Abstract：
BACKGROUND: Dysregulated host response to infection causes life-threatening organ dysfunction. Excessive inflammation and abnormal blood coagulation can lead to disseminated intravascular coagulation (DIC) and multiple-organ failure in the late sepsis stages. Platelet function impairment in sepsis contributes to bleeding, secondary infection, and tissue injury. Platelet transfusion is considered in patients with sepsis with DIC and bleeding; however, its benefits are limited and of low quality. Fibrinogen plays a crucial role in platelet function, and establishing a fibrin network binds to activated integrin αIIbβ3 and promotes outside-in signaling that amplifies platelet functions. However, the role of fibrinogen in sepsis-induced platelet dysfunction remains unclear.
METHODS: We evaluated the effects of fibrinogen on platelet hyporeactivity during septic shock in adult male Wistar rats using lipopolysaccharide (LPS) injection and cecal ligation and puncture (CLP) surgery. Changes in the hemodynamic, biochemical, and coagulation parameters were examined. Platelet activation and aggregation were measured using whole-blood assay, 96-well plate-based aggregometry, and light-transmission aggregometry. Additionally, platelet adhesion, spreading, and fibrin clot retraction were evaluated.
RESULTS: Rats with LPS- and CLP-induced sepsis displayed considerable decreases in plasma fibrinogen levels and platelet aggregation, adhesion, spreading, and clot retraction. The aggregation of platelets obtained from rats with sepsis was markedly augmented by fibrinogen supplementation. Additionally, fibrinogen administration improved platelet adhesion, spreading, and clot retraction in rats with sepsis.
CONCLUSIONS: Fibrinogen supplementation could serve as a potential therapeutic intervention for alleviating platelet hyporeactivity in patients with sepsis and bleeding.
METHODS: We evaluated the effects of fibrinogen on platelet hyporeactivity during septic shock in adult male Wistar rats using lipopolysaccharide (LPS) injection and cecal ligation and puncture (CLP) surgery. Changes in the hemodynamic, biochemical, and coagulation parameters were examined. Platelet activation and aggregation were measured using whole-blood assay, 96-well plate-based aggregometry, and light-transmission aggregometry. Additionally, platelet adhesion, spreading, and fibrin clot retraction were evaluated.
RESULTS: Rats with LPS- and CLP-induced sepsis displayed considerable decreases in plasma fibrinogen levels and platelet aggregation, adhesion, spreading, and clot retraction. The aggregation of platelets obtained from rats with sepsis was markedly augmented by fibrinogen supplementation. Additionally, fibrinogen administration improved platelet adhesion, spreading, and clot retraction in rats with sepsis.
CONCLUSIONS: Fibrinogen supplementation could serve as a potential therapeutic intervention for alleviating platelet hyporeactivity in patients with sepsis and bleeding.
摘要：
背景：宿主对感染的反应失调会导致危及生命的器官功能障碍。在脓毒症晚期，过度的炎症和异常的凝血可导致弥散性血管内凝血（DIC）和多器官功能衰竭。败血症中血小板功能受损导致出血,继发感染,和组织损伤。有DIC和出血的脓毒症患者考虑血小板输注;然而,它的好处是有限的和低质量的。纤维蛋白原在血小板功能中起着至关重要的作用，和建立一个纤维蛋白网络与活化的整合素αIIbβ3结合，并促进外内信号传导，从而放大血小板功能。然而,纤维蛋白原在脓毒症诱导的血小板功能障碍中的作用尚不清楚.
方法：我们使用脂多糖（LPS）注射和盲肠结扎穿孔（CLP）手术评估了纤维蛋白原对成年雄性Wistar大鼠感染性休克期间血小板低反应性的影响。血液动力学的变化，生物化学，并检查凝血参数。使用全血测定法测量血小板活化和聚集，基于96孔板的聚集测定法，和光透射聚集测定法。此外,血小板粘附,传播,和纤维蛋白凝块回缩进行评估。
结果：LPS和CLP诱导的脓毒症大鼠血浆纤维蛋白原水平和血小板聚集显著下降，附着力,传播,和凝块收缩。补充纤维蛋白原可显着增强从脓毒症大鼠获得的血小板的聚集。此外,纤维蛋白原给药改善血小板粘附，传播,和脓毒症大鼠的血块收缩。
结论：补充纤维蛋白原可以作为减轻脓毒症和出血患者血小板低反应性的潜在治疗干预措施。
方法：我们使用脂多糖（LPS）注射和盲肠结扎穿孔（CLP）手术评估了纤维蛋白原对成年雄性Wistar大鼠感染性休克期间血小板低反应性的影响。血液动力学的变化，生物化学，并检查凝血参数。使用全血测定法测量血小板活化和聚集，基于96孔板的聚集测定法，和光透射聚集测定法。此外,血小板粘附,传播,和纤维蛋白凝块回缩进行评估。
结果：LPS和CLP诱导的脓毒症大鼠血浆纤维蛋白原水平和血小板聚集显著下降，附着力,传播,和凝块收缩。补充纤维蛋白原可显着增强从脓毒症大鼠获得的血小板的聚集。此外,纤维蛋白原给药改善血小板粘附，传播,和脓毒症大鼠的血块收缩。
结论：补充纤维蛋白原可以作为减轻脓毒症和出血患者血小板低反应性的潜在治疗干预措施。
