BACKGROUND & AIMS Endogenous heparinoids or heparin-like effects (HLEs) can cause coagulation failure in patients with cirrhosis and sepsis. We performed a prospective study of the association between HLE and bleeding events, sepsis, and outcomes of patients with severe alcohol-associated hepatitis. METHODS Our final analysis comprised 78 patients with severe alcohol-associated hepatitis (44.3 ± 11.7 years; all male; discriminant function >32) who presented without sepsis at a single center in India from August 2015 through August 2016. Blood samples were collected at days 0, 3, and 7 after presentation and assessed by a global coagulation assay; by SONOCLOT (global and heparinase treated); and in assays for factor VIII, von Willebrand factor, protein C, and antithrombin. Patients were followed for sepsis, bleeding and outcome. The primary outcome was association of HLE with survival 28 days after presentation. RESULTS HLEs were observed in 32 patients (41%) at day 0, 27 patients (34.6%) at day 3, and 28 patients (35.9%) patients at day 7. Factors associated with mortality at day 0 were factor VIII activity >160% (hazard ratio [HR], 3.1; 95% CI, 1.4-9.5; P = .026), level of protein C <34% (HR, 0.7; 95% CI, 0.5-0.8; P = .037), antithrombin activity <28% (HR, 0.7; 95% CI, 0.3-1.1; P = .008) and international normalized ratio >2.6 (HR, 2.3; 95% CI, 1.8-9.7; P = .010). In multivariate analyses, only factor VIII activity (HR, 2.3; 95% CI, 1.6-7.8; P = .046), international normalized ratio (1.9; 95% CI, 1.2-4.3; P = .039), level of protein C (HR, 0.9; 95% CI, 0.7-1.1; P = .052) and model for end-stage liver disease score (HR, 3.2; 95% CI, 1.9-10.2; P = .042) were associated with mortality. Episodes of epistaxis, hemorrhoid bleeding, hemoperitoneum, and pulmonary hemorrhage occurred in 10.2%, 12.3%, 3.4%, and 4.5% of patients respectively. The presence of HLE at day 0 increased the risk of sepsis (HR, 2.5; 95% CI, 2.2-4.3; P = .002), bleeding (HR, 1.4; 95% CI, 1.2-5.3; P = .004) and death (HR, 1.2; 95% CI, 1.4-1.7; P = .044). CONCLUSIONS In a prospective study of patients with severe alcohol-associated hepatitis, we associated HLE with coagulation abnormalities, risk of sepsis, and mortality. Clinicaltrials.govNCT02307409.

中文翻译：

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与严重酒精相关性肝炎患者出血、败血症和死亡风险相关的肝素样作用。

背景和目的 内源性类肝素或肝素样作用 (HLE) 可导致肝硬化和脓毒症患者的凝血功能障碍。我们对 HLE 与严重酒精相关性肝炎患者的出血事件、败血症和结局之间的关系进行了前瞻性研究。方法 我们的最终分析包括 2015 年 8 月至 2016 年 8 月在印度单一中心就诊的 78 名严重酒精相关性肝炎患者（44.3 ± 11.7 岁；所有男性；判别功能>32），他们在印度的一个中心就诊。每天收集血样0、3 和 7 呈现后并通过整体凝血试验进行评估；通过 SONOCLOT（全局和肝素酶处理）；在因子 VIII、血管性血友病因子、蛋白 C 和抗凝血酶的测定中。对患者的败血症、出血和结果进行随访。主要结果是 HLE 与就诊后 28 天的生存率相关。结果 第 0 天 32 名患者 (41%)、第 3 天 27 名患者 (34.6%) 和第 7 天 28 名患者 (35.9%) 观察到 HLE。与第 0 天死亡率相关的因素是因子 VIII 活性 >160 %（风险比 [HR]，3.1；95% CI，1.4-9.5；P = .026），蛋白 C 水平 <34%（HR，0.7；95% CI，0.5-0.8；P = .037），抗凝血酶活性 <28% (HR, 0.7; 95% CI, 0.3-1.1; P = .008) 和国际标准化比率 >2.6 (HR, 2.3; 95% CI, 1.8-9.7; P = .010)。在多变量分析中，只有因子 VIII 活性（HR，2.3；95% CI，1.6-7.8；P = .046），国际标准化比率（1.9；95% CI，1.2-4.3；P = .039），蛋白质水平C（HR，0.9；95% CI，0.7-1.1；P = .052）和终末期肝病评分模型（HR，3.2；95% CI，1.9-10.2；P = . 042）与死亡率相关。分别有 10.2%、12.3%、3.4% 和 4.5% 的患者发生鼻衄、痔出血、腹腔积血和肺出血。第 0 天出现 HLE 会增加败血症（HR，2.5；95% CI，2.2-4.3；P = .002）、出血（HR，1.4；95% CI，1.2-5.3；P = .004）的风险和死亡（HR，1.2；95% CI，1.4-1.7；P = .044）。结论 在一项针对严重酒精相关性肝炎患者的前瞻性研究中，我们将 HLE 与凝血异常、败血症风险和死亡率相关联。Clinicaltrials.govNCT02307409。出血（HR，1.4；95% CI，1.2-5.3；P = .004）和死亡（HR，1.2；95% CI，1.4-1.7；P = .044）。结论 在一项针对严重酒精相关性肝炎患者的前瞻性研究中，我们将 HLE 与凝血异常、败血症风险和死亡率相关联。Clinicaltrials.govNCT02307409。出血（HR，1.4；95% CI，1.2-5.3；P = .004）和死亡（HR，1.2；95% CI，1.4-1.7；P = .044）。结论 在一项针对严重酒精相关性肝炎患者的前瞻性研究中，我们将 HLE 与凝血异常、败血症风险和死亡率相关联。Clinicaltrials.govNCT02307409。