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

Alberto Zanetto; Elena Campello; Cristiana Bulato; Ruth Willems; Joke Konings; Mark Roest; Sabrina Gavasso; Giorgia Nuozzi; Serena Toffanin; Paola Zanaga; Patrizia Burra; Francesco Paolo Russo; Marco Senzolo; Bas de Laat; Paolo Simioni

doi:10.1016/j.jtha.2023.10.008

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

J Thromb Haemost. 2024 Feb;22(2):480-492. doi: 10.1016/j.jtha.2023.10.008. Epub 2023 Oct 21.

Authors

Affiliations

¹ Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padova University Hospital, Padova, Italy. Electronic address: https://twitter.com/azanetto.
² 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.
³ Thrombotic and Haemorrhagic Disease Unit and Haemophilia Center, Department of Medicine, University of Padova, Italy.
⁴ 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.
⁵ Department of Functional Coagulation, Synapse Research Institute, Maastricht, The Netherlands.
⁶ Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padova University Hospital, Padova, Italy.
⁷ 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.

PMID: 37866518
DOI: 10.1016/j.jtha.2023.10.008

Abstract

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.

Keywords: bleeding; coagulation; hemostasis; thrombosis.

MeSH terms

Anticoagulants
Blood Coagulation
Blood Coagulation Disorders* / complications
Blood Coagulation Tests
Humans
Liver Cirrhosis* / complications
Liver Cirrhosis* / diagnosis
Thrombin / metabolism
Thrombomodulin / metabolism
Thrombophilia*

Substances

Anticoagulants
Thrombin
Thrombomodulin