Decreased Platelet Aggregation in Patients with Decompensated Liver Cirrhosis and TIPS Implantation

Abstract

Transjugular intrahepatic portosystemic shunt (TIPS) implantation is an effective treatment of portal hypertension in patients with decompensated liver cirrhosis. However, some patients develop TIPS thrombosis with recurrence of portal hypertension. The role of platelets in TIPS thrombosis and the necessity of antiplatelet therapy is unclear. Therefore, we aimed to study platelet function in patients with liver cirrhosis prior to and after TIPS implantation. Platelet aggregation was tested in peripheral and portal-vein blood patient samples on the day (D) of TIPS implantation (D0), D4 and D30 following the procedure (platelet count above 100 × 103/µL, aspirin starting on D5) using whole-blood impedance aggregometry (WBIA) and light transmission aggregometry (LTA). In addition, surface platelet activation markers (P-selectin, activated GPIIb/IIIa) and platelet–neutrophil complexes (PNCs) were assessed by flow cytometry. Thrombin receptor activating peptide 6 (TRAP-6), adenosine diphosphate (ADP) and arachidonic acid (AA) were used as agonists. Healthy subjects were included as controls. Agonist-induced platelet aggregation was reduced (WBIA: TRAP-6 p < 0.01, ADP p < 0.01, AA p < 0.001; LTA: TRAP-6 p = 0.13, ADP p = 0.05, AA p < 0.01) in patients (D0, n = 13) compared with healthy subjects (n = 9). While surface activation markers at baseline were negligibly low, the percentage of PNCs was higher in patients than in controls (p < 0.05). ADP-induced P-selectin expression was increased (p < 0.001), whereas TRAP-6-induced GPIIb/IIIa activation was impaired (p < 0.001) in patients versus controls. PNC formation in response to agonists was not different between groups. Results did not differ between peripheral and portal-vein blood of patients (D0, n = 11) and did not change over time (D0, D4, D30) following TIPS implantation (n = 9). In summary, patients with decompensated liver cirrhosis display in vitro platelet aggregation defects in response to various agonists. Defective aggregation persists upon TIPS implantation. Therefore, we conclude that antiplatelet treatment to prevent TIPS thrombosis is questionable.

Gerinnungsstörungen bei Leberzirrhose – Diagnostik und Management

“…Während Patienten mit kompensierter bzw. stabiler Zirrhose unabhängig von der Thrombozytenzahl oftmals eine normale oder erhöhte Thrombozytenadhäsion und ‑aggregation aufweisen, was auf erhöhte zirkulierende Konzentrationen des vWF und eine verminderte ADAMTS13 (ADAM-Metallopeptidase mit Thrombospondin-Typ-1-Motiv 13)-Aktivität zurückgeführt wird 5 13 , weisen Patienten mit dekompensierter Leberzirrhose oftmals eine gestörte Thrombozytenaktivierung und verminderte Thrombozytenaggregation auf, wobei das Ausmaß der Thrombozytenfunktionsstörung mit dem Schweregrad der portalen Hypertension in Zusammenhang steht 14 15 16 . Diese pathologischen Veränderungen der Thrombozytenfunktion werden auf die vorherrschende systemische Inflammationsreaktion, defekte Signaltransduktionsmechanismen, eine gestörte Thromboxan-A2-Produktion und eine erhöhte Freisetzung aggregationshemmender Substanzen wie Prostazykline und Stickstoffmonoxid zurückgeführt 2 5 11 .…”