Redefining postinjury fibrinolysis phenotypes using two viscoelastic assays

Abstract

INTRODUCTION: Fibrinolysis was initially defined using rapid thrombelastography (rTEG). The cutoffs for the pathologic extremes of the fibrinolytic system, hyperfibrinolysis and shutdown, were both defined based on association with mortality. We propose to redefine these phenotypes for both TEG and for rotational thrombelastometry, the other commonly used viscoelastic assay. METHODS: Rotational thrombelastometry, rTEG, and clinical data were prospectively collected on trauma patients admitted to an urban Level I trauma center from 2010 to 2016. Hyperfibrinolysis was defined as the Youden index from EXTEM-clot lysis index 60 minutes after clotting time (CLI60) and rTEG-fibrinolysis 30 minutes after achieving MA (LY30) for predicting massive transfusion (>10 red blood cell units, or death per 6 hours after injury) as a surrogate for severe bleeding. Patients identified as having hyperfibrinolysis were then removed from the data set, and the cutoff for fibrinolysis shutdown was derived as the optimal cutoff for predicting mortality in the remaining patients. RESULTS: Overall, 216 patients (median age, 36 years (interquartile range, 27–49 years), 82% men, 58% blunt injury) were included. Of these, 16% required massive transfusion, and 12.5% died. Rapid thrombelastography phenotypes were redefined as hyperfibrinolysis: rTEG-LY30 greater than7.7%, physiologic rTEG-LY30 0.6% to7.6%, and shutdown rTEG-LY30 less than 0.6%. EXTEM-CLI60 fibrinolysis phenotypes were hyperfibrinolysis CLI60 less than 82%, physiologic (CLI60, 82–97.9%), and shutdown (CLI60 > 98%). Weighted kappa statistics revealed moderate agreement between rotational thrombelastometry– and rTEG-defined fibrinolysis (k = 0.51; 95% confidence interval, 0.39–0.63), with disagreement mostly in the shutdown and physiologic categories. CONCLUSION: We confirmed the U-shaped distribution of death related to fibrinolysis system abnormalities. Both rTEG LY30 and EXTEM CLI60 can identify the spectrum of fibrinolytic phenotypes, have moderate agreement, and can be used to guide hemostatic resuscitation. LEVEL OF EVIDENCE: Diagnostic study, level III.

The role of evidence-based algorithms for rotational thromboelastometry-guided bleeding management

“…However, it is still under debate whether prophylactic or therapeutic administration of TXA should be performed in hospitals with access to viscoelastic testing [145][146][147][148][149][150][151][152][153][154][155]. Physiologic fibrinolysis and fibrinolysis shutdown are defined in ROTEM as an EXTEM LI60 82-97.9% and ≥ 98%, respectively [156].…”

Traumatic-Induced Coagulopathy as a Systems Failure: A New Window into Hemostasis

“…72 In another bi-institutional cohort study including 2,540 severe trauma patients, Moore's group reported fibrinolysis shutdown in 46% of patients followed by a physiological state (36%) and hyperfibrinolysis (18%). 37,77 They further showed an independent association between fibrinolysis shutdown and mortality compared with physiological fibrinolysis. Their diagnostic criteria for the spectrum of fibrinolysis states was based on TEG LY30: shutdown 0.8%, physiological fibrinolysis of 0.9 to 2.9%, hyperfibrinolysis 3% at admission.…”

“…3,32 What has emerged in recent years is that it is no longer sufficient to rely solely on plasmatic prothrombin time, international normalized ratio, or activated partial thromboplastin time to diagnose coagulopathy and guide treatment. 3,[33][34][35][36][37] Other trauma trials suggest that similar limitations may also apply to relying exclusively on single point parameters from viscoelastic methods (e.g., clot times and indices of clot lysis). [38][39][40] Fig .…”

“…9,27,[63][64][65][66][67] This bleeding phenotype, known as hyperfibrinolysis, is a common feature of eTIC and carries with it a high mortality rate (> 30%). 3,37,63 In some patients, the condition can be partially corrected with the antifibrinolytic tranexamic acid (TXA). [68][69][70][71] However, if TXA is administered to a trauma patient with no active fibrinolysis, it may increase the risk of posttraumatic venous thromboembolism and further increase morbidity and mortality.…”

“…77 In 2019, Stettler et al also confirmed the Ushaped distribution of mortality and the three major fibrinolysis phenotypes, and that TEG and ROTEM (with slightly modified cutoffs) demonstrated good agreement. 37 Moore's shutdown analysis following hyperfibrinolysis has generated a huge amount of interest and controversy. Cardenas et al reanalyzed the Pragmatic, Randomized, Optimal Platelet, and Plasma Ratios (PROPPR) trial data and found that fibrinolysis shutdown may be a classification error related to the insensitivity of TEG and that a low TEG LY30 does not reflect "shutdown of fibrinolysis with hypercoagulability, but rather a coagulopathic state of moderate fibrinolysis with fibrinogen consumption and platelet dysfunction" that is associated with poor outcomes.…”