Exogenous Microparticles Bearing Tissue Factor Improve Outcome After Collagenase-Induced Intracranial Hemorrhage

 

“Time is brain” in the management of hemorrhagic strokes.  Intracerebral hemorrhage (ICH) is the most common type of spontaneous hemorrhagic stroke and is the most serious and least treatable form of stroke, and affects approximately 2 million people in the world per year. It is a life-threatening and disabling event, usually manifest as a rapidly expanding hematoma arising within the brain parenchyma. One in three patients die within the first month of onset, and survivors have varying degrees of residual disability and a high risk of recurrent hemorrhage and neurological complications. Unfortunately, there is still no medical treatment for acute ICH that is clearly beneficial. Research has shown that untargeted hemostatic therapy with rFVIIa reduced hematoma growth but came at the cost of an unacceptable rate of side effects. As such, targeted therapies that selectively promote hemostasis at the site of bleeding are warranted. Microparticles (MPs) derived from monocytes bearing tissue factor (TF) are known to accumulate during thrombus formation and promote thrombin generation in vivo.

Fanny Potzeha of the INSERM U1237, Physiopathology and Imaging of Neurological Disorders (PhIND) unit in Caen, France, stated that the administration of exogenous monocyte MPs bearing TF will activate coagulation at the site of bleeding, reducing hematoma growth in ICH. Via this abstract that they presented at the ISTH 2020 Virtual Congress, they sought to generate a large amount of procoagulant MPs to be used as hemostatic patches in preclinical models of ICH.

Upon generating large amounts of MPs from a monocytic cell line cultivated in bioreactors and stimulated with TNF, they performed an intrastriatal injection of collagenase VII to mice, promoting ICH. Subsequent to administration of the exogenous mMPs intravenously, hematoma volume was quantified by MRI at 24 hours, and neurological deficits were measured at both 4 and 24 hours post stroke. Potzeha reported that IV injection of exogenous MPs improved stroke outcome in a dose-dependent manner (prevented hematoma growth by 43% and improved neurological score at 4 and 24 hours) compared with control mice. She had concluded that exogenous MPs bearing TF improve outcome after collagenase-induced ICH by acting as intravascular patches, demonstrating the desired benefit in this “time is brain” situation.

Read the full abstract here.

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