Coagulation and Fibrinolytic Activity of Tenecteplase and Alteplase in Acute Ischemic Stroke

Abstract

Background and Purpose— We compared the fibrinolytic activity of tenecteplase and alteplase in patients with acute ischemic stroke, and explored the association between hypofibrinogenaemia and intracerebral hemorrhage. Methods— Venous blood samples from a subgroup of participants in the Alteplase–Tenecteplase Trial Evaluation for Stroke Thrombolysis (ATTEST) study were obtained at pretreatment, 3 to 12 hours, and 24±3 hours post-intravenous thrombolysis for analyses of plasminogen, plasminogen activator inhibitor-1, d -dimer, factor V, fibrinogen, and fibrin(ogen) degradation products, in addition to routine coagulation assays. Related sample Wilcoxon signed-rank tests were used to test the within-group changes, and independent Mann–Whitney tests for between-group differences. Results— Thirty patients were included (alteplase=14 and tenecteplase=16) with similar baseline demographics. Compared with baseline, alteplase caused significant hypofibrinogenaemia ( P =0.002), prolonged prothrombin time ( P =0.011), hypoplasminogenaemia ( P =0.001), and lower factor V ( P =0.002) at 3 to 12 hours after administration with persistent hypofibrinogenaemia at 24 hours ( P =0.011), whereas only minor hypoplasminogenaemia ( P =0.029) was seen in the tenecteplase group. Tenecteplase consumed less plasminogen ( P <0.001) and fibrinogen ( P =0.002) compared with alteplase. Conclusions— In patients with acute ischemic stroke, alteplase 0.9 mg/kg caused significant disruption of the fibrinolytic system, whereas tenecteplase 0.25 mg/kg did not, consistent with the trend toward lower intracerebral hemorrhage incidence with tenecteplase in the ATTEST study. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01472926.