Target condition being diagnosed
Trauma-induced coagulopathy (TIC) can be defined as an impairment of blood clotting occurring early after injury (Frith 2010). A diagnosis of TIC on admission carries a mortality rate amongst patients of up to 50%, and is often associated with increased burdens of transfusion, greater risks of organ injury and septic complications, and longer stays in critical care (Brohi 2003; MacLeod 2003; Maegele 2007). Worldwide, trauma is the leading cause of mortality and disability in adults under the age of 36 years old (Hess 2009) and 40% of all trauma deaths (in the UK) are as a result of haemorrhage (Frith 2010), whilst shock and coagulopathy upon admission have both been independently associated with massive transfusion and increased mortality (Spinella 2009). Equally in the combat setting, bleeding is the largest cause of death on the battlefield (Holcomb 2007).
Various terms such as TIC, ‘acute traumatic coagulopathy' (ATC) and ‘acute coagulopathy of trauma shock’ are used to describe these early coagulation changes. None of these terms have taken particular precedence and all are widespread within the trauma literature. For the purposes of this review we will use the term ‘trauma-induced coagulopathy’ (TIC) to describe the hypocoagulable changes that occur within the first 24 hours following injury due to a variety of different and highly interlinked causes, i.e. hypoperfusion, ongoing bleeding and consumption of clotting factors, haemodilution, acidosis, hypothermia and ATC. In the absence of embedded clinical consensus, the coagulopathic range we will be using is based on pro-thrombin time ratio (PTr) /International Normalized Ratio (INR). Anyone with a PTr/INR count of above 1.2, or above 1.5, is considered coagulopathic (further detail is given in the section on Reference standards). These figures were reached through review of the literature and discussion by the report authors, including experts in haematology and trauma medicine.
The aetiology of coagulopathy associated with trauma is not fully understood. In non-trauma situations, blood clots form through a chain of actions; first, platelets form a sticky clump (or ‘white clot’) on the blood vessel wall at the site of injury. This clot is weak, but soon a cascade of clotting proteins generates fibrin, a protein which meshes the platelets and some red blood cells together to produce a far stronger clot (or ‘red clot’). This process is called coagulation, but it can become disordered - and this happens in around a quarter of trauma patients. The underlying reasons for this disruption are still unknown, but the combination of tissue damage and shock are contributory factors, as is the presence of hypoperfusion through severe blood loss (Barts & The London 2011).
Early recognition of the nature of the clotting defect has been acknowledged as increasingly important to guide replacement of clotting factors alongside blood volume maintenance and red cell replacement. However, there are no validated methods to effectively guide therapy. This leads to both over-transfusion and under-transfusion, reduction in efficacy, increased wastage and exposure to risk. These issues can be exacerbated in disasters where timely availability of blood and component therapy is vital but severely resource constrained.
Standard blood tests - i.e. the ‘current tests’ - are performed as soon as possible on arrival to hospital (see Figure 1). There is no hierarchy of tests performed at admission, but rather a group of tests - i.e. activated partial thromboplastin time (APTT), PTr/INR and full blood count (FBC). The choice of these tests is very variable and follows local hospital practice. In some centres, especially across Europe, thromboelastography (TEG)/thromboelastometry (ROTEM) are standard tests. In the UK the use of TEG and ROTEM is increasing, but has - up until now - mainly been in the experimental and research fora.
Traditional measures of clotting such as platelet count, bleeding time, PT and APTT have some limitations in the context of managing trauma. Amongst these,
platelet count provides numbers of how many platelets are present but gives no information about how they function;
bleeding time measured through the application of a cuff also assesses platelet function, but is impractical in the bleeding patient;
fibrinogen readings allow measurement of fibrinogen levels in the blood, but this is specific to fibrinogen and does not give an overall indication of coagulopathic function;
PT and APTT only provide a measure of time before initial thrombin generation, are performed on platelet-poor plasma, were designed to evaluate clotting factor deficiencies (not acquired coagulopathy), and are known to be poor predictors of bleeding in these circumstances (Dzik 2004).
