ROTEM-detected hypocoagulability is associated with major non-portal hypertensive bleeding in cirrhosis

Abstract

Background: Patients with acute-on-chronic liver failure (ACLF) display preserved thrombin generation (TG) but hypocoagulable profiles on rotational thromboelastometry (ROTEM). The relationship with non-portal hypertensive (NPH) bleeding is unclear. The primary aim was to assess hemostatic alterations across the clinical spectrum of cirrhosis, including stable cirrhosis (SC), stable decompensation (SD), acute decompensation (AD), and ACLF, and their association with NPH bleeding.

Methods: In this prospective cohort and nested case-control study, 215 cirrhotic patients (SC=70; SD=50; AD=53; ACLF=42) underwent coagulation testing, including conventional coagulation tests, coagulation factors and inhibitors, ROTEM and TG [±thrombomodulin (TM)].

Results: ACLF patients showed a higher prevalence of hypocoagulable ROTEM profiles (≥5 abnormal parameters) compared with SC, SD, and AD (23.8% vs. 0% in SC and 4% in SD, p<0.05; 13.2% in AD, p=0.33), while TG potential with TM was comparable across groups. Major NPH bleeding (spontaneous and post-procedural) occurred in 8.4% of patients, with a prevalence of 17% in AD and 21.4% in ACLF. Patients with NPH bleeding more frequently exhibited a hypocoagulable ROTEM profile compared with those without bleeding (44.4% vs. 5.1%, p<0.001). Using LASSO-penalized logistic regression, a hypocoagulable ROTEM profile showed the strongest independent association with NPH bleeding (λ₁se model: OR 1.48, 95% CI 1.17-2.06; cross-validated AUC 0.75). The λ_min model showed incrementally higher discriminative performance (cross-validated AUC 0.79) and additionally included MELD-Na score (confounder), bacterial infection, fibrinogen, and platelet count, but a hypocoagulable ROTEM profile also showed the strongest association (OR 2.02, 95% CI 1.30-3.15), comparable to the results in the more parsimonious λ₁se model.

Conclusions: ROTEM-detected hypocoagulability was independently associated with major NPH bleeding in cirrhosis. Its clinical implications warrant further investigation.

Keywords: acute-on-chronic liver failure; cirrhosis; coaguation; hemostasis; hypocoagulability; non-portal hypertensive bleeding; rotational thromboelastometry.