Model development and comparison of low hemorrhage-risk endoluminal patch thrombolytic treatment for ischemic stroke

Abstract

Clot dissolution drugs delivered into the systemic circulation can dissolve intracranial blood clots in 90 min with 20–50% hemorrhage rate. Immobilizing <5% of the intravenous dosage on an endoluminal patch can reduce the dissolution time to <20 min with negligible hemorrhage risk. The thrombus dissolution behavior in endoluminal patch thrombolytic treatment is modeled and compared with experimental results from a companion study. Analyses showed that the thrombus dissolution time decreases with increasing dosage, but the dissolution time reaches a dosage-independent minimum when uPA dosage on the patch is >800 IU. Model analyses showed that dissolution time in the plateau regime is controlled by diffusion. Further results showed that dissolution time could be reduced in this regime by reducing thrombus thickness. This suggests that a stented endoluminal thrombolytic >800 IU patch that compresses the thrombus to thin the clot thickness can help reduce dissolution time. This ultra-low transition dosage (i.e., 800 IU), compared to 0.6–2.4 million IU in conventional thrombolysis suggests that hemorrhage risk in endoluminal patch thrombolytic treatment is low. The low hemorrhagic-risk endoluminal patch can be considered for use in patients who are ineligible for conventional thrombolytic treatment because of high hemorrhagic treatment risk.