Received Date: November 17, 2016; Accepted Date: January 20, 2017; Published Date: January 30, 2017
Citation: Brazinova A, Mauritz W (2017) Early Use of Thrombelastometry is Associated with Improved Outcomes after Severe Traumatic Brain Injury. J Blood Lymph 7: 153. doi: 10.4172/2165-7831.1000153
Copyright: © 2017 Brazinova A, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Introduction: Posttraumatic coagulopathy worsens outcomes of patients with severe traumatic brain injury (TBI). This study aimed to investigate whether the early use of thrombelastometry (TEM) was associated with better outcomes after TBI. Methods: Between 3/2002 and 4/2012 17 Austrian centers enrolled TBI patients into 2 observational studies that focused on effects of guideline compliance (n=400) and on prehospital and early hospital management (n=777), respectively. Data on trauma severity, clinical status, prehospital and hospital treatment, and outcomes were collected prospectively. Information on use or non-use of TEM was missing in 278 cases. Data from patients with hopeless prognosis and patients with moderate TBI were excluded. Two groups of patients were created: the “TEM group” (TEM used within the first 2 h after admission, n=211) and the “no-TEM group” (211 matched patients selected from 610 possible cases). Demographic data and data on trauma severity, treatment and outcome were compared. Logistic regression models, corrected for the effects of age, Glasgow Coma Scale (GCS) scores, and Injury Severity Score (ISS) were constructed. A p-value of <0.05 was considered statistically significant. Results: Age, sex, trauma mechanisms, and treatment were not significantly different. The “TEM group” had higher trauma severity. However, hospital mortality was significantly lower (20% vs. 31%, p=0.01) Logistic regression revealed that use of TEM, age, ISS and GCS score had significant influences upon hospital mortality and long-term outcome. Conclusions: The early use of TEM is associated with significantly better outcomes after severe TBI. Level of evidence: III, retrospective therapeutic study.
Traumatic brain injury severe; Traumatic brain injury moderate; Traumatic brain injury outcome; Traumatic brain injury coagulopathy; Thrombelastometry
Traumatic brain injury (TBI) is a major health and socioeconomic problem. The burden of TBI is highest in low-income and middleincome countries due to road traffic incidents and predominantly affects young individuals. In high-income countries TBI occurs mainly due to falls in the elderly [1,2]. The goals of the management of TBI patients are to prevent secondary insults to the injured brain and to transport the patients to a neurotrauma center for definitive treatment [3-5]. Assessment of clinical status, intubation, adequate ventilation, and fluid resuscitation are important treatment options to prevent and treat hypoxia, hypoventilation, and hypotension [5,6]. Coagulopathy is an important problem after TBI , and thrombelastometry (TEM) has been used to assess coagulation after trauma [8-10] as well as after TBI [11,12]. The goal of this retrospective analysis of prospectively collected data was to assess whether the early use of TEM would lead to improved outcomes as suggested in an earlier study on trauma patients .
Between 2001 and 2012 the International Neurotrauma Research Organization (INRO, a non-governmental research organization, founded 1999; based in Vienna, Austria) coordinated two observational projects that focused on Austrian patients with TBI. Projects enrolled TBI patients without age limit, with multiple trauma, and patients with low Glasgow Coma Scale (GCS) scores. Both projects collected data on epidemiology, prehospital care, and hospital treatment. First one focused on patients with severe TBI and analyzed the effects of guideline-based treatment  between 3/2002 and 6/2005 5 centers enrolled 400 patients. The second project included patients with moderate and severe TBI; between 3/2009 and 4/2012 16 centers enrolled 777 patients. Both projects were approved by the appropriate local Ethical Committees. All patients admitted to the participating hospitals were included if they fullfiled the following criteria for moderate/severe brain trauma
• GCS of 8 or less following resuscitation for severe TBI, GCS of 12 to 9 following resuscitation for moderate TBI.
• GCS score deteriorating to 8 or less within 48 h of injury for severe TBI, or to 12 to 9 for moderate TBI.
Due to the purely observational design of the projects informed consent of the patients was not mandatory; however, all patients that regained consciousness gave written permission to use their data for scientific purposes. The data were collected in 17 Austrian centers. All centers were able to provide state-of-the-art patient management. According to the prognostic IMPACT (International Mission for Prognosis and Analysis of Clinical Trials in TBI) core model  the centres achieved outcomes that were better than predicted . Treatment in the field was provided by emergency physicians or paramedics, it included rapid examination with documentation of vital signs (GCS score, pupillary status, blood pressure, heart rate, oxygen saturation). Rapid sequence intubation facilitated by hypnotics, sedatives and relaxants, ventilation, treatment of hemorrhage, and fluid resuscitation were done as appropriate. After admission each patient was examined by a trauma team and a computed tomography (CT) scan was done. In centers where TEM was available the decision to use or not to use it was made by the attending physicians. The patients then underwent surgery as appropriate and/or were admitted to the intensive care unit (ICU). Neurosurgery was provided by neurosurgeons (6 centers) or by trauma surgeons (11 centers) who had the option of consulting neurosurgeons for more difficult cases. The specialty of the surgeon had no impact on outcomes of the patients . Intensive care was provided by anesthesiologists in cooperation with neuro or trauma surgeons.
