Thromboelastography in Trauma June 5, 2015

What is TEG? TEG is a functional assay which measures the blood’s ability to form a clot Measures clot formation via the tensile strength of fibrin-polymer-platelet complex First developed in Germany in 1948

How does it work? The patient’s whole blood sample is placed in a small cup at 37° C A metal pin goes into the center of the cup The machine slowly spins the cup As the clot forms, it connects the inside of the cup with the metal pin, and the energy used to move the cup is transferred to the pin A wire connected to the pin measures the strength of the clot and creates a computerized tracing J Periop US App Tech. 2012;1(1). 

http://emmedonline.com/emergency_medicine/thromboelastogram

Parameters R (reaction time): Time from activation of the clotting cascade to the formation of fibrin Depends on coagulation factors Treat short R with coumadin Treat prolonged R with coagulation factor replacement/ FFP

Parameters k: Time from formation of fibrin to a defined amplitude Represents speed of clot formation

Parameters α (angle): Measures the speed of fibrin build-up and cross-linking Depends on fibrinogen Treat a low angle with fibrinogen replacement/ cryoprecipitate

Parameters MA (maximum amplitude): Represents strength of the fibrin clot correlated to platelet function (80% platelets/20% fibrinogen) Depends on platelets Treat a low MA with platelets Treat an increased MA with ASA/Plavix

Parameters LY30: Percentage decrease in amplitude 30 minutes after the MA is measured Measures degree of fibrinolysis May consider treatment with antifibrinolytics or anticoagulants (primary vs. secondary)

Examples Int J Periop US Appl Tech. 2012;1(1).

J Periop US App Tech. 2012;1(1). 

Types of TEG Standard TEG Rapid TEG Heparinase cup Platelet mapping Coagulation initiated with kaolin Rapid TEG Coagulation initiated with tissue factor; ACT (activated clotting time) instead of r-value Heparinase cup TEG is run twice, once with heparinase and once without; compare two curves and if no change then no effect from heparin Platelet mapping Baseline TEG compared to two additional patient samples with maximal stimulation of platelets with AA and ADP; computer calculates difference in MA as % inhibition

Trauma induced coagulopathy 1981 to ̴2007: “Bloody vicious cycle" Acidosis from tissue injury and shock, hypothermia from fluid infusions and exposure, and hemodilution from blood and fluid administrations (“lethal triad”) Leads to secondary development of trauma induced coagulopathy https://www.aacc.org/publications/cln/articles/2014/july/coagulation 

Trauma induced coagulopathy 2007: Distinct primary disorder, cell-based model Initiation (tissue factor on cells), amplification (platelet activation), propagation (thrombin generation) Hypoperfusion leads to excess activation of protein C, which inhibits thrombin generation, impairs clot formation, and degrades any clots that have formed Inten Care Med. 2011;37. 

Trauma induced coagulopathy Occurs in 30% of trauma patients Most common preventable cause of postinjury mortality Associated with: 8x increased 24 hour mortality 4x increased total mortality longer ICU and total hospital stay increased risk for renal insufficiency and multiple organ failure longer need for ventilatory support tendency towards increased lung injury Classical coagulation tests (PT/PTT) are only weakly predictive of bleeding in trauma patients, do not predict extent of bleeding, and results are not available rapidly enough Inten Care Med. 2011;37. 

Trauma induced coagulopathy J Trauma. 2003;54(6). 

Guidelines We recommend that routine practice to detect post-traumatic coagulopathy include the measurement of international normalised ratio (INR), activated partial thromboplastin time (APTT), fibrinogen and platelets. INR and APTT alone should not be used to guide haemostatic therapy (Grade 1C). We suggest that thrombelastometry also be performed to assist in characterising the coagulopathy and in guiding haemostatic therapy (Grade 2C). Crit Care. 2010;14:R52.

TEG in trauma induced coagulopathy Turn around time Diagnosis of TIC Prediction of blood product use Prediction of mortality Critical Care. 2014;18.

Turn around time

Turn around time J Trauma. 2009 Apr;66(4).

Turn around time Prospective study of 272 trauma patients Early r-TEG (activated clotting time, k-time) available within 5 minutes Late r-TEG (α angle, MA) within 15 minutes Standard clotting tests (PT/INR/PTT/platelet count) within 48 minutes (p=<0.001) J Trauma. 2011;71(2).

Diagnosis of trauma induced coagulopathy

Diagnosis of trauma induced coagulopathy Observational study of 69 blunt trauma patients 7 hypocoagulable by TEG (mean ISS 28.6) 1 hypocoagulable by PT/PTT 6/7 hypocoagulable patients received blood 45 hypercoagulable by TEG (mean ISS 13.1) 17 normal by TEG (mean ISS 3.7) Only ISS and TEG were predictive of blood product use in the first 24 hours (p=<0.05) J Trauma. 1997;42(4). 

Diagnosis of trauma induced coagulopathy 20 traumatic brain injury patients versus 10 healthy controls TBI patients have a lower platelet count (180,000 per microliter vs 256,000 per microliter in healthy controls, p<0.005) and reduced platelet response to AA on platelet mapping (mean 22% vs 73% in healthy controls, p<0.001) J Neurotrauma. 2007;24(11). 

