Early thromboelastography in acute traumatic coagulopathy: an observational study focusing on pre-hospital trauma care

Kaufmann et al. found that at hospital admission, the most represented hemostatic feature in an adult trauma population was hypercoagulation (included isolated shortening of R) [19]. Other TEG-versus-ROTEM comparison studies described a reduction in mean R value on early post-hospital admission TEG as well [20, 21].

In single TEG parameters analysis, the only R mean value showed a significant difference between on-scene and hospital arrival: in a large majority of patients was detected an R value decreasing.

Only another study searched for early post-traumatic coagulation abnormalities with TEG. This study was similar to ours, but our population presented more severe injuries [17]. The authors found no differences in TEG values between on-scene and hospital admission, except for a slight increase in MA, whose mean value remains in a normal range. In this study, R mean value at hospital admission was at the lower limit of the normal range. This finding could be due to a smaller magnitude of trauma, so the activation of coagulation was still setting up.

Almost one-fourth of patients had a worsening in TEG pattern from “on the scene” to hospital arrival. Despite this finding, there was no significant difference in standard coagulation parameters between the on-scene and hospital admission setting. This observation could be due to the time frame we chose for analysis. In our data, a worsening in TEG was mostly represented by a hypercoagulation pattern.

Gonzalez et al. suggested that R value could be analogous to PT and PTT. These latter values represent the activation of coagulation factors, even if they are not interchangeable to each other [22]. In literature, R value showed a strong correlation with PT and aPTT [23]. Despite significant changes in R values between the two groups which we had detected, we found no difference in variations of PT and PTT.

Hyperfibrinolysis was found in a few patients (11.3%) on the scene, and its prevalence showed a slight decrease at hospital admission (8.8%). Our prevalence of hyperfibrinolysis at hospital admission is smaller than reported by the literature [24, 25] using the same Ly30 cut-off. It may be due to differences in trauma patients, who are mostly hemorrhagic, requiring massive transfusions protocol in Chapman et al. [24]. Moore et al. enrolled more patients than us, so it could maybe affect the sensitivity of detection. We did not find an increase in hyperfibrinolysis from the trauma scene to hospital admission. Trauma patients are at increased risk of developing shock-induced hyperfibrinolysis due to pathological endothelial activation secondary to hypoperfusion and sympathoadrenal activation [26]. A few patients in our population presented more than two hypoperfusion markers on the trauma scene. The strategies to correct the hypoperfusion in the pre-hospital environment could probably correct the coagulation factors.

A small number of patients in our population developed TIC: 9.7% on the scene and 11.2% at hospital admission. As there is not a unique definition of TIC, different prevalences are reported depending on the cut-off value used. In 2003 Brohi et al. [4] published a large retrospective study, reporting that 24.4% of trauma patients had trauma acute coagulopathy (defined as PT > 18, aPTT > 60 s or TT > 15 s) at hospital admission. More recently, Davenport et al. found that 8% of trauma patients had PT ratio > 1.2. At the same time, Tauber et al. [16] and Hagemo et al. [15] using two different INR cut-off (1.5 and 1.2, respectively), found a coagulopathy in 14% and 11% of patients. In particular, Tauber et al. presented a population very similar to ours.

Patients with TIC did not exhibit a specific TEG pattern. They showed all possible kind of coagulation response to trauma: from normal to hyper- and hypocoagulant profile, to isolated shortening of R value. While prolonged INR and hypocoagulation move in the same direction, the finding of prolonged INR with normal or hypercoagulation pattern seems inconsistent. Standard laboratory tests detect the earliest initiation of clot formation [27], and PT/INR are extremely sensitive to clotting factors II, VII, and X [28]. Viscoelastic methods provide information about the whole coagulation process, exploring the interaction between all different components of the hemostatic system [29].

