Dynamic alterations of novel thrombotic molecular markers in acute ischemic stroke patients after intravenous thrombolysis: a retrospective cohort study

Background: Novel thrombotic molecular markers include the thrombin-antithrombin complex (TAT), plasmin inhibitor-plasmin complex (PIC), thrombomodulin (TM), and tissue plasminogen activator-plasminogen activator inhibitor-1 complex (t-PAIC). These molecular markers facilitate the early assessment of coagulation and fibrinolysis system functions, as well as vascular endothelial injury; however, their clinical application following intravenous thrombolysis for acute ischemic stroke (AIS) remains unclear. Therefore, our study aims to evaluate the dynamic levels of these novel thrombosis-related molecular markers within 24 hours after intravenous thrombolysis in patients with AIS and analyze their relationship with patients outcome. Methods: We conducted a retrospective cohort study based on the data of 77 patients with AIS who underwent alteplase intravenous thrombolysis between November 2022 and February 2024. Novel thrombotic markers were evaluated at four time points: prior to thrombolysis, 1 hour after thrombolysis, 6 hours after thrombolysis, and 24 hours after thrombolysis. Based on the modified Rankin scale (mRS) score at day 90 post-discharge, patients were categorized into the good outcome group (mRS ≤ 1) and the poor outcome group (mRS > 1). Stepwise multivariate logistic regression was employed to analyze the association between 90-day functional outcomes and the measured variables. The area under the receiver operating characteristic curve (AUC) was utilized to assess the predictive ability of novel thrombotic markers. Results: Our study demonstrated that, compared to the poor outcome group, the good outcome group exhibited significant lower serum TAT levels both prior to thrombolysis and at 6 hours post-thrombolysis (all p  < 0.05), and serum TM and t-PAIC levels were also significantly elevated in the good outcome group at 1 hour, 6 hours, and 24 hours following thrombolysis (all p  < 0.05). Stepwise logistic regression analysis indicated that increased serum TM and t-PAIC levels at 24 hours post-thrombolysis were protective factors for a good 90-day outcome. The AUC values of TM, t-PAIC, and TM combined with t-PAIC for predicting 90-day functional outcomes were 0.918 (sensitivity 80.0%; specificity 85.7%), 0.658 (sensitivity 91.4%; specificity: 45.2%), and 0.984 (sensitivity: 97.1%; specificity 97.6%), respectively. Conclusion: Novel thrombotic molecular markers might serve as indicators for the early monitoring of dysfunction in the coagulation-fibrinolysis system and endothelial injury following intravenous thrombolysis for AIS. TM and t-PAIC exhibit predictive value regarding the outcome of intravenous thrombolysis in AIS, providing insights for future research on the protective role of TM in AIS.