Basic demographic data of the patient, cause and location of trauma, prehospital status and treatment, mechanism and severity of trauma (Abbreviated Injury Score [AIS], Injury Severity Score [ISS]), results of CT scans, results of lab testing, use of TEM, and data on surgical procedures and outcomes were recorded in databases developed by INRO. Prehospital data were documented by emergency physicians/paramedics, and were then transferred into the databases. CT scans were interpreted by neurosurgeons, trauma surgeons and radiologists, and the following findings were entered into the CT sheet of the database: detailed data on basal cisterns, midline shift, main findings, and the Rotterdam CT score . Data on duration of various treatments, on complications, and on outcomes were collected at discharge from the ICU and at hospital discharge. Information on status and location was recorded at 6 months after injury by phone calls to the patients and/or their relatives; in some cases the Glasgow Outcome Scale (GOS) score (18) was recorded at patients’ follow-up visits to the centers. The full database had 1177 files. For this study, we used data of severe TBI patients only: 211 patients where TEM was used (“TEM group”) were closely matched with 211 cases where TEM was not used. Ranked by importance, the criteria for selection were age, GCS score, pupillary reactivity, AIS of the region “head”, ISS, and CT scan criteria (patency of basal cisterns, midline shift, predominant injury). The selected 211 cases formed the “no-TEM group”. Data on trauma mechanism, trauma severity, CT findings, treatment, and outcomes were retrieved for each patient in both groups. “Unfavorable outcome” was defined as a GOS score of <4 at 6 months after trauma.
Data are given as means with standard deviations, medians with interquartile ranges (IQR), or as proportions. Two-tailed t-test, Fisher’s exact test, Chi-square test, and analysis of variance were done as appropriate to identify differences between the groups. To check for associations with outcomes we constructed logistic regression models for ICU and hospital death and unfavorable long-term outcome where the effects of TEM use were corrected for age, GCS scores, and ISS. A p-value of < 0.05 was considered statistically significant.
Demographic data and data on trauma severity are given in Table 1. Age, sex, and injury mechanisms were not different. “TEM group” had higher rates of prehospital hypotension and hypoxia, higher ISS and lower GCS. No differences were observed regarding treatment (Table 2). Outcomes were better in the “TEM group”: ICU mortality was lower (18 vs. 26%, not significant), hospital mortality was lower (20 vs. 31%, significant), and the rate of unfavorable outcome was lower (39 vs. 46%, not significant). The multivariate analysis revealed that use of TEM was significantly associated with improved ICU, hospital, and long-term outcomes. Older age, higher ISS and lower GCS score were associated with worse outcomes (Table 3).
|Variable||No-TEM group||TEM group||Total||P-value|
|Age (mean, SD)||48.1 (22.4)||47.5 (22.7)||47.7 (22.5)||0.774|
|Sex (N, % male)||165 (78%)||148 (70%)||313 (74%)||0.076|
|Injury mechanism (N, %)||0.235|
|Traffic related||83 (41%)||79 (38%)||162 (40%)|
|Fall<3m||60 (30%)||59 (28%)||119 (29%)|
|Fall>3m||21 (10%)||28 (14%)||49 (12%)|
|Sports||16 (8%)||20 (10%)||36 (9%)|
|Violence||10 (5%)||3 (1%)||13 (3%)|
|Other||12 (6%)||19 (9%)||31 (8%)|
|Enrollment GCS (median, IQR)||4 (3-8)||3 (3-6)||3 (3-7)||<0.01|
|ISS (mean, SD)||26 (11.7)||28.6 (14.8)||27.3 (13.4)||0.048|
|AIS head & neck (mean, SD)||4.1 (0.7)||4 (0.8)||4.1 (0.8)||0.202|
|Pupils (N, %)||0.433|
|One reactive||28 (14%)||17 (9%)||45 (11%)|
|Both reactive||155 (76%)||155 (80%)||310 (78%)|
|None reactive||21 (10%)||20 (10%)||41 (10%)|
|Not assessable||1 (1%)||2 (1%)||3 (1%)|
|Prehospital hypoxia (N, % Yes)||5 (9%)||37 (22%)||42 (19%)||0.037|
|Prehospitalhypotension (N, % Yes)||9 (5%)||18 (11%)||27 (7%)||0.044|
SD: Standard Deviation; GCS: Glasgow Coma Scale; ISS: Injury Severity Score; AIS: Abbreviated Injury Score
Table 1: Demographics and trauma severity.
