Impaired whole blood thrombin generation is associated with procedure-related bleeding in acutely decompensated cirrhosis

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

doi:10.1016/j.jhep.2024.12.008

Impaired whole blood thrombin generation is associated with procedure-related bleeding in acutely decompensated cirrhosis

J Hepatol. 2024 Dec 11:S0168-8278(24)02762-4. doi: 10.1016/j.jhep.2024.12.008. Online ahead of print.

Authors

Affiliations

¹ Department of Surgery, Oncology and Gastroenterology, University of Padova, Italy; Gastroenterology and Multivisceral Transplant Unit, Padova University Hospital, Padova, Italy.
² Department of Medicine (DIMED), University of Padova, Italy; First Chair of Internal Medicine and Thrombotic and Haemorrhagic Disease Unit, Padova University Hospital, Padova, Italy.
³ Department of Medicine (DIMED), 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; CARIM, School for Cardiovascular Diseases, Maastricht, the Netherlands.
⁵ Department of Functional Coagulation, Synapse Research Institute, Maastricht, The Netherlands.
⁶ Gastroenterology and Multivisceral Transplant Unit, Padova University Hospital, Padova, Italy.
⁷ Department of Medicine (DIMED), University of Padova, Italy; First Chair of Internal Medicine and Thrombotic and Haemorrhagic Disease Unit, Padova University Hospital, Padova, Italy. Electronic address: [email protected].

PMID: 39672204
DOI: 10.1016/j.jhep.2024.12.008

Abstract

Background & aims: The clinical utility of thrombomodulin-modified thrombin generation (TM-TG) in cirrhosis is uncertain. We conducted a prospective study to evaluate the prognostic value of TM-TG in cirrhosis.

Methods: Patients were recruited during outpatient clinics (compensated and stable decompensated) or if admitted to our inpatient service (acutely decompensated, AD). We performed whole blood (WB) and platelet-poor plasma (PPP) TM-TG at recruitment. All patients were prospectively followed-up for bleeding/thrombosis, hepatic decompensation, and liver-related death.

Results: We included 231 patients: 80 compensated, 70 stable decompensated, and 81 AD. Median follow-up was 414 days (range: 77-668). Eleven patients, all AD, experienced procedure-related bleeding. Both WB-TG and PPP-TG were more altered in bleeding vs. non-bleeding individuals (lower endogenous thrombin potential [ETP] and peak-height). However, only WB-TG could identify - at individual-patient level - those experiencing major bleeding (all having pre-procedural ETP <350 nmol/L*min). In AD, the area under the ROC curve of WB-TG ETP for bleeding was 0.854 (95%CI: 0.732-0.976), which was higher than that of PPP-TG ETP (0.676; 95%CI: 0.524-0.809). Neither WB-TG nor PPP-TG could predict development of thrombosis, mostly PVT (n=15). In compensated cirrhosis, WB-TG and PPP-TG were comparable between patients who experienced decompensation and those who did not. In decompensated cirrhosis, WB-TG and PPP-TG were more significantly altered in patients experiencing further decompensation/ACLF/liver-related death. A higher WB-TG ETP was linked to a lower risk of progression independently of MELD, Child-Pugh, and C-reactive protein (HR: 0.4, 95%CI: 95%: 0.21-0.79; p<0.01).

Conclusions: In compensated cirrhosis, WB-TG and PPP-TG do not improve risk stratification. In decompensated cirrhosis, WB-TG may be a promising tool for estimating procedure-related bleeding risk.

Trial registration number: NA.

Keywords: bleeding; coagulation; hemostasis; liver; thrombosis.