68468-I (Arun Saini)Oct 1, 2022 - Sep 30, 2023Michael E. DeBakey Department of Veterans Affairs Medical Center
Role of Fibrin Clot Characteristics in Neuropsychological Performance after Traumatic Brain Injury
Role Description: Traumatic brain injury (TBI)-the "silent epidemic"-contributes to death and disability with an estimated 69 million people worldwide suffering TBI yearly. We and others have reported increased risk for neurocognitive decline, including stress-related psychopathology, memory loss, dementia, and Parkinson's syndrome in patients after TBI. Fibrinogen and fibrin deposition leading to microglia and astrocytes-driven neuroinflammation in the brain tissue has been implicated in neurocognitive decline after TBI. It is unknown if aberrations in fibrin clot characteristics (FCC), including fibrin clot function and structure, alter the fibrinogen/fibrin deposition and determine the severity of neurocognitive decline after TBI. Our preliminary data suggest an increase in fibrin clot porosity and a decrease in fibrin fibers density in patients after TBI compared to healthy controls. Our central hypothesis is that aberrations in FCC contribute to a decline in neuropsychological performance in patients after mild to moderate TBI.This novel translational study will demonstrate distinct FCC aberrations in patients with TBI and link FCC with neuropsychological performance. Identifying unique aberrations in FCC will provide novel strategies to treat patients with TBI to diminish neurocognitive decline.
67509 (Arun Saini)Jul 1, 2022 - Jun 30, 2023Texas Children’s Hospital
Fibrin Clot Characteristics in Thromboinflammation
Role Description: Sepsis, coronavirus disease 2019 (COVID-19), multisystem inflammatory syndrome (MIS-C), and hemophagocytic lymphohistiocytosis (HLH) cause clotting abnormalities in the bloodstream. Despite the economic burden and human toll, treatment of impaired clotting in these diseases remains suboptimal. Clotting leads to clot plugs in small and large blood vessels, which impede blood and nutrient supply to vital organs, leading to their failure and eventually death. It is well known that fibrin is the essential component of clots. Fibrin clot structure and function determine the properties of the formed clot. Abnormalities in fibrin clot formation and clot structure may lead to unstable clots. An abnormal fibrin network can make clots either excessively resistant to degradation or too fragile. Clots with fine fibrin (dense) mesh are slower to degrade than those with coarse fibrin (loose) mesh. We think fibrin structure and function abnormalities can be unique to the disease process. Understanding the differences and similarities in fibrin structure and function will allow us to understand the clotting burden in children with sepsis, COVID-19, MIS-C, and HLH. This knowledge will guide treatment to lower the clot burden for faster recovery of sick children with sepsis, COVID-19, MIS-C, and HLH.