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Volume 22 Supplement 1

London Trauma Conference 2013

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Reduction of the natural Activated protein C pathway activity significantly prevents coagulopathy in a murine model of acute traumatic coagulopathy


Acute traumatic coagulopathy (ATC) identified in the first hour of trauma patients is associated with worse outcomes and increased risk of death [1]. Identification of critical coagulation pathways involved in ATC is important for future targeted drug discovery. Previous studies have demonstrated an activation of the thrombomodulin-protein C pathway during ATC [2]. We examined the effect of reduced thrombomodulin generation in an experimental model of ATC.


Both wild type (WT) and modified Knock-in TM pro/pro mice (TMKI) were subjected to trauma (laparotomy with muscle injury and bilateral tibia-fibula fracture) and haemorrhage (40± 5% of estimated blood volume) to a target mean arterial blood pressure of 30 ± 5 mmHg. This model was developed to elicit coagulopathy as a response to trauma and bleeding thus mimicking the coagulopathy present in the injured patient. The animals were kept euthermic and were not resuscitated. After 60 minutes blood samples were taken and analysed via thrombelastometry tests.


All animals were shocked when compared with controls (lactate ≥ 7 mg/dL and ≤ 3 mg/dL; p<0.001). After trauma and haemorrhagic shock (THS), WT mice developed a significant coagulopathy, as measured by a reduction in clotting amplitude at 5 minutes (CA5’) (THS time 0 vs time 60 = 46.7± 1.37 vs 27.6±2.57 mm, p<0.0002) and in maximal clot firmness (MCF) (THS t0 vs t60 =62.7±1.1 mm vs 46± 3.3 mm, p<0.001). In the TMKI group, which entails a 1000 fold reduction in aPC production there was a correction of the coagulopathy (CA 5’: TMKI time 0 vs time 60 = 42.6± 2.3 vs 41.6±1.5 mm, p<0.0002 and MCF (TMKI t0 vs t60 =56.8±2 mm vs 55.1± 1 mm, p<0.001.


Severe trauma shock induced a significant coagulopathy characterised by the generation of fragile clots. The reduction in activated protein C generation encompassed an improvement in the experimental coagulopathy therefore the protein C pathway seems to play an important role in acute traumatic coagulopathy.


  1. Brohi K, Cohen M, Ganter M, et al: Acute coagulopathy of trauma: hypoperfusion induces systemic anticoagulation and hyperfibrinolysis. J Trauma. 2008, 64: 1211-1217. 10.1097/TA.0b013e318169cd3c.

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  2. Chesebro B, Rahn P, Carles M, et al: Increase in activated protein C mediates acute traumatic coagulopathy in mice. Shock. 2009, 32: 659-665. 10.1097/SHK.0b013e3181a5a632.

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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

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Guerreiro, M., Tremoleda, J.L., Frith, D. et al. Reduction of the natural Activated protein C pathway activity significantly prevents coagulopathy in a murine model of acute traumatic coagulopathy. Scand J Trauma Resusc Emerg Med 22 (Suppl 1), O6 (2014).

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