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Thromboelastography-Guided Transfusion

Therapy in the Trauma Patient
Charice Brazzel, CRNA, DNP
This article presents thromboelastography (TEG) as
an important assay to incorporate into anesthesia
practice for development of evidence-based therapy of trauma patients receiving blood transfusions.
The leading cause of death worldwide results from
trauma. Hemorrhage is responsible for 30% to 40%
of trauma mortality and accounts for almost 50% of
the deaths occurring in the initial 24 hours following
the traumatic incident. On admission, 25% to 35% of
trauma patients present with coagulopathy, which is
associated with a sevenfold increase in morbidity and
mortality. The literature supports that routine plasmabased routine coagulation tests, such as prothrombin
time, activated partial thromboplastin time, and international normalized ratio, are inadequate for monitor-

T

he trauma patient presents special conditions and problems for anesthesia providers.
The trauma triad of death is a medical term
that is often used to describe the conditions
of hypothermia, acidosis, and coagulopathy.1
This triad is seen in patients who have severe traumatic
injuries and is the cause of a major rise in the mortality
rate because of continual microvascular bleeding.2 The
leading cause of death worldwide results from trauma,
with hemorrhage being responsible for 30% to 40% of
trauma mortality and accounting for almost 50% of the
deaths occurring in the initial 24 hours following the
traumatic incident.3 On admission, 25% to 35% of trauma
patients present with coagulopathy, which is associated
with a sevenfold increase in morbidity and mortality.4
There is emerging consensus that routine plasma-based
tests (RCoT), such as prothrombin time (PT), activated
partial thromboplastin time (APTT), and international
normalized ratio (INR), may be inadequate for monitoring coagulopathy and guiding transfusion therapy in
trauma patients.3 A correct diagnosis is critical for patient
survival. Applying the thromboelastography (TEG) assay
to transfusion therapy for the trauma patient can help
guide the anesthesia provider to correctly diagnose and
properly treat the hemorrhaging patient. Closing the
gap between coagulopathic hemorrhage and death will
require a change in current clinical practice to modify and
update transfusion regimens.
The purpose of this article is multifaceted. The author
outlines the importance of addressing coagulopathic

www.aana.com/aanajournalonline

ing coagulopathy and guided transfusion therapy in
trauma patients.
A potential solution is incorporating the use of the
TEG assay into the care of trauma patients to render
evidence-based therapy for patients requiring massive
blood transfusions. Analysis with TEG provides a complete picture of hemostasis, which is far superior to
isolated, static conventional tests. The result is a fast,
well-designed, and precise diagnosis enabling more
cost-effective treatment, improved clinical outcome,
accurate use of blood products, and pharmaceutical
therapies at the point of care.
Keywords: Coagulopathy,
transfusion therapy, trauma.

thromboelastography,

conditions that can be experienced in trauma patients
and relates contributing factors to the development of
this derangement. A comprehensive history and review
of the literature are presented to demonstrate a thorough
assessment of the problem relating to coagulopathy. An
explanation is provided to the reader why RCoT may
be inadequate to guide transfusion therapy in trauma
anesthesia and why TEG may serve as a more preferable
diagnostic assay. The pathways of coagulation are discussed, and finally, the author offers recommendations
for future practice.

History and Review of Literature
Evidence from the relevant literature suggests it is important to address coagulopathy in trauma patients.
Results of a study between cohorts presenting with
similar injury severity scores determined that the patient
cohort presenting with coagulopathy experienced 2 to
3 times greater mortality rate.5 The prevention of coagulopathy is superior to treatment, yet most protocols
are designed to treat preexisting and/or ongoing coagulopathy.6 Uncontrolled coagulopathic hemorrhage is now
seen as the major cause of preventable death in trauma
patients.7 There are 3 phases of hemorrhagic shock due
to coagulopathy. These phases are compensated, uncompensated but reversible, and irreversible hemorrhagic
shock. Once the irreversible hemorrhagic shock phase
has been entered, blood pressure, tissue oxygenation,
and perfusion do not improve with either fluid replacement therapy or the use of inotropic agents.8 The goal of

