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Title: Towards understanding coagulation system derangements in trauma
Author: Raza, Imran
ISNI:       0000 0004 7971 7935
Awarding Body: Queen Mary, University of London
Current Institution: Queen Mary, University of London
Date of Award: 2017
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Bleeding following trauma is exacerbated by coagulopathy and is a major cause for morbidity and mortality worldwide. The mechanisms influencing coagulopathy are not clear and require further exploration. A large pragmatic trial showed survival benefit from use of antifibrinolytics, suggesting fibrinolysis as a major component of coagulopathy. The overall aim of this work is to examine the incidence of fibrinolysis and magnitude of its activation in trauma, the protein mechanisms that may dominate in its modulation and to explore whether other coagulopathies may be important in trauma. A prospective cohort study of 325 injured trauma patients was carried out. Bloods samples were collected on arrival to ED and data collected on injury characteristics, demographics, blood component therapy and outcomes. An extension to the study included over 1500 patients recruited from 6 European centres in the same manner. Only 5% of patients showed evidence of ROTEM Lysis, however, 59% of patients had evidence of fibrinolytic activation (FA) in that they had PAP levels over 1500 mcg/L. FA correlated with severity of head, chest and extremity trauma. Having FA conferred a significantly higher chance of needing blood or blood products, having septic complications and longer hospital stay as well as significantly increased mortality compared to those with no FA. High levels of PAI-1 were found to be associated with lower levels of FA even when tPA was high. High levels of circulating TAFI or TAFIa were not associated with reduced markers of fibrinolysis suggesting they don't play a role in modulation. FXI depletion was associated with higher FA but its mechanism of action is unclear. Hierarchical clustering was successfully used to classify 1229 patients with a biological dataset of 21 variables into 6 distinct groups. These showed predominantly fibrinolytic patterns of coagulation derangement. One very small group showed signs of consumptive coagulopathy.
Supervisor: Not available Sponsor: Engineering and Physical Sciences Research Council (EPSRC)
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Trauma and Neuroscience ; coagulopathy ; fibrinolysis