Undas Anetta
Department of Thromboembolic Diseases, Institute of Cardiology, Jagiellonian University Medical College, and Center for Research and Medical Technology, St. John Paul II Hospital, Cracow, Poland.
Semin Thromb Hemost. 2025 Sep;51(6):651-659. doi: 10.1055/s-0044-1787725. Epub 2024 Jun 18.
Congenital and acquired fibrinogen disorders often have heterogeneous clinical phenotypes and are challenging from a laboratory perspective. Fibrinogen determination using the Clauss method remains the gold standard, while the reproducibility and significance of the thrombin time and the reptilase time are limited. Molecular testing for causative mutations in fibrinogen genes is now recommended to confirm the diagnosis of congenital fibrinogen disorders. Research assays are used to evaluate alterations to fibrin formation and properties of plasma and purified fibrinogen-derived clots, characterized by fiber thickness, the number of branches, and pore sizes. Fibrin clot permeability (permeation, porosity) using a hydrostatic pressure system represents the most commonly used method for evaluating fibrin network density. Reduced clot permeability, which denotes the reduced size of an average pore in the network, results in tighter fibrin networks, typically associated with impaired susceptibility to lysis, leading to a thrombotic tendency. Biophysical properties of fibrin clots are largely assessed using rheometry, with atomic force microscopy and nanorheology being increasingly used in disease states. Thromboelastography and thromboelastometry, a simple modification of rheometry, have been used, mainly in intensive care units, for more than 50 years. Given growing evidence for altered fibrin clot properties in diseases with elevated risk of venous and arterial thromboembolism and in some bleeding disorders, further work on standardization and validation of the assessment of fibrin clot characteristics is needed. This review summarizes the current methods used to evaluate fibrinogen abnormalities in both diagnostic and research laboratories.
先天性和获得性纤维蛋白原异常通常具有异质性临床表型，从实验室角度来看具有挑战性。使用克劳斯法测定纤维蛋白原仍然是金标准，而凝血酶时间和爬虫酶时间的可重复性及意义有限。现在建议对纤维蛋白原基因的致病突变进行分子检测，以确诊先天性纤维蛋白原异常。研究检测用于评估纤维蛋白形成的改变以及血浆和纯化的纤维蛋白原衍生凝块的特性，其特征在于纤维厚度、分支数量和孔径大小。使用静水压力系统测定纤维蛋白凝块通透性（渗透、孔隙率）是评估纤维蛋白网络密度最常用的方法。凝块通透性降低表示网络中平均孔隙尺寸减小，会导致纤维蛋白网络更紧密，通常与纤溶易感性受损相关，进而导致血栓形成倾向。纤维蛋白凝块的生物物理特性主要使用流变学进行评估，原子力显微镜和纳米流变学在疾病状态下的应用越来越多。血栓弹力图和血栓弹力测定法是流变学的一种简单改良方法，主要在重症监护病房使用了50多年。鉴于越来越多的证据表明，在静脉和动脉血栓栓塞风险升高的疾病以及一些出血性疾病中，纤维蛋白凝块特性发生改变，因此需要进一步开展工作，对纤维蛋白凝块特征评估进行标准化和验证。本综述总结了诊断和研究实验室中用于评估纤维蛋白原异常的当前方法。
