Goal-directed Hemostatic Resuscitation of Trauma-induced Coagulopathy

González, Eduardo; Moore, Ernest E.; Moore, Hunter B.; Chapman, Michael P.; Chin, Theresa L.; Ghasabyan, Arsen; Wohlauer, Max V.; Barnett, Carlton C.; Bensard, Denis D.; Biffl, Walter L.; Burlew, Clay Cothren; Johnson, Jeffrey L.; Pieracci, Fredric M.; Jurkovich, Gregory J.; Banerjee, Anirban; Silliman, Christopher C.; Sauaia, Angela

doi:10.1097/sla.0000000000001608

Cited by 533 publications

(274 citation statements)

References 43 publications

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“…Our recent goal-directed resuscitation trial based on viscoelastic assays indicated a 50% reduction in mortality, but current thrombelastography (TEG) and thromboelastometry (ROTEM) assays do not include a measurement specific for platelet transfusion [7]. While these devices are capable of measuring platelet receptor inhibition to monitor antiplatelet therapy [8], their role in guiding platelets transfusions for TIC remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Platelet adenosine diphosphate receptor inhibition provides no advantage in predicting need for platelet transfusion or massive transfusion

Stettler

Moore

et al. 2017

Surgery

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Introduction Thrombelastography Platelet Mapping (TEG-PM) is a useful assay to assess antiplatelet therapy. Inhibited response to the ADP receptor on platelets occurs early following injury but recent work suggests this alteration occurs even with minor trauma. However, the utility of TEG-PM, specifically the percent of ADP receptor inhibition (%ADP-INH), in predicting outcomes and guiding platelet transfusion in trauma-induced coagulopathy (TIC) remains unknown. We assessed the role of %ADP-INH in predicting survival, requirement for massive transfusion or platelet transfusion in patients at risk for TIC. Methods TEG-PM was assessed in 303 trauma activation patients from 2014–2016 and in 89 healthy volunteers. %ADP-INH is presented as median and interquartile range (IQR). We compared the area under the receiver operating characteristic curve (AUROC) of %ADP-INH, platelet count, and rTEG Maximum amplitude (MA) for in-hospital mortality, massive transfusion (>10 RBC or death/6 hours, and platelet transfusion (>0 platelet units or death/6hrs). Results Overall, 35 (11.5%) patient died, 27 (8.9%) required massive transfusion and 46, platelet transfusions (15.2%). Median %ADP-INH was 42.5% (IQR: 22.4–69.1%), compared to 4.3 % (IQR: 0–13.5%) in healthy volunteers (p<0.0001). Patients that died, had a massive transfusion, or platelet transfusion had higher %ADP-INH than those that did not (p<0.05 for all). However, %ADP-INH did not add significantly to the predictive performance of MA or platelet count for any of the three outcomes, after adjustment for confounders. Subgroup analyses by severe traumatic brain injury, severe injury and requirement of RBCs showed similar results. Conclusion ADP receptor inhibition did not add predictive value to predicting mortality, massive transfusion, or platelet transfusion. Thus, the role of TEG-PM as a solitary tool to guide platelet transfusions in trauma requires continued refinement.

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Section: Introductionmentioning

confidence: 99%

Platelet adenosine diphosphate receptor inhibition provides no advantage in predicting need for platelet transfusion or massive transfusion

Stettler

Moore

et al. 2017

Surgery

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“…Prolonged clot initiation is an indication for plasma, abnormal dynamics of clot formation is a signifier for fibrinogen products, low clot strength is an indication for platelets, and increased fibrinolysis is an implication for antifibrinolytics. 8 Therefore, we used ROTEM measurements that focus on these aspects of clot formation and breakdown to develop a proposal for ROTEM-guided resuscitation. Studies have correlated EXTEM CT with coagulation factor activity; EXTEM Angle, EXTEM CFT, FIBTEM CA10, FIBTEM Angle, and FIBTEM MCF with fibrinogen level and function; EXTEM CA10 and EXTEM MCF with platelet-fibrinogen interactions; EXTEM CLI30, EXTEM CLI60, and EXTEM CT > APTEM CT or EXTEM MCF < APTEM MCF as evidence for fibrinolysis.…”

Section: Discussionmentioning

confidence: 99%

“…These results were achieved with the use of less plasma and platelet transfusions during the early phases of resuscitation. 8 Based on this, we would argue that either viscoelastic assay, ROTEM, or TEG, should be used instead of CCAs to guide resuscitation in injured patients. This is further illustrated by the fact that the PPV for aPTT and INR are no greater than 46.2% for either test.…”

Section: Discussionmentioning

confidence: 99%

“…8,10 The primary endpoint of this study was MT, defined as >10 units of red blood cells or death in first 6 h from injury based on findings previously published by our group. 11 …”

Section: Methodsmentioning

confidence: 99%

“…Furthermore, these results were achieved with the transfusion of less plasma and platelets during the early phases of resuscitation. 8 …”

Section: Introductionmentioning

confidence: 99%

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Rotational thromboelastometry thresholds for patients at risk for massive transfusion

