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Biological mechanisms and individual variation in fibrinolysis after major trauma
  1. Timothy J Coats1,
  2. Mohamed Morsy1,2
  1. 1 Department of Cardiovascular Sciences, Academic Unit of Emergency Medicine, University of Leicester, Leicester, Leicestershire, UK
  2. 2 Department of Anaesthesia and Intensive Care, Faculty of Medicine, Minia University, El Minia, Egypt
  1. Correspondence to Dr Timothy J Coats, Cardiovascular Sciences, University of Leicester, Leicester LE1 5WW, UK; tc61{at}


Objective To understand more about the individual variation in the time course of fibrinolysis following major injury and to assess the potential for stratification of trauma patients for tranexamic acid (TXA) therapy.

Methods A historical dataset (from 2004) was used, consisting of samples from 52 injured patients attended by a medical prehospital system. Blood samples were taken at the incident scene, on arrival in the emergency department, 2.5 hours after hospital arrival and 5 hours after hospital arrival. From the study database, we extracted values for tissue-type plasminogen activator (tPA; an activator of fibrinolysis), one of the plasminogen activator inhibitors (PAI-1; as a natural inhibitor of fibrinolysis) and D-dimer (as a marker of the extent of fibrinolysis).

Results The changes over time in median tPA and PAI-1 were mirror images, with initial high tPA levels which then rapidly decreased and low initial PAI-1 levels which slowly increased. There were high levels of fibrinolytic activity (D-dimer) throughout. This pattern was present in patients across a broad range of injury severities.

Conclusions After major trauma, there seems to be an early ‘antifibrinolytic gap’ with the natural antifibrinolytic system lagging several hours behind the natural profibrinolytics. An early dose of exogenous antifibrinolytic (TXA) might have its effect by filling this gap. The finding that tPA and subsequent clot breakdown (illustrated by D-dimer formation) are raised in a broad range of patients, with little correlation between the initial fibrinolytic response and markers of injury severity, may be the reason that TXA is effective across a broad range of injured patients.

  • trauma
  • major trauma management
  • haematology
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  • Contributors Both authors were involved in each stage of the development of the idea, extraction and analysis of the data and writing of the manuscript.

  • Funding The original data collection was funded by the Special Trustees of Barts and the Royal London Hospital with ethics approval from the East London and The City Research Ethics Committee.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request. Data are available through the corresponding author.

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