Project Summary Aneurysmal subarachnoid hemorrhage (aSAH) affects 30,000 people per year in the US and causes significant morbidity and mortality. Following this devastating event, patients are susceptible to secondary complications such as cerebral vasospasm and microthrombosis. Current treatments for these secondary mechanisms of brain injury are extremely limited, leaving patients exposed to cerebral ischemia and stroke. Due to the functional impairments caused by aSAH-induced ischemia, therapeutic clinical research remains active but has made little progress in the last 3 decades. The purpose of this research proposal is to determine the role of Haptoglobin (Hp) genotype to predict clinical outcome after aSAH. To support this project, several previous studies have demonstrated a link between Hp 2-2 genotype, increased incidence of vasospasm, and worse clinical outcome. In Aim 1, we will prospectively enroll patients, determine Hp genotype, and correlate this with clinical data including 3-month outcome to validate Hp as a genetic predictor for poor outcome. As a novel investigation, we will assess the inflammatory response as a function of Hp genotype. In Aim 2, coagulation markers will be assessed in patients using collected blood samples under the premise that platelet activation and hypercoagulability are a mechanism that mediates poor outcome. The goal of Aim 2 is to determine which pathway of coagulation is the best target for future pharmaceutical trials. This project will include training for Dr. Blackburn to further his development as a clinician scientist through a rigorous curriculum developed in the Center for Clinical and Translational Sciences, dedicated statistical training, and focused mentorship with experts in clinical trial, translational, and basic research. The project will be performed at the UTHealth Science Center – Memorial Hermann.

Project Narrative An estimated 2 percent of the population harbors an intracranial aneurysm, and every year more than 30,000 aneurysms will rupture in the U.S. Many who survive go on to have with crippling cognitive and motor deficits despite aggressive surgical and medical intervention. This project seeks to investigate the promising finding that Haptoglobin genotype predicts outcome after aneurysmal subarachnoid hemorrhage, and beyond this, novel mechanisms of inflammation and coagulation to determine future therapeutic targets.