Whole blood thrombin generation shows a significant hypocoagulable state in patients with decompensated cirrhosis.

Autor: Zanetto A; Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padova University Hospital, Padova, Italy. Electronic address: https://twitter.com/azanetto., Campello E; General Internal Medicine Unit, Azienda Ospedale - Università Padova, Padova, Italy; Thrombotic and Haemorrhagic Disease Unit and Haemophilia Center, Department of Medicine, University of Padova, Italy., Bulato C; Thrombotic and Haemorrhagic Disease Unit and Haemophilia Center, Department of Medicine, University of Padova, Italy., Willems R; Department of Functional Coagulation, Synapse Research Institute, Maastricht, The Netherlands; Department of Internal Medicine, Section Vascular Medicine, Maastricht University Medical Center, Maastricht, The Netherlands; Cardiovascular Research Institute Maastricht, School for Cardiovascular Diseases, Maastricht, The Netherlands., Konings J; Department of Functional Coagulation, Synapse Research Institute, Maastricht, The Netherlands., Roest M; Department of Functional Coagulation, Synapse Research Institute, Maastricht, The Netherlands., Gavasso S; Thrombotic and Haemorrhagic Disease Unit and Haemophilia Center, Department of Medicine, University of Padova, Italy., Nuozzi G; Thrombotic and Haemorrhagic Disease Unit and Haemophilia Center, Department of Medicine, University of Padova, Italy., Toffanin S; Thrombotic and Haemorrhagic Disease Unit and Haemophilia Center, Department of Medicine, University of Padova, Italy., Zanaga P; Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padova University Hospital, Padova, Italy., Burra P; Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padova University Hospital, Padova, Italy., Russo FP; Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padova University Hospital, Padova, Italy., Senzolo M; Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padova University Hospital, Padova, Italy., de Laat B; Department of Functional Coagulation, Synapse Research Institute, Maastricht, The Netherlands., Simioni P; General Internal Medicine Unit, Azienda Ospedale - Università Padova, Padova, Italy; Thrombotic and Haemorrhagic Disease Unit and Haemophilia Center, Department of Medicine, University of Padova, Italy. Electronic address: paolo.simioni@unipd.it.
Jazyk: angličtina
Zdroj: Journal of thrombosis and haemostasis : JTH [J Thromb Haemost] 2024 Feb; Vol. 22 (2), pp. 480-492. Date of Electronic Publication: 2023 Oct 21.
DOI: 10.1016/j.jtha.2023.10.008
Abstrakt: Background: Patients with cirrhosis have a normal to increased thrombin generation (TG) capacity in platelet-poor plasma (PPP). By reflecting the contribution of all circulating blood cells, whole blood (WB) TG may allow a more physiological assessment of coagulation.
Objectives: We compared WB-TG vs PPP-TG in patients with cirrhosis.
Methods: Assessment of coagulation included routine tests, factor VIII, natural anticoagulants, PPP-TG, and WB-TG. TG assays were performed with and without thrombomodulin. Twenty-five healthy subjects were included as controls.
Results: We included 108 patients (Child-Pugh A/B/C, 44/24/40). Compared with controls, patients had significantly lower platelet count, longer international normalized ratio, higher FVIII, and lower levels of protein C/S and antithrombin. Regarding thrombomodulin-modified TG assays, in compensated cirrhosis, both PPP-TG and WB-TG indicated an increased TG capacity, as reflected by an endogenous thrombin potential (ETP) significantly higher than controls. In contrast, in decompensated cirrhosis, PPP-TG indicated a hypercoagulable state with increased ETP, higher peak height, and shorter time-to-peak than controls, whereas WB-TG revealed a progressive impairment of TG kinetics and total capacity, ultimately resulting in a profound hypocoagulable state in patients with Child-Pugh C cirrhosis (ie, significant prolongation of lag time and time-to-peak with reduction of both ETP and peak height). In decompensated patients, bacterial infections and severity of anemia were associated with a further reduction of both ETP and peak height.
Conclusion: Compensated cirrhosis is associated with an increased TG capacity. In decompensated cirrhosis, contrary to PPP-TG, which indicates hypercoagulability, WB-TG shows a significant hypocoagulable state. The clinical value of these findings deserves further investigation.
Competing Interests: Declaration of competing interests There are no competing interests to disclose.
(Copyright © 2023 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE