively collected cohort of 171 patients with compensated cirrhosis. TM-TG was measured at enrolment. The primary endpoint was the first hepatic decompensation. Time-to-event analyses were performed using cause-specific Cox models, with Fine–Gray models as a complementary competing risk approach. Results: Median age was 66 years, 66.7% were male, and 90.1% were Child–Pugh A; 70 (40.9%) patients had large varices. During a median follow-up of 3.3 years, 37 patients (21.6%) developed first hepatic decompensation. The 1-year, 2-year, 3-year, and 5-year cumulative incidences were 4.7%, 11.5%, 17.8%, and 31.5%, respectively. Compared with patients who remained compensated, those who developed first hepatic decompensation had lower platelet count (56 vs. 111 × 10 ⁹ /L), higher MELD score (9.97 vs. 8.93), more frequent large varices (73% vs. 36%), higher ETP-TM (822 vs. 752 nM min), and more often an ETP ratio >0.80 (70.3% vs. 44.0%) (all p <0.05). In multivariable analyses, higher ETP-TM remained independently associated with first hepatic decompensation in models including MELD (HR 1.27; sHR 1.30), large varices (HR 1.24; sHR 1.30), and platelet count (HR 1.29; sHR 1.31) (all p 0.80 was independently associated with first hepatic decompensation in models including MELD (HR 2.81; sHR 2.9), large varices (HR 2.96; sHR 2.7), and platelet count (HR 3.41; sHR 3.32) (all p <0.05). Conclusion: In compensated cirrhosis, increased TM-TG is associated with the first hepatic decompensation, although confirmation in prospective studies is warranted.