%0 Journal Article
%T Platelet Function Decreases with Increasing Severity of Liver Cirrhosis and Portal Hypertension-A Prospective Study.
%A Brusilovskaya K
%A Hofer BS
%A Simbrunner B
%A Eichelberger B
%A Lee S
%A Bauer DJM
%A Mandorfer M
%A Schwabl P
%A Panzer S
%A Reiberger T
%A Gremmel T
%J Thromb Haemost
%V 123
%N 12
%D 2023 Dec 30
%M 37517407
%F 6.681
%R 10.1055/s-0043-1771187
%X <B>BACKGROUND: </B> Cirrhotic patients display an increased risk for both bleeding and thrombosis. We investigated platelet activation across Child-Pugh stages (CPSs) and portal hypertension (PH) severity.<BR><B>METHODS: </B> A total of 110 cirrhotic patients were prospectively included. CPS and hepatic venous pressure gradient (HVPG) were determined. Platelet surface expression of P-selectin and activated glycoprotein (GP) IIb/IIIa were measured by flow cytometry before/after stimulation with protease-activated receptor (PAR)-1 (thrombin receptor activating peptide, TRAP) and PAR-4 (AYPGKF) agonists, epinephrine, and lipopolysaccharide (LPS).<BR><B>RESULTS: </B> Platelet count was similar across CPS but lower with increasing PH severity. Expression of P-selectin and activated GPIIb/IIIa in response to TRAP and AYPGKF was significantly reduced in platelets of CPS-B/C versus CPS-A patients (all p < 0.05). Platelet P-selectin expression upon epinephrine and LPS stimulation was reduced in CPS-C patients, while activated GPIIb/IIIa in response to these agonists was lower in CPS-B/C (all p < 0.05). Regarding PH severity, P-selectin and activated GPIIb/IIIa in response to AYPGKF were lower in HVPG ≥20 mmHg patients (both p < 0.001 vs. HVPG < 10 mmHg). Similarly, activated GPIIb/IIIa was lower in HVPG ≥20 mmHg patients after TRAP stimulation (p < 0.01 vs. HVPG < 10 mmHg). The lower platelet surface expression of P-selectin and activated GPIIb/IIIa upon stimulation of thrombin receptors (PAR-1/PAR-4) in CPS-B/C and HVPG ≥20 mmHg patients was paralleled by reduced antithrombin-III levels in those patients (all p < 0.05). Overall, PAR-1- and PAR-4-mediated platelet activation correlated with antithrombin-III levels (p < 0.001).<BR><B>CONCLUSIONS: </B> Platelet responsiveness decreases with increasing severity of liver cirrhosis and PH but is potentially counterbalanced by lower antithrombin-III levels.