Evaluation of the Role of Endogenous Factor XIII as a Determinant of Bleeding-Related Outcomes and Death Among Severely Injured Patients

Uncontrolled bleeding is the number one preventable cause of death after traumatic injuries. The body limits blood loss by reducing clot destruction with coagulation factors such as factor XIII (FXIII). Lower serum FXIII levels can cause reduced clot stability and premature clot breakdown. We hypothesize that lower FXIII levels result in worse bleeding-related outcomes and death. To test the hypothesis, we first examined the available evidence concerning FXIII levels and its supplementation and adverse outcomes. Then, we evaluated whether lower FXIII concentration was associated with bleeding-related outcomes and death in severely injured patients. Lastly, in a cohort of severely bleeding patients, we sought to ascertain whether lower baseline FXIII levels were associated with massive transfusion and whether they were different FXIII trajectories within the first 24 hours post-injury. We found that the available evidence concerning FXIII is scarce, low-quality, and prone to confounding bias. We also identified key knowledge gaps that should be addressed in future research endeavours, such as defining the target population, improving the quality of evidence, and addressing FXIII treatment uncertainties (transfusion trigger, doses, testing modality, etc.). Furthermore, we found that baseline FXIII levels had an inconsistent association with bleeding-related outcomes in severely injured patients and were not associated with a composite of massive transfusion or death due to bleeding in severely bleeding patients. Lastly, we identified distinct FXIII trajectories within 24 hours post-trauma; the group of patients with initial low FXIII levels and an early increase within 4 hours post-injury had lower 24-hours and mortality due to bleeding than the remaining groups despite a high-injury severity clinical profile. Overall, this thesis work found that reduced FXIII levels do not appear to be a key driver of hemorrhagic risk in severely injured patients; however, we were limited by generally small sample sizes, few FXIII measurements, and cohorts of patients where tranexamic acid was not consistently provided. Future research is needed in the form of a prospective international longitudinal cohort study to determine the natural history and potential clinical relevance of FXIII in a large, contemporary and diverse patient population of severely injured patients.

Department dc:contributor.department

Medical Science

Year dc:date.issued

2025

Author dc:creator

• Gomez Builes, Johana Carolina

Advisors dc:contributor.advisor

• Baker, Andrew J
• Sholzberg, Michelle

• Bleeding
• Coagulation factor XIII
• Hemostasis
• Trauma

Handle dc:identifier.uri

https://hdl.handle.net/1807/145114

OAI identifier oai:identifier

oai:utoronto.scholaris.ca:1807/145114