AANA Journal

April 2013

Vol. 81, No. 2

127

and obstetrics. and fibrinolysis (Figure 2). reduction of enzyme activity.10 Thromboelastography can enable the anesthetists to minimize hemodilution and possibly prevent exacerbation of coagulopathies by transfusing the correct blood product when the patient needs it. By the time that type-specific fresh frozen plasma. These products may further dilute coagulation factors contributing to a negative spiral effect of dilutional coagulopathy. these plasma-based tests communicate only the small amount of thrombin formed during the initial phases of coagulation and have little predictive value (≤ 50%) with respect to hemorrhage. and uncrossmatched packed red blood cells (RBC) because of ease of availability. Hess et al5 asserted that several factors contribute to the development of coagulopathy: blood loss.12 A new understanding of the classic coagulation cascade was put forth in 1994 by the introduction of a cell-based model. These values expose the precise mechanism contributing to the coagulopathy. 2 Figure 1. 81. liver transplantation. Thromboelastograph Components α angle R MA K Figure 2. volume resuscitation starts with a combination of crystalloids. they generally fail to correct the coagulopathy because of hemodilution. and cryoprecipitate are added to the regimen. A small sample of whole blood (0. and interest has renewed in viscoelastic assay studies to guide transfusion therapy in trauma patients.aana. hypothermic platelet dysfunction. This sluggish flow mimics the venous circulation and activates the coagulation process. and INR results are consistent with increased mortality in the trauma patient.36 mL) is placed into a cup heated to 37˚C.13 The cell-based model emphasizes the importance of tissue factor as the initiator of the coagulation cascade and the pivotal role of platelets for intact hemostasis. and unopposed fibrinolysis. APTT. and fibrin begins to form between the torsion wire and the wall of the cup. Thromboelastograph Tracing The TEG assay is a relatively simple process. and the MA (width of tracing representing clot strength). platelets. Thromboelastography is a real-time viscoelastic assay that measures the strength of fibrin-platelet bonds in whole blood. The cup is gently rotated back and forth constantly. acidosis-induced reduction in coagulation factor activity.com/aanajournalonline . Historically. This new understanding explains the poor correlation between RCoT and clinical bleeding and provides a more accurate picture of why use of these laboratory studies is insufficient in trauma resuscitation.3. TEG analysis has been used extensively in the disciplines of cardiovascular surgery. The result of this process is a functional hemostatic plug.13 Correct detection of coagulopathy is crucial for survival. Uncrossmatched packed RBC are readily available but are generally used only in cases of dire emergency. as depicted www. A stationary pin attached to a torsion wire is inserted into the sample cup. through an arc (cycle time. consumption of platelets. 6/ min). K value (fibrin kinetics or speed of clot formation).14 128 AANA Journal  April 2013  Vol.11 These assay tests were developed more than 50 years ago for treatment of patients with hemophilia and have never been validated for the prediction of uncontrolled hemorrhage in trauma patients. The recognition of coagulopathy at the time of admission is crucial.9 ABO typing of blood and thawing of component replacement factors requires time during the initial phase of the resuscitation. platelet function. This fibrin-platelet binding links the cup and pin together (Figure 1). Customarily. α angle (fibrin cross-linking).resuscitative care is to delay or prevent the transition to irreversible hemorrhagic shock. hemodilution by physiologic vascular refill. The speed and strength of clot formation are converted by a mechanical-electrical transducer to an electrical signal that is computer analyzed. There has been growing consensus that RCoT are ill suited for monitoring coagulopathy and guiding transfusion therapy in hemorrhaging patients. No. Even though abnormal PT. at a set speed. colloids. There are 4 main values of interest expressed in this assay: the R value (start of clot or fibrin formation). These data are converted to a numeric value and graphic representation of the plasmatic coagulation system.