Diagnosis of trauma induced coagulopathy Review from 1970 to 2013 to determine diagnostic accuracy of TEG or ROTEM for diagnosing TIC 3 studies using ROTEM and 0 studies using TEG 300, 90, and 40 patients Clot amplitude was the only potential indicator 5 min: 70-96% sensitivity and 86-58% specificity 10 min: 100% sensitivity and 70% specificity 15 min: 88% sensitivity and 100% specificity TIC was defined as INR of 1.2 or greater or 1.5 or greater Cochrane Library. 2015;2. 

Prediction of blood product usage

Prediction of blood product usage Observational study of 69 blunt trauma patients TEG, PT, PTT, revised trauma score, ISS 6 patients received transfusion in first 24 hours Only ISS and TEG were predictive of blood product use in the first 24 hours (p=<0.05) J Trauma. 1997;42(4). 

Prediction of blood product usage Retrospective study of 44 penetrating trauma patients INR, PT, and PTT were increased in 39%, 31%, and 37% but did not correlate with use of blood products (p>0.05) MA correlated with blood product use as well as platelet count (p,0.01) Patients with reduced MA (23) used more blood products and had lower platelet counts and hematocrit. J Trauma. 2008;64(2). 

Prediction of blood product usage Prospective study of 272 trauma patients Rapid TEG available in trauma bay ACT predicted RBC (p < 0.001), plasma (p < 0.001) and platelet (p <0.001) transfusions within 2 hours of arrival ACT > 128 sec predicted massive transfusion > 10 units in first 6 hours (p = 0.01) ACT < 105 sec predictions patients who did not receive any transfusions in first 24 hours (p = 0.04) J Trauma. 2011;71(2).

Mortality

Mortality 23 trauma patients 5 patients with hyperfibrinolysis Higher injury severity score (75 vs 20, p<0.05) Higher INR (8.2 vs 1.3, p<0.05) Lower fibrinogen (0.0 vs 2.2 g/L, p<0.05) Higher mortality rate (100% vs 11%, p<0.05) Br J Anaesth. 2008;100(6). 

Mortality Prospective study of 795 major trauma patients Elevated Ly30 was an independent predictor of mortality Combined with GCS ≤ 8, SBP ≤ 90mmHg, Hgb < 11g/dL, and BE < -6mEq/L to create 5-variable 24 hour mortality predictive model (AUROC 0.88, HL goodness-of-fit 0.90) All parameters available within 30 minutes. J Trauma. 2014 May;207(5). 

Mortality Retrospective review 131 trauma patients with pelvic fracture TEG R > 6 was independently associated with death independent of injury severity (OR 16, P=0.0001); death rate 52% No significant association between traditional coagulation tests (PT/INR/PTT) and death rate Orthopedic Surgery 2015;7(1). 

Additional points

Additional points What about hypercoagulable TEG results? What does this mean in the trauma setting?

Hypercoagulable TEG in cardiac surgery patients 124 patients scheduled for CABG Divded into two groups: TEG-hypercoagulable and TEG-normocoagulable 3 months post-op, all had CT to evaluate graft patency 359 grafts, 186 TEG-HC and 173 TEG-NC No difference in bypass graft occlusion (p=0.9) Rate of major adverse cardiovascular and cerebral events significantly higher in TEG-HC (30% vs 9%, p=0.004) Scandinavian Cardiovascular Journal 2013;47(2). 

TEG-based blood administration algorithms Studies in other populations (cardiac surgery) have found some benefit to TEG-based blood administration algorithms, does this apply to trauma patients?

TEG-guided transfusions in pediatric surgery patients 78 pediatric cardiac surgery patients Conventional transfusion vs algorithm/TEG guided transfusion for 12 hours post-op TEG-guided transfusion significantly reduced post-op bleeding (9 vs 16 mL/kg, p<0.001), PRBC transfusion requirement (11 vs 23 mL/kg, p=0.005), and ICU stay (60 vs 71 h, p=0.014) Platelet and plasma transfusions were similar, but occurred earlier in TEG-guided group Brit J Anesth. 2015;114(1). 

Special populations

Special populations Effect of differing baseline TEG results in special populations, and potential impact during trauma: Neonates Alcohol intoxication Use of newer anticoagulants Uremia

Neonates Limited data in neonates, particularly no data on premature neonates Small number of healthy infants showed age dependent accelerated initiation and propagation of coagulation despite prolonged standard coagulation tests; clot firmness and fibrinolysis similar to adults J Maternal-Fetal and Neonatal Med 2012;25(s4). 

Effect of alcohol 35-50% of trauma patients are acutely intoxicated Alcohol has little effect on standard coagulation tests, transfusion requirements, or outcome, but does affect TEG results: Prolonged R time (5.91 vs 4.43 min, p=0.013) Decreased angle (66.5 vs 70.2 degrees, p=0.001) Trend toward decreased MA (63.44 vs 64.93 mm, p=0.063) J Trauma Acute Care Surg 2014;77(6). 

Newer anticoagulants It is unclear how newer anticoagulants may or may not affect TEG parameters

Uremia Baseline TEG r-time, k-time, α angle, and MA are hypercoagulable in uremic patients compared to controls (p<0.05), and fibrinolysis was decreased in uremic patients J Clin Anesth. 1997;9(6). 

Summary Many small, single center, observational studies of TEG in trauma TEG results are available more rapidly than standard coagulation tests Some evidence to suggest TEG may allow for early diagnosis of trauma induced coagulopathy and may predict blood product usage and mortality, but associations with specific parameters are variable Randomized trials are lacking It’s unclear how baseline differences in TEG in various populations might impact TEG results during trauma