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

Author:

Nassar Asala12,Huber Jan Patrick1,Stallmann Daniela2,Sharipova Diana2,Hamad Muataz Ali234,Schultheiss Michael15,Thimme Robert1,Duerschmied Daniel267,Scharf Rüdiger Eberhard689,Bettinger Dominik1ORCID,Krauel Krystin26ORCID

Affiliation:

1. Department of Medicine II, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, D-79106 Freiburg, Germany

2. Department of Cardiology and Angiology I, Heart Center, University of Freiburg, D-79106 Freiburg, Germany

3. Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, D-79104 Freiburg, Germany

4. Faculty of Biology, University of Freiburg, D-79104 Freiburg, Germany

5. Berta-Ottenstein-Program, Faculty of Medicine, University of Freiburg, D-79106 Freiburg, Germany

6. Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, D-68167 Mannheim, Germany

7. European Center for AngioScience (ECAS) and German Center for Cardiovascular Research (DZHK), Partner Site Heidelberg/Mannheim, D-68167 Mannheim, Germany

8. Program in Cellular and Molecular Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA

9. Division of Experimental and Clinical Hemostasis, Hemotherapy, and Transfusion Medicine, Blood and Hemophilia Comprehensive Care Center, Institute of Transplantation Diagnostics and Cell Therapy, Heinrich Heine University Medical Center, D-40225 Düsseldorf, Germany

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.

Funder

Rolf. M. Schwiete Foundation

Deutsche Forschungsgemeinschaft

DFG

German, Austrian and Swiss Society of Thrombosis and Hemostasis Research

Publisher

MDPI AG

Subject

General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)

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