Early Fibrinogen Depletion and Symptomatic Intracranial Hemorrhage After Reperfusion Therapy

Background and Purpose- We aimed to thoroughly investigate the relationship between early fibrinogen depletion and symptomatic intracranial hemorrhage (sICH) in patients receiving reperfusion therapy including intravenous thrombolysis (IVT) with or without endovascular thrombectomy (EVT). Methods- This study included 1135 stroke patients with baseline and follow-up fibrinogen levels at 2 hours after the beginning of alteplase infusion for those with IVT only or immediately after the end of EVT for those with combined IVT and EVT. Patients received alteplase up to 9 hours after the onset or on awakening based on automated perfusion imaging. sICH was ascertained using ECASS II (The Second European-Australasian Acute Stroke Study) criteria. Δfibrinogen was calculated as follow-up fibrinogen minus baseline fibrinogen. Results- In patients with IVT only, baseline fibrinogen level was 3.36±0.94 g/L and decreased to 2.47±0.80 g/L at 2 hours after the beginning of alteplase infusion. In patients with IVT followed by EVT, baseline fibrinogen level was 3.35±0.82 g/L and decreased to 2.52±0.83 g/L immediately after the end of EVT. sICH was observed in 44 (3.9%) patients. The extent of Δfibrinogen was associated with sICH in patients with IVT only (odds ratio, 1.929; 95% CI, 1.402-2.654; P<0.001) and in those with IVT followed by EVT (odds ratio, 1.765; 95% CI, 1.135-2.743; P=0.012). Conclusions- An early decrease in fibrinogen levels was related to sICH after reperfusion therapy with alteplase. More fibrin-specific thrombolytic agents are warranted to be tested in acute ischemic stroke patients. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT03367286.