Increased platelet aggregation in patients with decompensated cirrhosis indicates higher risk of further decompensation and death.

Abstract

Studies on platelet aggregation in cirrhosis are controversial because interpretation of platelet function is challenged by thrombocytopenia. We conducted a prospective study to investigate whole blood platelet aggregation in cirrhosis and its association with liver-related outcomes. Platelet aggregation was assessed by whole blood aggregometry (Multiplate®). To overcome the influence of platelet count and compare cirrhosis with thrombocytopenia vs. controls with normal platelet count, we calculated a ratio between platelet aggregation and platelet count (PLT ratio). Then, we prospectively followed patients with cirrhosis and ascertained predictors of decompensation, transplantation, and death. Two-hundred and three patients with cirrhosis were prospectively recruited (77% decompensated). PLT ratio was significantly higher in cirrhosis than in those with chronic hepatitis and healthy individuals (0.44 vs. 0.25 and 0.26, respectively; p <0.0001). In cirrhosis, the ratio increased with disease severity (Child-Pugh class C>B>A) and was particularly elevated in decompensated patients with severe thrombocytopenia. Among decompensated patients, 65 had further decompensation, underwent transplantation, or died during a 6-month follow-up. On multivariate analysis, PLT ratio (odds ratio 1.87; 95% CI 1.23-2.84; p= 0.003) and MELD score (odds ratio 1.05; 95% CI 1.01-1.08; p= 0.01) were independently associated with outcome. The relative risk of events was 7.5-fold higher in patients with PLT ratio >0.75 vs. patients with PLT ratio <0.25 (95% CI 2.5-21.9; p= 0.003). The increased PLT ratio, its discriminative ability for composite outcome, and the prognostic value of PLT ratio >0.75 were confirmed in an independent cohort of hospitalized patients with decompensated cirrhosis (n= 41). Patients with cirrhosis, particularly when decompensated, exhibit significantly increased whole blood platelet aggregation. Decompensated patients with a PLT ratio >0.75 have a >80% probability of further decompensation, transplantation, or liver-related death within 6 months. In patients with cirrhosis, previous studies have suggested that platelets (i.e. circulating blood cells that help form clots to stop bleeding) are dysfunctional. In particular, these studies suggested that platelet aggregation (the process by which platelets adhere to each other to form clots) is reduced. Since platelet aggregation is important for clot formation, it has been hypothesized that alterations of platelet aggregation may be responsible for the increased risk of bleeding observed in patients with cirrhosis. Our study demonstrates: i) that platelet aggregation in patients with cirrhosis is higher than in healthy individuals; ii) that platelet aggregation in patients with decompensated cirrhosis (i.e. those who have already experienced some complications of cirrhosis) is particularly elevated and associated with risk of further complications and death.