Gareth R Davies1,2, Suresh Pillai3, Matthew Lawrence1,2, Gavin M Mills3, Robert Aubrey3, Lindsay D'Silva1,2, Ceri Battle1, Rhodri Williams4, Rowan Brown4, Dafydd Thomas5, Keith Morris6, Phillip Adrian Evans7,8,9. 1. Haemostasis Biomedical Research Unit (HBRU), Morriston Hospital, Swansea, UK. 2. College of Medicine, Swansea University, Swansea, UK. 3. Emergency Department, ABM University Health Board, Swansea, UK. 4. College of Engineering, Swansea University, Swansea, UK. 5. Cardiac Intensive Care Unit, ABM University Health Board, Swansea, UK. 6. School of Applied Sciences, Cardiff Metropolitan University, Cardiff, UK. 7. Haemostasis Biomedical Research Unit (HBRU), Morriston Hospital, Swansea, UK. phillip.evans2@wales.nhs.uk. 8. College of Medicine, Swansea University, Swansea, UK. phillip.evans2@wales.nhs.uk. 9. Emergency Department, ABM University Health Board, Swansea, UK. phillip.evans2@wales.nhs.uk.
Abstract
PURPOSE: Sepsis and its progression are known to have a major influence on the coagulation system. Current coagulation tests are of limited use when assessing coagulation in sepsis patients. This study aims to assess the potential for a new functional biomarker of clot microstructure, fractal dimension, to identify changes in the mechanical properties of clot microstructure across the sepsis spectrum (sepsis, severe sepsis and septic shock). METHODS: A total of 100 patients that presented acutely to a large teaching hospital were included in this prospective observational study (50 sepsis, 20 severe sepsis and 30 septic shock) against a matched control of 44 healthy volunteers. Fractal analysis was performed, as well as standard markers of coagulation, and six plasma markers of inflammation. RESULTS: Fractal dimension was significantly higher in the sepsis and severe sepsis groups than the healthy control (1.78 ± 0.07 and 1.80 ± 0.05, respectively vs 1.74 ± 0.03) (p < 0.001), indicating a significant increase in mechanical clot strength and elasticity consistent with a hypercoagulable state. Conversely, fractal dimension was significantly lower in septic shock (1.66 ± 0.10, p < 0.001), indicating a significant reduction in mechanical clot strength and functionality consistent with a hypocoagulable state. This corresponded with a significant increase in the inflammatory response. CONCLUSIONS: This study confirms that clot microstructure is significantly altered through the various stages of sepsis. Of particular importance was the marked change in clot development between severe sepsis and septic shock, which has not been previously reported.
PURPOSE:Sepsis and its progression are known to have a major influence on the coagulation system. Current coagulation tests are of limited use when assessing coagulation in sepsispatients. This study aims to assess the potential for a new functional biomarker of clot microstructure, fractal dimension, to identify changes in the mechanical properties of clot microstructure across the sepsis spectrum (sepsis, severe sepsis and septic shock). METHODS: A total of 100 patients that presented acutely to a large teaching hospital were included in this prospective observational study (50 sepsis, 20 severe sepsis and 30 septic shock) against a matched control of 44 healthy volunteers. Fractal analysis was performed, as well as standard markers of coagulation, and six plasma markers of inflammation. RESULTS: Fractal dimension was significantly higher in the sepsis and severe sepsis groups than the healthy control (1.78 ± 0.07 and 1.80 ± 0.05, respectively vs 1.74 ± 0.03) (p < 0.001), indicating a significant increase in mechanical clot strength and elasticity consistent with a hypercoagulable state. Conversely, fractal dimension was significantly lower in septic shock (1.66 ± 0.10, p < 0.001), indicating a significant reduction in mechanical clot strength and functionality consistent with a hypocoagulable state. This corresponded with a significant increase in the inflammatory response. CONCLUSIONS: This study confirms that clot microstructure is significantly altered through the various stages of sepsis. Of particular importance was the marked change in clot development between severe sepsis and septic shock, which has not been previously reported.
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