According to the cell-based paradigm of coagulation, TIC involved two critical players: platelets and endothelial cells. Immediately after trauma, the exposition of tissue factor from damaged tissues initiates coagulation through factor VII activation (the so-called “extrinsic pathway”). Factor VII is present in very low concentration in plasma and has the shortest half-life among all other coagulation factors [30]. Amplification and propagation are consequences of activation of endothelial cells, platelets, and other coagulation factors [27], also from the so-called “intrinsic pathway” [31]. The concomitance of two conditions may explain a prolonged INR in the presence of a hypercoagulation pattern. The initiation of coagulation determines the consumption of circulating factors to which INR measurement is sensitive. The amplification and propagation of coagulation strengthen the clot, whose “strength” is represented only by VHAs.

Our study was not designed to search for a correlation between laboratory tests and VHA in the diagnosis of TIC. Despite this, our findings suggest that even if the on-going activation of coagulation, conventional coagulation tests could be normal during early blood loss [14]. Furthermore, standard laboratory tests may suggest normal coagulation in patients with hypercoagulation pattern at VHA.

On the other hand we have to notice that our results showed a little number of patients with INR > 1.5 and normal TEG (and thus normal R). This sounds like a surprising discrepancy between PT/INR and R time. In a recent study of Sumislawski, the authors found that 20% of patients with abnormal INR have normal ACT on rapid-TEG (which is a substitute of R time of TEG); moreover, the case studies of these authors were more severely injured and had lower activity levels for all coagulation factors (except for VIII) respect to patients with isolated abnormal ACT. Severity of injury and factor II level were identified by authors as independent predictors of discordance between conventional and viscoelastic test.[32]. However, there is not a still clear explanation of this discrepancy but, as Sumislawki suggests, it may reflect differences in coagulation factor activities and thus different clinical phenotypes.

The different coagulation patterns which we detected did not show any correlation with NISS value at any time. Regardless of when the determination is made, in the case of severe trauma, many patients show a hypercoagulation profile. No difference in R values from the scene to the hospital admission for NISS 15–24 was detected. In NISS 25–40 patients, a moderate difference was found; the difference was very significant for NISS > 40 patients. In other words, the development of a hypercoagulation pattern is due to the severe trauma itself. More severe it is injury, greater is the magnitude of coagulation activation (R shortening).

Systolic arterial pressure and BE had not different distribution between patients whose TEG worsened and patients whose TEG remained stable or improved. At the same time, StO₂ < 75% was more present in the worsened TEG group. Thus, clinical features may not help to identify patients with ongoing post-traumatic hemostatic deranging early. There are a few studies that found a correlation between a hypoperfusion parameter such as BE, alone or with other clinical and laboratory features, and a single coagulation factor like blood fibrinogen [33, 34], but no one used VHA.

Hypercoagulation pattern at hospital admission was less represented in the group of patients who received more than 1000 mL of fluid for resuscitation than in the group of patients who received 1000 mL or less. No other TEG pattern presented different distribution between the two groups depending on the amount of fluid administration. Fluid therapy may have affected, through hemodilution, the real prevalence of hypercoagulant status at hospital admission. 10% of our patients presented hypocoagulation, hyperfibrinolysis, or a combination of the two patterns, on the scene. Furthermore, despite a liberal fluid administration, at hospital admission, these patterns were less represented (6%).

The fluid administration could not be sufficient to cause a dilutional coagulopathy. Furthermore, hemodilution alone is known to be not enough to set up coagulopathy [27]. Post-traumatic coagulation changes are expected to be pro-coagulant, at least in the very first phase [35]. If hypoperfusion is not counteracted, hypocoagulation develops mediated by thrombomodulin via activated protein C [36], and, at last, hypercoagulation takes place again, leading to thrombotic complications [37]. In our population, the first samples were collected very early, so it is not surprising to find mostly hypercoagulation pattern. However, the second samples were collected in a time frame in which we could have expected a rising number of hypocoagulant profile. This second event did not take place because of blood loss, and resulting hypoperfusion was probably counteracted with the pre-hospital fluid administration. This management could interrupt the pathway that would have led to hypocoagulation.

Most of our patients had only mild hypothermia on the scene, and at hospital admission as well. Mild hypothermia does not reduce enzyme activity [38, 39] and seems not to affect platelet activation. It could only cause platelet adhesion defects [38]. Moreover, hypothermia plays a role in coagulation alteration later in the clinical course of traumatized patients [36]. In our population, temperature alteration was too small to take part in early hemostatic derangement.