Surgical Research Laboratory, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, the Netherlands.
J Thromb Haemost. 2023 Oct;21(10):2747-2758. doi: 10.1016/j.jtha.2023.06.011. Epub 2023 Jun 17.
Previous studies identified decreased clot permeability, without differences in fibrin fiber density in clots, from patients with cirrhosis compared with those from healthy controls (HCs). Fibrinogen hypersialylation could be the reason for this discrepancy.
The aim of this work was to study mechanical properties of clots and reassess clot permeability in relation to hypersialylation in patients with stable cirrhosis, acute decompensation, and acute-on-chronic liver failure (ACLF). Sepsis patients without liver disease were included to distinguish between liver-specific and inflammation-driven phenotypes.
Pooled plasma was used for rheology and permeability experiments. Permeability was assessed with compression using a rheometer and by liquid permeation. Purified fibrinogen treated with neuraminidase was used to study the effects of fibrinogen hypersialylation on liquid permeation.
Mechanical properties of clots from patients with stable cirrhosis and acute decompensation were similar to those of clots from HCs, but clots from patients with ACLF were softer and ruptured at lower shear stress. Clots from sepsis patients without liver disease were stiffer than those from the other groups, but this effect disappeared after adjusting for increased plasma fibrinogen concentrations. Permeability was similar between clots under compression from HCs and clots under compression from patients but decreased with increasing disease severity in liquid permeation. Removal of fibrinogen sialic acid residues increased permeability more in patients than in controls.
Clots from patients with ACLF have weak mechanical properties despite unaltered fibrin fiber density. Previous liquid permeation experiments may have erroneously concluded that clots from patients with ACLF are prothrombotic as fibrinogen hypersialylation leads to underestimation of clot permeability in this setting, presumably due to enhanced water retention.
先前的研究表明，与健康对照组（HCs）相比，肝硬化患者的血栓通透性降低，而纤维蛋白纤维密度无差异。纤维蛋白原高唾液酸化可能是造成这种差异的原因。
本研究旨在研究稳定型肝硬化、急性失代偿和慢加急性肝衰竭（ACLF）患者血栓的机械性能，并重新评估与高唾液酸化相关的血栓通透性。纳入无肝病的脓毒症患者，以区分肝脏特异性和炎症驱动表型。
使用混合血浆进行流变学和通透性实验。使用流变仪通过压缩和液体渗透评估通透性。使用神经氨酸酶处理纯化的纤维蛋白原研究纤维蛋白原高唾液酸化对液体渗透的影响。
稳定型肝硬化和急性失代偿患者的血栓机械性能与 HCs 的血栓相似，但 ACLF 患者的血栓较软，在较低的剪切应力下破裂。无肝病的脓毒症患者的血栓比其他组的血栓更硬，但在调整增加的血浆纤维蛋白原浓度后，这种影响消失。HCs 压缩下的血栓和患者压缩下的血栓的渗透性相似，但随着疾病严重程度的增加，液体渗透的渗透性降低。去除纤维蛋白原唾液酸残基可增加患者的通透性，而对照组的通透性增加则较少。
尽管纤维蛋白纤维密度未改变，但 ACLF 患者的血栓机械性能较弱。先前的液体渗透实验可能错误地得出结论，认为 ACLF 患者的血栓具有促血栓形成性，因为在这种情况下，纤维蛋白原高唾液酸化导致对血栓通透性的低估，可能是由于水潴留增加所致。