|Variable||No-TEM group||TEM group||Total||P-value|
|Prehospitalintubation (N, % Yes)||191 (91%)||186 (88%)||377 (89%)||0.528|
|Secondary transport (N, % Yes)||31 (15%)||26 (13%)||57 (14%)||0.68|
|Prehospitalpulse oximetry (N, % Yes)||193 (97%)||171 (97%)||364 (97%)||0.945|
|Neurosurgical procedure (N, % Yes)||140 (66%)||137 (65%)||277 (66%)||0.89|
|EDH evacuation (N, % Yes)||23 (11%)||18 (9%)||41 (10%)||0.553|
|SDH evacuation (N, % Yes)||44 (22%)||41 (20%)||85 (20%)||0.846|
|Parenchymal hemorrhage evacuation (N, % Yes)||4 (2%)||2 (1%)||6 (1%)||0.698|
|Days of ICP monitoring (median, IQR)|
|All patients||1 (0-8)||3 (0-8.75)||2 (0-8)||0.173|
|Survivors||1 (0-8)||3.5 (0-10)||3 (0-9)||0.199|
|Dead||1 (0-5.5)||1 (0-5.3)||1 (0-5.5)||0.867|
|Days of ventilation (median, IQR)|
|All patients||5 (2-14)||5 (1-15)||5 (1-14)||0.282|
|Survivors||7 (1-14)||7 (0-16)||7 (1-16)||0.412|
|Dead||4.5 (2-10.5)||3 (2-7)||4 (2-9)||0.388|
|Days at ICU (median, IQR)|
|All patients||10 (4-20.5)||10 (2.5-21.3)||10 (3-21.2)||0.686|
|Survivors||13 (5.5-24)||13.5 (4-22.9)||13 (5-23)||0.43|
|Dead||4.5 (2-10.4)||2.4 (0.9-8.9)||4 (2-10)||0.118|
|Days at hospital (median, IQR)|
|All patients||18 (6-33.6)||18.5 (7-33.4)||18.4 (6.6-34)||0.412|
|Survivors||23 (13.8-41.5)||21.2 (14-39.4)||22.2 (14-42)||0.577|
|Dead||5 (2-12)||3.2 (1.3-8.9)||4 (2-12)||0.32|
|ICU mortality (N, %)||54 (26%)||38 (18%)||92 (22%)||0.068|
|Hospital mortality (N, %)||66 (31%)||42 (20%)||108 (26%)||0.01|
|Six months unfavorable outcome (N, %)||96 (46%)||82 (39%)||178 (42%)||0.2|
EDH: Epidural Hematoma; SDH: Subdural Hematoma; ICP: Intracranial Pressure; ICU: Intensive Care Unit; IQR: Interquartile Range; ICU: Intensive Care Unit
Table 2: Treatment factors and outcomes.
|ICU outcome||Hospital outcome||Long Term outcome (Favorable=1)|
|OR (CI95%)||P-value||OR (CI95%)||P-value||OR (CI95%)||P-value|
|Rotem||2.1 (1.2-3.5)||<0.01||2.5 (1.5-4.1)||<0.001||1.6 (1.02-2.4)||0.039|
|(Used vs. No)|
|ISS||0.95 (0.94-0.96)||<0.001||0.97 (0.95-0.98)||<0.001||0.97 (0.95-0.99)||<0.001|
|GCS||1.2 (1.07-1.32)||<0.01||1.2 (1.1-1.3)||<0.001||1.1 (1.03-1.19)||<0.001|
|Age||0.97 (0.96-0.98)||<0.001||0.97 (0.96-0.98)||<0.001||0.97 (0.96-0.98)||<0.001|
GCS: Glasgow Coma Scale; ISS: Injury Severity Score; OR: Odds Ratio; CI: Confidence Interval
Table 3: Multivariate analysis.
To the best of our knowledge this study is the largest study that investigated the association between use of TEM and outcomes after TBI. This study shows that the use of TEM during the first 2 h after hospital admission (i.e., during treatment in the trauma room and the operating theatre) was associated with better outcomes. This was most probably due to interventions based on TEM findings, e.g., use of fibrinogen, of platelets, of prothrombin complex concentrates, and/or of anti-fibrinolytic medication . Unfortunately, we do not have any information which coagulation-related treatment the patients actually received because these data were not collected in the two observational studies from which we selected our cases. This is a major limitation of this study. The use of TEM together with the “platelet-mapping” technique has become a standard in large German as well as Austrian trauma centers, and management of coagulation has become a key element of the treatment of major trauma also elsewhere [19-21]. The use of TEM provides fast point-of-care information about significant post-traumatic coagulation problems. Using only 300 microliters of whole blood the technique measures the viscoelastic properties of a blood clot and provides the information on the speed of initiation of clotting, kinetics of the growth of the clot, strength of the clot and time to breakdown of the clot.
