Russell Mitesh Cerejo, MD
Desilles JP, Loyau S, Syvannarath V, Gonzalez-Valcarcel J, Cantier M, Louedec L, et al. Alteplase Reduces Downstream Microvascular Thrombosis and Improves the Benefit of Large Artery Recanalization in Stroke. Stroke. 2015
Dr. Jean-Philippe Desilles and colleagues studied the effects of IV tPA in downstream microvascular thrombosis. In their animal model they used rats with middle cerebral artery (MCA) occlusion for 60 minutes and then randomized them to IV tPA vs saline. They used Intravital fluorescence microscopy to visualize the circulating blood cells and fibrinogen. They also assessed for infarct volumes and neurological deficit. After sacrifice of the rats, they also assessed for patency of the microvasculature and plasma fibrinogen levels.
The authors found that immediately after occlusion of the MCA, there was early and pronounced adhesion of leukocytes and platelets that occurred almost exclusively in the venous compartment and persisted up to 1 hour post recanalization. There also was microthrombosis characterized by intraluminal deposition of fibrinogen developed in post-capillary micro vessels at sites of leukocyte and platelet accumulation, which caused complete cessation of blood flow.
Intravenous alteplase injection at 10 mg/kg 30 minutes after initiating MCA occlusion significantly reduced infarct size and also improved neurological deficits, evaluated 24 hours. In a subgroup of rats that were sacrificed before recanalization of the MCA occlusion showed that early administration of alteplase improves microvascular patency and stroke outcome indicating that alteplase exerts beneficial effects independently of its action on proximal arterial recanalization. Alteplase fibrinolytic activity induces a rapid and profound hypofibrinogenemia that prevents platelet aggregation and promotes disaggregation of freshly formed platelet aggregates.
These finding suggest that the use of IV alteplase treatment in eligible patients supplement endovascular therapy to improve the benefit of large artery recanalization, through targeting of downstream micro vascular thrombosis.