Spiegelenberg Janneke P, De Laat-Kremers Romy, Roest Mark, de Laat Bas, van Gelder Marleen M H J, Tuladhar Anil M, Middeldorp Saskia, de Leeuw Frank-Erik, Leentjens Jenneke
Department of Functional Coagulation, Synapse Research Institute, Maastricht, the Netherlands; Department of Internal Medicine, Radboud university medical center, Nijmegen, the Netherlands.
Department of Data Analysis and Artificial Intelligence, Synapse Research Institute, Maastricht, the Netherlands.
J Thromb Haemost. 2025 Mar;23(3):978-988. doi: 10.1016/j.jtha.2024.12.002. Epub 2024 Dec 12.
Patients with ischemic stroke at a young age (18-50 years) have an increased long-term risk of recurrent ischemic events. Hypercoagulability may contribute to this high risk.
To investigate the associations between in vivo and ex vivo hemostatic parameters and recurrent ischemic events after an ischemic stroke or transient ischemic attack (TIA) at a young age.
We included patients with ischemic stroke or TIA between 1980 and 2010 from the prospective FUTURE cohort. Blood samples were collected in 2010, and patients were followed for recurrent ischemic events from 2010 to 2023. Pro- and anticoagulant markers and thrombin generation assay were measured. Thrombin dynamic analysis was used to study underlying pro- and anticoagulant processes. Hazard ratios (HRs) per standard deviation increase were assessed with cause-specific hazard models.
Of the initial cohort of 581 patients, 332 were eligible. The median time between the index event and 2010 was 7.6 years. During a mean follow-up of 6.5 years, 70 of 332 (21.1%) patients experienced a recurrent ischemic event. Lower antithrombin levels (adjusted HR, 0.77; 95% CI, 0.60-0.98) and higher fibrinogen levels (HR, 1.35; 95% CI, 1.04-1.73) were associated with higher risk of recurrent ischemic events. Plasma thrombin generation was not associated with recurrence. However, the thrombin decay constant (HR, 0.67; 95% CI, 0.51-0.87) was associated with a lower risk of recurrent ischemic events.
After an ischemic stroke or TIA at a young age, the thrombin decay constant, which reflects reduced protection against thrombin (low antithrombin) and decreased potential to inhibit thrombin (high fibrinogen), is associated with recurrent ischemic events.
年轻（18 - 50岁）缺血性卒中患者发生复发性缺血事件的长期风险增加。高凝状态可能导致这种高风险。
研究年轻缺血性卒中或短暂性脑缺血发作（TIA）后体内和体外止血参数与复发性缺血事件之间的关联。
我们纳入了前瞻性FUTURE队列中1980年至2010年间患有缺血性卒中和TIA的患者。2010年采集血样，并对患者从2010年至2023年进行复发性缺血事件随访。检测促凝和抗凝标志物以及凝血酶生成试验。采用凝血酶动力学分析研究潜在的促凝和抗凝过程。使用特定病因风险模型评估每标准差增加的风险比（HR）。
在最初的581例患者队列中，332例符合条件。索引事件与2010年之间的中位时间为7.6年。在平均6.5年的随访期间，332例患者中有70例（21.1%）发生了复发性缺血事件。抗凝血酶水平较低（校正HR，0.77；95%CI，0.60 - 0.98）和纤维蛋白原水平较高（HR，1.35；95%CI，1.04 - 1.73）与复发性缺血事件的较高风险相关。血浆凝血酶生成与复发无关。然而，凝血酶衰减常数（HR，0.67；95%CI，0.51 - 0.87）与复发性缺血事件的较低风险相关。
年轻缺血性卒中或TIA后，反映对凝血酶保护降低（抗凝血酶低）和抑制凝血酶潜力降低（纤维蛋白原高）的凝血酶衰减常数与复发性缺血事件相关。
