Fibrinolytic shutdown diagnosed with rotational thromboelastometry represents a moderate form of coagulopathy associated with transfusion requirement and mortality

Abstract

BACKGROUND Viscoelastic techniques have made it possible to describe specific fibrinolytic phenotypes (physiological, hyperfibrinolysis and shutdown) and to establish a relationship of these phenotypes with outcome. However, there remains a debate as to whether shutdown is a state of hypercoagulability or rather a coagulopathy with moderate fibrinolysis and fibrinogen consumption. OBJECTIVES Our objectives were to describe the relationship between fibrinolytic phenotypes and outcomes, and to report the effects of tranexamic acid (TXA) administration. DESIGN This was a retrospective analysis of prospectively acquired data from a trauma registry. SETTING An academic level 1 trauma centre in the Lyon Region, from March 2011 to December 2016. PATIENTS We included all injured patients who had a rotational thromboelastometry analysis at admission. Fibrinolytic phenotypes were determined according to the maximum lysis: shutdown less than 3%, physiological 3 to 15%, hyperfibrinolysis more than 15%. MAIN OUTCOME MEASURE Mortality at 24 h and at hospital discharge. RESULTS During the study period, 473 patients were included with the following phenotypes: physiological (344 patients, 73%), shutdown (107 patients, 23%) and hyperfibrinolysis (22 patients, 5%). There was an increase in injury severity, prothrombin time ratio, fibrin degradation products and transfusion requirements from the physiological to the shutdown and hyperfibrinolysis phenotypes. Prehospital TXA administration increased the rate of shutdown and decreased the maximum lysis value at admission. After adjustment, multivariate analysis showed that fibrinolytic phenotypes, but not TXA, were independently associated with an increased risk of early death and death before hospital discharge: shutdown [odds ratio (95% confidence interval)] 2.4 (1.2 to 4.8) and hyperfibrinolysis 67.9 (7.4 to 624.2). CONCLUSION The results of the current study suggest that shutdown, which is associated with injury severity and mortality, probably reflects a moderate form of coagulopathy and fibrinolysis rather than a hypercoagulopathy. Therefore, the observation of shutdown fibrinolysis on thromboelastography/rotational thromboelastometry should not lead to withholding but rather to the administration of TXA.

Is Tranexamic Acid Associated With Mortality or Multiple Organ Failure Following Severe Injury?

“…A majority of patients were male (335/420, 79.8%), of white race (227/420, 54.0%), and sustained blunt trauma (300/ 420, 71.5%). The median age was 37 (IQR: 26-55) years and the median ISS was 26 (IQR: [21][22][23][24][25][26][27][28][29][30][31][32][33]. Median time to TEG was 10.8 (IQR: 7.8-15.0) min.…”

“…Previous investigations report different rates of admission coagulopathy, as measured by INR, in patients with hyperfibrinolysis who received TXA (18,19). Even among the fibrinolysis phenotypes there are likely intrinsic differences in underlying post-traumatic coagulation (31)(32)(33).…”

“…While early TXA administration is advocated by a number of professional organizations as a method to minimize hemorrhage (8,11) and reduce mortality (1), recent statements advocate a more nuanced and sophisticated approach is necessary (13,22,38,40). It is becoming more apparent that even among fibrinolysis phenotypes there are significant differences in post-traumatic coagulopathy (22,(31)(32)(33). These differences must be critically investigated to further understand fibrinolysis and the role of TXA in the cellular-based dynamics of acute traumatic coagulopathy and resuscitation after traumatic injury.…”

Temporal Transitions in Fibrinolysis after Trauma: Adverse Outcome Is Principally Related to Late Hypofibrinolysis

“…Early low-maximum lysis is a poor determinant for the use of tranexamic acid since a significant proportion of patients will require a massive transfusion and die early; conversely, many other patients with low-maximum lysis on admission will require few blood products and revert to normal-maximum lysis at 24 h with low mortality. As described previously, early low-maximum lysis may signify an occult form of hyperfibrinolysis 9 or a moderate form of fibrinolysis and coagulopathy, 13,14 while a late low-maximum lysis state, associated with poor outcomes, may represent a true shutdown of the fibrinolytic system in response to a hypocoagulable state during bleeding. The underlying process of ROTEM hypofibrinolysis or the factors leading to it, rather than tranexamic acid per se, appears to determine the actual risk of developing multiorgan dysfunction syndrome.…”

“…Further biomarkers analyses and comparison with ROTEM patterns over time are required to elucidate the mechanisms underlying the fibrinolytic patterns, what ROTEM hypofibrinolysis represents in vivo, and whether each of the transition patterns described represent the same changes in the regulators of fibrinolysis. 13,14 Antifibrinolytics have been postulated to switch off normal levels of fibrinolysis, create a persistent fibrinolytic shutdown, and increase mortality and the incidence of multiorgan dysfunction syndrome and VTE, leading some institutions to limit tranexamic acid use to only those patients with ROTEM-diagnosed hyperfibrinolysis. 45,46 We have confirmed that prompt empiric administration of tranexamic acid is associated with reduced ROTEM hyperfibrinolysis and early deaths but importantly did not observe any increase in late mortality in patients who received tranexamic acid.…”