Fibrinogen Depletion Coagulopathy and Hemorrhagic Transformation in Acute Ischemic Stroke Treated With Bridging Therapy

Abstract

Background: Hemorrhagic transformation (HT) frequently occurs in acute ischemic stroke patients with a large vessel occlusion undergoing endovascular therapy (EVT), significantly impacting functional outcomes. We aimed to determine whether an early fibrinogen depletion coagulopathy (FDC) was associated with HT following bridging therapy (ie, intravenous thrombolysis [IVT] followed by EVT), and to identify its associated factors.

Methods: We retrospectively analyzed prospectively collected data from 296 patients with acute ischemic stroke with a large vessel occlusion who underwent EVT alone or bridging therapy, with fibrinogen levels measured both before baseline imaging and at the start of the EVT procedure. FDC was defined as a fibrinogen level <2.0 g/L at the start of the EVT procedure, with an absolute decrease >1.0 g/L from baseline. The primary outcome was the occurrence of any HT at 24 to 36 hours. Secondary outcomes included symptomatic HT, parenchymal hematomas, and 3-month mortality. The relationships between FDC and outcomes were studied using multivariable logistic regression analyses, adjusting for relevant confounders. We also studied baseline characteristics associated with FDC occurrence.

Results: Of the 296 patients enrolled, 102 (34.5%) experienced HT, and 54 (18.2%) developed FDC. FDC was strongly associated with IVT use (53/161 [32.9%] versus 1/135 [0.7%] in IVT-treated and non-IVT-treated patients, respectively; P<0.01). In patients receiving bridging therapy, FDC occurrence was independently associated with any HT (adjusted odds ratio, 2.33 [95% CI, 1.11-4.91]), symptomatic HT (adjusted odds ratio, 3.35 [95% CI, 1.20-9.40]), parenchymal hematomas (adjusted odds ratio, 2.87 [95% CI, 1.14-7.24]), and 3-month mortality (adjusted odds ratio, 3.82 [95% CI, 1.47-9.93]). None of the 26 patients who received tenecteplase experienced FDC, compared with 53 of 135 (39.3%) patients treated with alteplase (P<0.01).

Conclusions: Following bridging therapy, FDC is a frequent event associated with increased risks of any HT, symptomatic HT, parenchymal hematomas, and 3-month mortality. FDC did not occur following IVT with tenecteplase in our cohort, suggesting that the fibrin specificity of thrombolytic agents may play a pivotal role in its development.

Keywords: fibrinogen; fibrinolytic agents; hemorrhage; stroke; thrombectomy.