This information is provided numerically as well as graphically, and is therefore easy to read. The two most important tests are done using either activated thromboplastin (“extem”) or cytochalasin D (to inhibit the action of platelets on the growing clot; “fibtem”). Initial test results are available 5 min after the start of the test, full test results are available after 20 min. If the initial test results show typical patterns (e.g., only small amplitude in “fibtem”) treatment may be initiated within a few minutes after start of the test. A typical example is given in a case report by Schochl et al. . To get continuous information a new test could be started every 5-10 min this means that two TEM devices are used in many centers. A third test (“aptem”) uses aprotinin to inhibit fibrinolysis but is otherwise similar to “extem”. Fibrinolysis is present if clot strength is normal on “aptem” and low on “extem”. The most frequent finding after TBI is small amplitude on “fibtem” indicating decreased fibrinogen levels and/or impaired fibrin polymerization. Thus, administration of fibrinogen is usually the first-line treatment. If the maximum amplitude on “extem” does not increase after fibrinogen administration the use of platelet concentrates is indicated. Prolonged clotting time on “extem” warrants the use of prothrombin complex concentrates. In cases with increased fibrinolysis the use of tranexamic acid or other anti-fibrinolytic medications is necessary. This “goal-directed” treatment of coagulopathy after trauma avoids the need for large doses of fresh frozen plasma, and has been shown to improve outcomes after trauma . TEM findings have also been used to identify patients with poor prognosis after TBI as well as after trauma. In both of these retrospective studies poor clot strength and hypocoagulability were associated with worse outcomes. In the TBI study  8/78 patients (10%) were diagnosed by TEM to have hypocoagulability; this was confirmed by standard tests of coagulation in only 2/8 patients (25%). In the general trauma study  patients with poor clot strength had a significantly higher ISS than patients with normal clot strength (27 vs. 19; p=0.006).
In conclusion, our study showed that the early use of TEM was associated with improved outcomes after TBI. Unfortunately, due to the retrospective nature of our study we were unable to provide information on the coagulation-related treatment. A large prospective study should be done to investigate and define the possible benefits of “goal-directed” management of coagulation after severe TBI.
We are very grateful to the investigators from the participating centers who enrolled patients and collected data: H. Artmann MD (Schwarzach), N. Bauer MD (Linz UKH), F. Botha MD (Linz WJ), F. Chmeliczek MD (Salzburg LKA), G. Clarici MD (Graz Uni), D. Csomor MD (Wr. Neustadt), R. Folie MD (Feldkirch), R. Germann MD, PhD (Feldkirch), F. Gruber MD (Linz AKH), H-D. Gulle MD (Klagenfurt), T. Haidacher MD (Graz UKH), G. Herzer MD (Wr. Neustadt), P. Hohenauer MD (Salzburg LKA), A. Hüblauer MD (Horn), J. Lanner MD (Salzburg UKH), V. Lorenz MD (Wien UKH XII), C. Mirth MD (St. Pölten), W. Mitterndorfer MD (Linz AKH), W. Moser MD (Klagenfurt), H. Schmied MD (Amstetten), K-H Stadlbauer MD, PhD (Innsbruck), H. Steltzer MD, PhD (Wien UKH XII), Ernst Trampitsch MD (Klagenfurt), A. Waltensdorfer MD (Graz Uni), A. Zechner MD (Klagenfurt). We are also grateful to researchers from INRO: Ingrid Wilbacher PhD collected data during the first project; Ivan Janciak PhD developed and managed the databases used for both projects.
Alexandra Brazinova: project manager for the second project, entered the data collected by the local investigators, analyzed data quality, and wrote part of the paper
Walter Mauritz: developed both observational projects, analyzed data, and wrote part of the paper
The data used for this study was collected for a project funded by the Austrian Worker’s Compensation Board (AUVA; FK 33/2003) and by the “Jubilee Fund” of the Austrian National Bank (Project No. 8987), and for a project funded by the Ministry of Health (Contract Oct. 15, 2008) and the AUVA (FK 11/2008, FK 11/2010, FK 09/12). INRO is supported by an annual grant from Mrs. Ala Auersperg-Isham and Mr. Ralph Isham, and by small donations from various sources.
The authors do not have any conflicts of interest.
This study has not been presented anywhere.