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

肝素样效应、因子 VII/XIII 缺乏和纤维蛋白溶解与肝硬化急性静脉曲张出血再出血风险的关系

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作者：Madhumita Premkumar, Rohit Mehtani, Anand V Kulkarni, Ajay Kumar Duseja, Arka De, Sunil Taneja, Virendra Singh, Nipun Verma, Jasmina Ahluwalia, Kamal Kajal, Smita Divyaveer, Akash Roy, Akash Gandotra, Narender Kalson, Kushal Kekan, Harmanpreet Kaur, Harpreet Kaur

期刊：

Digestive Diseases and Sciences

影响因子：

2.500

时间：

2023

起止号：

2023 Feb;68(2):497-513.

doi：

10.1007/s10620-022-07656-9

研究方向：

信号转导

Aims

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

Background

Hyperfibrinolysis and coagulation dysfunction may occur in cirrhotic patients with acute variceal bleed (AVB) despite successful endotherapy. Aims: To prospectively study the association of endogenous heparinoids and coagulation dysfunction with variceal rebleeding and outcome in cirrhosis.

Conclusions

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

Methods

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).

Results

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