FunctIonal coaGulation and HemosTasis after IntraCerebral Hemorrhage (FIGHT-ICH)

Project Summary Stroke is the 5th leading cause of death in the United States and spontaneous intracerebral hemorrhage (ICH) is a hemorrhagic stroke subtype which carries the highest morbidity and mortality of all strokes. Ongoing bleeding, otherwise known as hematoma expansion (HE), occurs within the initial 24 hours in up to 40% of these patients and is the strongest driver of worse neurological outcomes. Consequently, acute ICH treatments largely focus on the rapid diagnosis and treatment of coagulopathy to prevent HE and improve outcomes. However, accurate laboratory assessments to identify coagulopathy relevant for HE are currently lacking. Up to 20% of patients with “normal” traditional plasma-based coagulation testing can go on to encounter HE, suggesting limitations in these current coagulation testing paradigms. These limitations have led to treatment trials using empiric therapy approaches. However, these trials did not improve outcomes, and even caused harm. These trials have highlighted that certain therapies carry inherent risks, offsetting any potential benefits. This emphasizes a critical knowledge gap in better identifying patients vulnerable to HE and the ability to provide precise and targeted therapies for their coagulopathies. Using whole blood viscoelastic hemostatic assays (VHAs), a contemporary clinical coagulation assay, we identified that patients that encounter HE do in fact have coagulopathy related to impaired coagulation kinetics detectable at the bedside, not seen using traditional tests. However, our data suggests that these coagulopathies relevant for HE are not uniform and may differ between common ICH subgroups. Thus, if we can identify specific coagulation drivers related to our VHA and HE observations amongst these different ICH subgroups, we would be able to provide tailored treatments to these specific processes and patients. These approaches will likely improve outcomes by preventing HE more effectively, while limiting risks and side effect exposures from unnecessary treatments. Subsequently, our proposal seeks to perform a multimodal assessment of coagulation using traditional clinical coagulation assays (PT/PTT/INR, platelet count, fibrinogen), contemporary clinical whole blood VHAs, and research-based coagulation proteomic analyses in ICH patients to provide a broad, translational approach to assess bedside tools (VHAs) to diagnose coagulopathy while also assessing specific proteins driving these coagulopathies. Our proposal has a distinct advantage of leveraging established expertise at the intersection of laboratory medicine and large ICH research networks with the ability to provide rigorous neuroimaging analyses for HE, neurological assessments, and laboratory-based assessments of coagulation. Our project will fill an important gap in ICH treatment paradigms by identifying novel approaches to diagnose coagulopathy relevant for both HE and poor ICH outcomes, while identifying novel treatment targets to test in future ICH studies.