In addition, evidence has suggested that APTT and PT are not able to provide an indication of when a patient is in a hypercoagulable state (Park 2009).
Despite these weaknesses, in practical terms PT remains the current standard of practice.
Newer global haemostatic function technologies such as TEG and ROTEM enable ‘point of care’ measurement, using whole blood samples, of the initiation and progress of coagulation as well as final clot strength and lysis and the dynamics of clot formation. For the purposes of this study, TEG and ROTEM are being envisaged as a replacement test for traditional clotting tests. Both tests are currently used in routine clinical practice as both a diagnostic tool and to guide treatment.
Both TEG (trademark of Haemonetics Corporation, USA: www.haemonetics.com) and ROTEM (trademark of TEM International GmbH: www.rotem.de) work by measuring shear elastic modulus during clot formation and subsequent fibrinolysis. In both tests the whole blood sample is placed in a sample cup or ‘cuvette’ into which a cylindrical pin is immersed, leaving a small gap between the bottom of the pin and the base of the cuvette. The subsequent movement of the blood (designed to emulate sluggish circulation) is where the main difference lies between the two methods. When the sample blood begins to clot (i.e. fibrin begins to form, measured as clotting time or ‘time to clot’), the movement of the pin becomes restricted with increasing firmness and this kinetic is transferred to the machinery of the TEG or ROTEM unit.
The next stage of the coagulation process is platelet aggregation, where platelets build in the blood vessel walls at the site of injury, and fibrin binds to the platelets which then forms a stronger clot, measured in both TEG and ROTEM in shear elasticity units as ‘clot stability’. Eventually lysis – or clot break down – is measured, and a graphic is produced which represents haemostatic performance at all these stages: clotting time, clot formation, clot stability and lysis (see Appendix 1).
Whilst both TEG and ROTEM measure clotting time, clot formation, clot strengthening, amplitude of clot, maximum strength of clot, and clot lysis, they use slightly different terms or lettering to designate these features. We draw out these differences in detail in Appendix 2 and Table 1.
|Clotting time (period to 2 mm amplitude)|
R (reaction time)
N (whole blood) 4 to 8 min
N (Cit, kaolin) 3 to 8 min
CT (clotting time)
N (Cit, in-TEM) 137 to 246 s
N (Cit, ex-TEM) 42 to 74 s
|Clot kinetics (period from 2 to 20 mm amplitude)|
N (WB) 1 to 4 min
N (Cit, kaolin) 1 to 3 min
CFT (clot formation time)
N (Cit, in-TEM) 40 to 100 s
N (Cit, ex-TEM) 46 to 148 s
|Clot strengthening (alpha angle)|
α (slope between r and k)
N (WB) 47° to 74°
N (Cit, kaolin) 55° to 78°
α (slope of tangent at 2 mm amplitude)
N (Cit, in-TEM) 71° to 82°
N (Cit, ex-TEM) 63° to 81°
|Amplitude (at set time)||A||A|
MA (maximum amplitude)
N (WB) 55 to 73 mm
N (Cit, kaolin) 51 to 69 mm
MCF (maximum clot firmness)
N (Cit, in-TEM) 52 to 72 mm
N (Cit, ex-TEM) 49 to 71 mm
N (Cit, fib-TEM) 9 to 25 mm
|Lysis (at fixed time)||CL30, CL60||LY30, LY60|
This systematic review will form part of the evidence for a wider research programme which aims to improve outcomes for severely injured bleeding trauma patients, designed around the principle that early identification of patients who present with a trauma-induced coagulopathy and effective, directed therapy will lead to improved outcomes, reduced complications, rationalised transfusions, reduced costs to the National Health Service (NHS) and a reduced logistical burden to the military and humanitarian organisations (such as the Red Cross) within austere combat environments. However, these tests require proper evaluation. Test accuracy studies have been conducted amongst evaluations thus far and should be systematically reviewed.
To complement this review we also propose to carry out a systematic review of prognosis studies linking measures from TEG/ROTEM with patient outcome. This cannot be included in The Cochrane Library at present.