Self Matthew, Coupland Lucy A, Aneman Anders
Intensive Care Unit, Liverpool Hospital, Liverpool, Australia.
Ingham Institute for Applied Medical Research, Liverpool, Australia.
Ann Intensive Care. 2025 Jul 31;15(1):110. doi: 10.1186/s13613-025-01528-x.
Acutely infected critically ill patients develop coagulopathies and perturbations to the fibrinolysis system that manifest as immunothrombosis. Whole blood viscoelastic testing, using an exogenous fibrinolytic agent to enhance fibrinolysis (FE-VET) can assess both processes of coagulation and fibrinolysis at the bedside. This scoping review aimed to illustrate clinical applicability, knowledge gaps and unmet needs for this emerging technology.
A systematic search of bibliographic databases and the grey literature was performed between the 10th October 2024 and the 14th January 2025 using a pre-published protocol and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guideline for scoping reviews (PRISMA-ScR). Studies reporting FE-VET to investigate fibrinolysis in acutely infected patients admitted to the intensive care unit were assessed, including associations with disease severity and clinical outcomes.
The search identified 297 studies with 24 included in this review. Fifteen studies were observational (12 prospective, 3 retrospective), 4 case reports and series, 2 validation studies, 2 letters, and 1 poster abstract. No randomised controlled trials were identified. Most studies used varying concentrations of tissue plasminogen activator (tPA) to enhance fibrinolysis, with FE-VET performed at a single time point and the lysis time to achieve 50% reduction of maximum clot firmness being the most frequently reported variable. Fibrinolysis resistance was the prevailing state reported in acute sepsis or COVID-19 infections and associated with increased disease severity and worse clinical outcomes.
Viscoelastic testing using a fibrinolysis enhancing agent demonstrated a spectrum of fibrinolysis resistance in acutely infected critically ill patients, associated with increased disease severity and mortality. Standardisation of the concentrations of fibrinolysis enhancing agents and the reporting of clot lysis parameters across testing devices are needed to establish reference values. This would improve future clinical studies of fibrinolysis, including trials of fibrinolytic therapies using a personalised medicine approach.
急性感染的危重症患者会出现凝血功能障碍和纤维蛋白溶解系统紊乱，表现为免疫性血栓形成。使用外源性纤维蛋白溶解剂增强纤维蛋白溶解的全血粘弹性检测（FE-VET）可在床边评估凝血和纤维蛋白溶解过程。本范围综述旨在阐明这项新兴技术的临床适用性、知识空白和未满足的需求。
于2024年10月10日至2025年1月14日期间，使用预先发表的方案对文献数据库和灰色文献进行系统检索，并根据系统评价和Meta分析的范围综述首选报告项目（PRISMA-ScR）进行报告。评估了报告FE-VET以研究入住重症监护病房的急性感染患者纤维蛋白溶解情况的研究，包括与疾病严重程度和临床结局的关联。
检索到297项研究，本综述纳入24项。15项研究为观察性研究（12项前瞻性研究，3项回顾性研究），4项病例报告及系列研究，2项验证性研究，2封信函和1篇海报摘要。未检索到随机对照试验。大多数研究使用不同浓度的组织纤溶酶原激活剂（tPA）来增强纤维蛋白溶解，FE-VET在单个时间点进行，达到最大血凝块硬度降低50%的溶解时间是最常报告的变量。纤维蛋白溶解抵抗是急性脓毒症或COVID-19感染中报告的主要状态，与疾病严重程度增加和临床结局较差相关。
使用纤维蛋白溶解增强剂的粘弹性检测在急性感染的危重症患者中显示出一系列纤维蛋白溶解抵抗情况，与疾病严重程度增加和死亡率相关。需要对纤维蛋白溶解增强剂的浓度进行标准化，并在不同检测设备间报告血凝块溶解参数，以建立参考值。这将改善未来纤维蛋白溶解的临床研究，包括使用个性化医疗方法的纤维蛋白溶解疗法试验。
