Gyldenholm Tua, Hvas Anne-Mette, Christensen Thomas Decker, Larsen Julie Brogaard
Department of Clinical Biochemistry, Thrombosis and Haemostasis Research Unit, Aarhus University Hospital, Aarhus, Denmark.
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Semin Thromb Hemost. 2024 Apr;50(3):384-401. doi: 10.1055/s-0043-1775856. Epub 2023 Oct 9.
Venous thromboembolism (VTE) is a main contributor to morbidity and mortality in cancer patients. Biomarkers with the potential to predict cancer-associated VTE are continually sought. Of these, markers of thrombin generation present a likely option. The present systematic review examines the ability of three widely used biomarkers of thrombin generation: prothrombin fragment 1.2 (F1.2), thrombin-antithrombin complex (TAT), and ex vivo thrombin generation, to predict VTE in both solid and hematologic adult cancer patients. Relevant studies were identified in the PubMed and Embase databases, and the review conformed to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Each study was evaluated using the quality assessment tool from the National Heart, Lung, and Blood Institute. The review protocol was published on PROSPERO with identifier CRD42022362339. In total, 24 papers were included in the review: 11 reporting data on F1.2, 9 on TAT, and 12 on ex vivo thrombin generation. The quality ratings of the included studies varied from good ( = 13), fair ( = 8), to poor ( = 3) with a high heterogenicity. However, F1.2, TAT complex, and ex vivo thrombin generation were all found to be associated with the development of VTE. This association was most pronounced for F1.2. Furthermore, the determination of F1.2 was able to improve the precision of several established risk assessment scores. In conclusion, markers of thrombin generation were found to be elevated in cancer patients with VTE, and particularly, F1.2 was found to be a promising predictor of cancer-associated VTE.
静脉血栓栓塞症（VTE）是癌症患者发病和死亡的主要原因。人们一直在寻找有可能预测癌症相关VTE的生物标志物。其中，凝血酶生成标志物是一个可能的选择。本系统评价考察了三种广泛使用的凝血酶生成生物标志物：凝血酶原片段1.2（F1.2）、凝血酶 - 抗凝血酶复合物（TAT）和体外凝血酶生成，预测成年实体瘤和血液系统癌症患者发生VTE的能力。在PubMed和Embase数据库中检索相关研究，本评价符合系统评价和Meta分析的首选报告项目指南。每项研究都使用美国国立心肺血液研究所的质量评估工具进行评估。本评价方案已在国际前瞻性系统评价注册库（PROSPERO）上发表，标识符为CRD42022362339。本评价共纳入24篇论文：11篇报告F1.2的数据，9篇报告TAT的数据，12篇报告体外凝血酶生成的数据。纳入研究的质量评级从良好（= 13）、中等（= 8）到较差（= 3）不等，异质性较高。然而，F1.２、TAT复合物和体外凝血酶生成均与VTE的发生有关。这种关联在F1.2中最为明显。此外，F1.2的测定能够提高几种既定风险评估评分的准确性。总之，在患有VTE的癌症患者中发现凝血酶生成标志物升高，特别是F1.2被发现是癌症相关VTE的一个有前景的预测指标。