Stettler¹,

Moore

Nunns³

et al. 2018

Journal of Surgical Research

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Background Goal-directed hemostatic resuscitation based on thrombelastography has a survival benefit compared to conventional coagulation assays. While thrombelastography transfusion thresholds for patients at risk for massive transfusion (MT) have been defined, similar cutoffs do not exist for the other commonly used viscoelastic assay, rotational thromboelastometry (ROTEM). The purpose of this study was to develop ROTEM blood product thresholds in patients at risk for MT. Methods ROTEM was assessed in trauma activation patients admitted from 2010 to 2016 (n = 222). Receiver operating characteristic curve analyses were performed to test the predictive performance of ROTEM measurements in patients requiring MT. The Youden Index defined optimal thresholds for ROTEM-based resuscitation. Results Patients who required MT (n = 37, 17%) were more severely injured. EXTEM clotting time (CT) was longer in patients with MT compared to non-MT (87 versus 64 s, P < 0.0001). EXTEM angle was shallower in MT patients compared to non-MT (54° versus 69°, P < 0.0001). Clot amplitude after 10 min (CA10) was less in MT compared to non-MT patients (30.5 versus 50 mm, P < 0.0001). Clot lysis index 60 min (CLI60) was lower in patients who had MT than non-MT (47 versus 94%, P = 0.0006). EXTEM CT yielded an area under the receiver operating characteristic curve (AUROC) = 0.7116 and a cut point of >78.5 s. EXTEM angle had an AUROC = 0.865 and a cut point of <64.5°. EXTEM CA10 had an AUROC = 0.858, with a cut point of <40.5 mm. CLI60 had an AUROC = 0.6788 with a cut point at <74%. Conclusions We have identified ROTEM thresholds for transfusion of blood components in severely injured patients requiring an MT. Based on our analysis, we propose plasma transfusion for EXTEM CT > 78.5 s, fibrinogen for angle <64.5°, platelet transfusion for CA10 < 40.5 mm, and antifibrinolytics for CLI60 < 74%.

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Early and Empirical High-Dose Cryoprecipitate for Hemorrhage After Traumatic Injury

Davenport,

Curry,

Fox

et al. 2023

JAMA

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ImportanceCritical bleeding is associated with a high mortality rate in patients with trauma. Hemorrhage is exacerbated by a complex derangement of coagulation, including an acute fibrinogen deficiency. Management is fibrinogen replacement with cryoprecipitate transfusions or fibrinogen concentrate, usually administered relatively late during hemorrhage.ObjectiveTo assess whether survival could be improved by administering an early and empirical high dose of cryoprecipitate to all patients with trauma and bleeding that required activation of a major hemorrhage protocol.Design, Setting, and ParticipantsCRYOSTAT-2 was an interventional, randomized, open-label, parallel-group controlled, international, multicenter study. Patients were enrolled at 26 UK and US major trauma centers from August 2017 to November 2021. Eligible patients were injured adults requiring activation of the hospital’s major hemorrhage protocol with evidence of active hemorrhage, systolic blood pressure less than 90 mm Hg at any time, and receiving at least 1 U of a blood component transfusion.InterventionPatients were randomly assigned (in a 1:1 ratio) to receive standard care, which was the local major hemorrhage protocol (reviewed for guideline adherence), or cryoprecipitate, in which 3 pools of cryoprecipitate (6-g fibrinogen equivalent) were to be administered in addition to standard care within 90 minutes of randomization and 3 hours of injury.Main Outcomes and MeasuresThe primary outcome was all-cause mortality at 28 days in the intention-to-treat population.ResultsAmong 1604 eligible patients, 799 were randomized to the cryoprecipitate group and 805 to the standard care group. Missing primary outcome data occurred in 73 patients (principally due to withdrawal of consent) and 1531 (95%) were included in the primary analysis population. The median (IQR) age of participants was 39 (26-55) years, 1251 (79%) were men, median (IQR) Injury Severity Score was 29 (18-43), 36% had penetrating injury, and 33% had systolic blood pressure less than 90 mm Hg at hospital arrival. All-cause 28-day mortality in the intention-to-treat population was 26.1% in the standard care group vs 25.3% in the cryoprecipitate group (odds ratio, 0.96 [95% CI, 0.75-1.23]; P = .74). There was no difference in safety outcomes or incidence of thrombotic events in the standard care vs cryoprecipitate group (12.9% vs 12.7%).Conclusions and RelevanceAmong patients with trauma and bleeding who required activation of a major hemorrhage protocol, the addition of early and empirical high-dose cryoprecipitate to standard care did not improve all cause 28-day mortality.Trial RegistrationClinicalTrials.gov Identifier: NCT04704869; ISRCTN Identifier: ISRCTN14998314

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Goal-directed Hemostatic Resuscitation of Trauma-induced Coagulopathy

Cited by 533 publications

References 43 publications

Platelet adenosine diphosphate receptor inhibition provides no advantage in predicting need for platelet transfusion or massive transfusion

Platelet adenosine diphosphate receptor inhibition provides no advantage in predicting need for platelet transfusion or massive transfusion

Rotational thromboelastometry thresholds for patients at risk for massive transfusion

Early and Empirical High-Dose Cryoprecipitate for Hemorrhage After Traumatic Injury

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