Department of Clinical Research, Copenhagen University Hospital Amager and Hvidovre, Hvidovre, Denmark.
Emergency Department, Copenhagen University Hospital Amager and Hvidovre, Hvidovre, Denmark.
Phlebology. 2023 Oct;38(9):577-598. doi: 10.1177/02683555231186681. Epub 2023 Aug 24.
Post-thrombotic syndrome (PTS) is a frequent chronic complication of deep venous thrombosis (DVT). Biomarkers are potentially valuable clinical tools for handling PTS. The purpose of this review was to examine which biomarkers are associated with the development of PTS in adults with lower extremity DVT.
We performed a systematic review of all English language prospective studies of biomarkers and PTS published in PubMed and EMBASE. Studies were included if diagnosing DVT by diagnostic imaging and assessing PTS by clinical scales, for example, the Villalta scale. Biomarkers of thrombophilia and pathological clot properties were not assessed. Data was reported qualitatively.
15 prospective studies were included. Studies varied widely in study design and methods of data analysis. Forty-six different biomarkers were examined, with seven being measured in two or more studies. The most frequently studied biomarkers were D-dimer, CRP, and IL-6. Associations between PTS and D-dimer were predominantly significant, while results on CRP and IL-6 were inconsistent. ICAM-1 was consistently associated with PTS in all studies and at all timepoints. IL-10 was significantly related to PTS development in the largest study and at all time points. Adiponectin, tPA, HRG and TAFI, MMP-1 and -8, and TIMP-1 and -2 were significantly associated with PTS in single studies.
(1) Further research on biomarkers and PTS is clearly warranted. (2) Significant differences in study designs made it difficult to draw reliable conclusions regarding individual biomarkers. We suggest the implementation of a standardized framework for the study of biomarkers and PTS, to make comparison of future studies more feasible. (3) D-dimer, ICAM-1, IL-10, MMP-1 and 8, TIMP-1, TIMP-2, and adiponectin are clinical biomarkers of particular interest to include in future studies of PTS. Large scale systemic quantitative proteomic analyses of DVT patients could help identify novel biomarkers of interest in PTS-patients.
血栓后综合征（PTS）是深静脉血栓（DVT）的常见慢性并发症。生物标志物是处理 PTS 的潜在有价值的临床工具。本综述的目的是检查哪些生物标志物与下肢 DVT 成人 PTS 的发展相关。
我们在 PubMed 和 EMBASE 上系统地检索了所有以英文发表的关于生物标志物与 PTS 的前瞻性研究。如果通过诊断成像诊断 DVT 并通过临床量表（例如 Villalta 量表）评估 PTS，则纳入研究。未评估血栓形成倾向和病理性血栓特性的生物标志物。数据以定性方式报告。
共纳入 15 项前瞻性研究。研究在研究设计和数据分析方法上差异很大。共检查了 46 种不同的生物标志物，其中 7 种在两项或更多研究中进行了测量。研究最多的生物标志物是 D-二聚体、CRP 和 IL-6。PTS 与 D-二聚体之间的相关性主要具有统计学意义，而 CRP 和 IL-6 的结果不一致。ICAM-1 在所有研究和所有时间点均与 PTS 一致相关。在最大的研究和所有时间点，IL-10 与 PTS 发病显著相关。在单个研究中，脂联素、tPA、HRG 和 TAFI、MMP-1 和 -8 以及 TIMP-1 和 -2 与 PTS 显著相关。
（1）显然需要进一步研究生物标志物和 PTS。（2）研究设计的显著差异使得难以就个别生物标志物得出可靠的结论。我们建议实施一个标准化框架来研究生物标志物和 PTS，以便更可行地比较未来的研究。（3）D-二聚体、ICAM-1、IL-10、MMP-1 和 -8、TIMP-1、TIMP-2 和脂联素是 PTS 未来研究中特别有意义的临床生物标志物。对 DVT 患者进行大规模系统性定量蛋白质组学分析可能有助于确定 PTS 患者中感兴趣的新型生物标志物。
