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

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