Fibrinogen time course in acute ischemic stroke patients treated with intravenous thrombolysis with alteplase or tenecteplase.

Introduction: Limited data exist on intravenous thrombolysis (IVT) effect on fibrinogen depletion, and on possible associations between low fibrinogen levels and hemorrhagic complications, among acute ischemic stroke (AIS) patients.

Patients and methods: We conducted a prospective cohort study evaluating fibrinogen levels prior to IVT and at two prespecified timepoints following IVT end (2 and 24 h). Safety and efficacy outcomes were assessed. Fibrinogen depletion was defined as reduction < 200 mg/dl, or as reduction ⩾ 50% of baseline fibrinogen levels after 2 and 24 h from IVT. Furthermore, we conducted a systematic review and meta-analysis, comparing fibrinogen level changes from baseline to a timeframe of 2-12 h, and to 24 h post-IVT between patients receiving alteplase versus tenecteplase.

Results: One hundred and sixteen AIS patients, treated with IVT (alteplase = 81, tenecteplase = 35) were included in this study. Alteplase was associated with higher rates of fibrinogen depletion, observed in 2 (38% vs 0%; p-value < 0.001) and 24 h (26% vs 0%; p-value: 0.002) post-IVT, compared to tenecteplase. Three symptomatic intracranial hemorrhages (sICH) and one major extracranial bleeding were observed in patients receiving alteplase (two out of four with fibrinogen depletion) and one sICH without associated fibrinogen depletion was documented in the tenecteplase subgroup. Major hemorrhagic complications were numerically higher in patients with fibrinogen depletion (6.5% vs 3.5%, p = 0.609). Fibrinogen depletion was documented in 50% of alteplase-treated patients complicated with sICH or major extracranial bleeding and in 0% of respective tenecteplase-treated patients. Two cohorts were included in the meta-analysis. Mean relative changes of fibrinogen levels from baseline to a timeframe of 2-12 h post-IVT (RoM: 9.84; 95% CI: 9.63-10.05) were significantly higher in patients receiving alteplase.

Discussion and conclusions: Fibrinogen depletion was observed only in AIS patients receiving alteplase and was associated with numerically higher rates of major hemorrhagic complications. These findings require independent confirmation in larger, international cohort studies.