Zanetto Alberto, Campello Elena, Bulato Cristiana, Gavasso Sabrina, Saggiorato Graziella, Shalaby Sarah, Burra Patrizia, Angeli Paolo, Senzolo Marco, Simioni Paolo
Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, Padova, Italy.
General Internal Medicine and Thrombotic and Hemorrhagic Diseases Unit, Department of Medicine, Padova University Hospital, Padova, Italy.
JHEP Rep. 2022 Apr 20;4(7):100493. doi: 10.1016/j.jhepr.2022.100493. eCollection 2022 Jul.
BACKGROUND & AIMS: Bacterial infections in cirrhosis are associated with increased bleeding risk. To assess the factors responsible for bleeding tendency in patients with bacterial infections, we conducted a prospective study comparing all 3 aspects of hemostasis (platelets, coagulation, and fibrinolysis) in hospitalized patients with decompensated cirrhosis with . without bacterial infections.
Primary hemostasis assessment included whole blood platelet aggregation and von Willebrand factor (VWF). Coagulation assessment included procoagulant factors (fibrinogen, factor II, V, VII, VIII, IX, X, XI, XII, XIII), natural anticoagulants (protein C, protein S, antithrombin) and thrombomodulin-modified thrombin generation test. Fibrinolysis assessment included fibrinolytic factors (plasminogen, t-PA, PAI-1, α2-AP, TAFIa/ai) and plasmin-antiplasmin complex (PAP).
Eighty patients with decompensated cirrhosis were included (40 with and 40 without bacterial infections). Severity of cirrhosis and platelet count were comparable between groups. At baseline, patients with cirrhosis and bacterial infections had significantly lower whole blood platelet aggregation, without significant differences in VWF. Regarding coagulation, bacterial infections were associated with reduced procoagulant factors VII and XII, and a significant reduction of all natural anticoagulants. However, thrombomodulin-modified thrombin generation was comparable between the study groups. Finally, although mixed potentially hypo-fibrinolytic (lower plasminogen) and hyper-fibrinolytic (higher t-PA) changes were present in bacterial infections, a comparable level of PAP was detected in both groups. Upon resolution of infection (n = 29/40), platelet aggregation further deteriorated whereas coagulation and fibrinolysis factors returned to levels observed in patients without bacterial infections.
In hospitalized patients with decompensated cirrhosis, bacterial infections are associated with reduced whole blood platelet aggregation and a significant decrease of all natural anticoagulants, which may unbalance hemostasis and potentially increase the risk of both bleeding and thrombosis.
Bacterial infections are a common issue in hospitalized patients with decompensated cirrhosis ( patients hospitalized due to severe complications of advanced chronic liver disease). Patients with decompensated cirrhosis who acquire infections may be at increased risk of bleeding complications following invasive procedures (that is a procedure in which the body is penetrated or entered, for instance by a needle or a tube). As bleeding complications in decompensated cirrhosis are associated with a high risk of further decompensation and death, there is an urgent need to understand the factors responsible for such increased bleeding tendency. Herein, we investigated the alterations of hemostasis (that is the physiological process responsible for clot formation and stability) in patients with decompensated cirrhosis and bacterial infections. We found that development of bacterial infections in these patients is associated with alterations of hemostasis (particularly of platelets and clotting cascade) that may increase the risk of both bleeding and thrombotic complications.
肝硬化患者的细菌感染与出血风险增加有关。为评估细菌感染患者出血倾向的相关因素，我们进行了一项前瞻性研究，比较失代偿期肝硬化住院患者有无细菌感染时止血的三个方面（血小板、凝血和纤溶）。
初级止血评估包括全血血小板聚集和血管性血友病因子（VWF）。凝血评估包括促凝血因子（纤维蛋白原、因子II、V、VII、VIII、IX、X、XI、XII、XIII）、天然抗凝剂（蛋白C、蛋白S、抗凝血酶）和血栓调节蛋白修饰的凝血酶生成试验。纤溶评估包括纤溶因子（纤溶酶原、t-PA、PAI-1、α2-AP、TAFIa/ai）和纤溶酶 - 抗纤溶酶复合物（PAP）。
纳入80例失代偿期肝硬化患者（40例有细菌感染，40例无细菌感染）。两组间肝硬化严重程度和血小板计数相当。基线时，肝硬化合并细菌感染患者的全血血小板聚集显著降低，VWF无显著差异。关于凝血，细菌感染与促凝血因子VII和XII降低以及所有天然抗凝剂显著减少有关。然而，血栓调节蛋白修饰的凝血酶生成在研究组之间相当。最后，尽管细菌感染时存在潜在的混合性低纤溶（纤溶酶原降低）和高纤溶（t-PA升高）变化，但两组中PAP水平相当。感染消退后（n = 29/40），血小板聚集进一步恶化，而凝血和纤溶因子恢复到无细菌感染患者中观察到的水平。
在失代偿期肝硬化住院患者中，细菌感染与全血血小板聚集降低和所有天然抗凝剂显著减少有关，这可能会破坏止血平衡并潜在增加出血和血栓形成的风险。
细菌感染是失代偿期肝硬化住院患者（因晚期慢性肝病严重并发症住院的患者）中的常见问题。发生感染的失代偿期肝硬化患者在侵入性操作（即身体被穿透或进入的操作，例如通过针头或导管）后出血并发症的风险可能增加。由于失代偿期肝硬化的出血并发症与进一步失代偿和死亡的高风险相关，迫切需要了解导致这种出血倾向增加的因素。在此，我们研究了失代偿期肝硬化合并细菌感染患者的止血（即负责血栓形成和稳定性的生理过程）变化。我们发现这些患者中细菌感染的发生与止血变化（特别是血小板和凝血级联反应）有关，这可能增加出血和血栓形成并发症的风险。
