Lisman Ton, Arefaine Bethlehem, Adelmeijer Jelle, Zamalloa Ane, Corcoran Eleanor, Smith John G, Bernal William, Patel Vishal C
Surgical Research Laboratory and Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Institute of Hepatology London, Foundation for Liver Research, London, UK.
J Thromb Haemost. 2021 Jan;19(1):85-95. doi: 10.1111/jth.15112. Epub 2020 Nov 29.
Essentials Liver diseases are associated with profound hemostatic changes proportional to severity of illness. Hemostatic changes in acute-on-chronic liver failure (ACLF) may in part reflect critical illness. Hemostatic changes in ACLF partly overlap with those in sepsis, with rebalanced hemostasis in both. Patients with sepsis had hyperfibrinogenemia, associated with a thrombogenic clot structure. ABSTRACT: Background Even the sickest patients with chronic liver disease (CLD), such as those with acute-on-chronic liver failure (ACLF) remain in hemostatic balance due to a concomitant decline in pro- and antihemostatic factors. Objectives We aimed to study whether the hemostatic status in ACLF is merely an exaggeration from the status in patients with compensated and acutely decompensated cirrhosis, or whether sepsis-associated hemostatic changes contribute. Methods We performed extensive hemostatic profiling in 31 adult patients with ACLF, 20 patients with sepsis without underlying CLD, and 40 healthy controls. Results We found similarly elevated plasma levels of the platelet adhesive protein von Willebrand factor (VWF) and decreased levels of the VWF-regulating protease ADAMTS13 in both groups compared to healthy controls. In vivo markers of activation of coagulation (thrombin-antithrombin III, D-dimer) were similarly elevated in both groups compared to controls, but ex vivo thrombin-generating capacity was similar between patients and controls, despite a much more profound international normalized ratio elevation in ACLF. Plasma fibrinogen levels were much higher in septics, which was accompanied by a decreased ex vivo clot permeability and an increase in ex vivo resistance to clot lysis. All hemostatic parameters were remarkably stable over the first 10 days after admission. Conclusions We have found hemostatic changes in ACLF to partially overlap with that of patients with sepsis, and evidence of preserved hemostatic capacity in both patient groups. The notable difference was a profound hyperfibrinogenemia, associated with a thrombogenic clot structure and a marked ex vivo resistance to fibrinolysis in patients with sepsis.
要点 肝脏疾病与严重的止血变化相关，且与疾病严重程度成正比。急性慢性肝衰竭（ACLF）中的止血变化可能部分反映了危重病况。ACLF中的止血变化部分与脓毒症中的变化重叠，两者的止血均重新平衡。脓毒症患者有高纤维蛋白原血症，与血栓形成性凝块结构相关。摘要：背景 即使是患有慢性肝病（CLD）的最病重患者，如急性慢性肝衰竭（ACLF）患者，由于促凝血和抗凝血因子同时下降，仍保持止血平衡。目的 我们旨在研究ACLF中的止血状态是否仅仅是代偿期和急性失代偿期肝硬化患者状态的加剧，或者脓毒症相关的止血变化是否起作用。方法 我们对31例成年ACLF患者、20例无基础CLD的脓毒症患者和40例健康对照进行了广泛的止血分析。结果 我们发现，与健康对照相比，两组患者血浆中血小板粘附蛋白血管性血友病因子（VWF）水平均同样升高，而调节VWF的蛋白酶ADAMTS13水平均下降。与对照相比，两组患者体内凝血激活标志物（凝血酶 - 抗凝血酶III、D - 二聚体）同样升高，但尽管ACLF患者的国际标准化比值升高更为显著，但患者和对照之间的体外凝血酶生成能力相似。脓毒症患者的血浆纤维蛋白原水平高得多，同时伴随着体外凝块通透性降低和体外对凝块溶解的抵抗力增加。入院后的前10天内，所有止血参数都非常稳定。结论 我们发现ACLF中的止血变化部分与脓毒症患者的变化重叠，且两组患者均有止血能力保留的证据。显著差异在于脓毒症患者有严重的高纤维蛋白原血症，与血栓形成性凝块结构相关，且体外对纤维蛋白溶解有明显抵抗力。
