High Thrombin Generation after Acute Ischemic Stroke or Transient Ischemic Attack Is Associated with a Reduced Risk of Recurrence: An Observational Cohort Study

Thrombin is increasingly recognized to be of importance for cardiovascular disease. The aim of this study was to investigate the prognostic value of thrombin generation variables in a cohort of patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA). Thrombin generation potential measured by calibrated automated thrombogram (CAT) and prothrombin fragment F1+2 was determined in the acute and convalescent phases for a cohort of 190 patients with AIS/TIA. Microvesicle (MV)-induced thrombin generation potential was determined for a subset of patients using modified CAT. Primary outcome was a composite of fatal and nonfatal AIS or myocardial infarction as documented in Swedish registers during a total follow-up of 986 patient-years. Hazard ratios (HRs) were calculated using Cox regression based on variable median split. Peak thrombin and endogenous thrombin potential (ETP) above median in the acute phase were associated with a reduced risk of primary outcome after adjustment for cardiovascular risk factors, HR: 0.50 (0.27-0.92), p =0.026 and HR: 0.53 (0.28-0.99), p =0.048, respectively. F1+2 was lower in patients than in healthy controls but not associated with outcome. MV-induced peak thrombin above median in the acute phase was associated with recurrent AIS, unadjusted HR: 2.65 (1.03-6.44), p =0.044. Contrary to expectation, high thrombin generation potential is associated with a reduced risk of recurrent ischemic event in patients with AIS/TIA. Low ETP/peak thrombin combined with high MV-induced peak thrombin can potentially identify patients at high risk of recurrence.

Automated summary

This study investigated the prognostic value of thrombin generation variables in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA). The results showed that high thrombin generation potential may reduce the risk of adverse outcomes, but also be associated with recurrent AIS.