Association of Heparin-Like Effect, Factor VII/XIII Deficiency and Fibrinolysis with Rebleeding Risk in Cirrhosis with Acute Variceal Bleeding

Hyperfibrinolysis and coagulation dysfunction may occur in cirrhotic patients with acute variceal bleed (AVB) despite successful endotherapy.

To prospectively study the association of endogenous heparinoids and coagulation dysfunction with variceal rebleeding and outcome in cirrhosis.

Consecutive patients were assessed with conventional coagulation tests, SONOCLOT™ [(global(gb) and heparinase(h) treated] and factors VII, VIII, XIII, X, tissue plasminogen activator, and plasminogen activator inhibitor ELISA assays in a university hospital. Heparin-like-effect (HLE) was defined as ≥ 20% difference in paired gb/h-SONOCLOT™ traces for activated clotting time (ACT).

Of 143 patients screened, 90 (46.4 ± 11.7 years, males 82.2%, ethanol-related 58.8%) were recruited, who bled from esophageal varices (81,90.0%), gastric varices (6,6.6%), or esophageal varices with portal hypertensive gastropathy (3,3.3%). Twenty (21.7%) had early rebleeding, mainly post-variceal ligation ulcer related (70%). Patients who rebled had low Factor XIII [1.6 (1.2–2.1) vs 2.4 ng/ml (2.0–2.8) P = 0.035] and Factor VII (94.1 ± 46.9 vs. 124.0 ± 50.4, P = 0.023). On receiver operating curve analysis, the gbACT > 252 s (sensitivity 86.8%, specificity 76.9%, P < 0.001), hACT > 215 s (sensitivity 71.1%, specificity 70.3%, P < 0.001), and HLE > 50% (sensitivity 69.5%, specificity 70.3%, P = 0.006) predicted rebleeding. Baseline Factor VIII (HR 1.26; 95% CI 1.17–1.34, P < 0.001), low factor VII (HR 0.89; 95% CI 0.76–0.98, P = 0.035), and lysis (HR 1.25, 95% CI 1.17–1.33, P < 0.001) predicted mortality. Endogenous heparinoids at baseline predicted sepsis (HR 1.8; 95% CI 1.4–6.5; P = 0.022), rebleeding events (HR 1.2; 95% CI 1.1–6.3; P = 0.030), and mortality (HR 1.1; 95% CI 1.0–4.6; P = 0.030).

Hyperfibrinolysis, Factor VII/XIII deficiency, and HLE are associated with rebleeding after AVB.

Trial Registration NCT04111120 available from https://​clinicaltrials.​gov/​ct2/​show/​NCT04111120.