and/or hemodilution.17 Information on these important feedback loops are lost because only isolated pieces of the pathway are examined in RCoT because of whole blood is not being analyzed. Therefore. and a high value may indicate hypercoagulability for which the patient may benefit from anticoagulant therapy. and treatment with an anticoagulant of choice may prove beneficial. 45° to 55°) depicts the speed at which the clot strengthens.Cause Treatment R value K and α value MA Lack of surgical hemostasis Sutures Normal Normal Normal Hemodilution No treatment necessary High Normal Normal Factor deficiency FFP High Low or normal Low or normal Fibrinogen deficiency Cryoprecipitate Normal Low Low or normal Platelets low or dysfunctional Platelets Normal Normal Low Primary fibrinolysis Antifibrinolytics. The factors represented are XII. The prolongation of this value can represent a deficiency in coagulation factors. XI. and Z. TXA. K value. it signals the beginning of the final common pathway. Thrombin cleaves fibrinogen to fibrin monomers. in Table 1.16 Confounding the problem with RCoT is the fact that platelets are responsible for approximately 80% of total clot strength.aana. only www. Factor VIIa will subsequently bind with tissue thromboplastin to convert factor X to Xa. which AANA Journal  April 2013  Vol. effects of endogenous heparin released in trauma. and an anticoagulant of choice may be clinically indicated.com/aanajournalonline 2 coagulation proteins are represented in the extrinsic pathway. An MA result greater than 75 mm is evidence of a prothrombotic state. TXA. decreased platelet function. 50-60 mm). Thrombin will activate factor V to factor Va and factor VIII to factor VIIIa and will serve as a positive feedback loop.15 Transfusing platelet pools in patients who present a decreased MA may improve hemostatic conditions. The qualitative analysis that TEG provides can facilitate administration of the right blood product or anticoagulant. The K value (normal. Tissue factor is exposed from the injured endothelium and combines with factor VII to produce factor VIIa. tranexamic acid. Platelets are an important variable in the hemostatic process and are immediately lost during the centrifuge process. A decreased value can result from hypofibrinogenemia. S. This condition omits information on approximately 97% of the hemostatic process. The PT and INR depict the extrinsic pathway of the coagulation cascade. the MA. fresh frozen plasma. This positive feedback mechanism greatly increases the production of thrombin. C. Formation of fibrin polymers serves as the first mechanical evidence of a clot. IX. or maximum amplitude (normal. 3-6 minutes) and α angle (normal. 2 129 . start of clot or fibrin formation. or platelet dysfunction. in correct amounts. disseminated intravascular coagulation. or less than 3% of the overall clot strength. the plasma and the contribution of platelets in their role to clot strength are gone. fibrin kinetics or speed of clot formation. Thrombin plays perhaps one of the most underappreciated roles in the coagulation cascade. Although there is twice the amount of information. at just the right time. R value. which results in the cross-linking of fibrin strands. A low value may indicate the need for fibrinogen administration. Analysis of the intrinsic pathway offers double the amount of information about the coagulation pathway compared with the extrinsic pathway. FFP.11 Discussion • Coagulation Pathways. aprotinin Normal Normal Low Fibrinolysis (DIC) Stage 1: Hypercoagulability with fibrinolysis Treat DIC Low High High Fibrinolysis (DIC) Stage 2: Hypocoagulability after consumption Treat DIC High Low Low Table 1. to form fibrin polymers. a shortening in the R value (less than 3 minutes) would indicate a state of hypercoagulability. Last. less than 10% of the overall clot strength is represented in this APTT assay. When factor X is activated. The conversion of prothrombin to thrombin is where the serious affair of the hemostatic process truly begins. and VIII and 3 natural anticoagulant proteins. Conversely. 7. It is at this point where all RCoT assays stop analysis. Routine coagulation tests stop where fibrin strands begin to form.16 When the final common pathway is reached by either intrinsic or extrinsic mechanisms. The differential diagnosis can be deduced whether the dysfunction is a result of hemodilution. No. 81. Thromboelastography Values and Treatment Abbreviations: DIC. loss of coagulation proteins.5-15 minutes). factor X is activated and the conversion of prothrombin to thrombin results. The R value represents the reaction time for initial fibrin formation (normal. or quantity. MA. Thrombin will continue to activate factor XIII.15 The treatment with fresh frozen plasma or no treatment would depend on the clinical picture of the patient. When RCoT assays are analyzed. and this reveals less than 5% of overall thrombin produced. represents the overall maximum attainable clot strength. width of tracing representing clot strength.

The TEG assay produces a rapid. Each variable communicated by TEG assay expresses a unique component or relationship within the delicately balanced coagulation cascade process and benefits the practitioner by early detection of coagulopathic derangements. fresh frozen plasma. Small shifts in pH has a much greater effect on the coagulation process than small changes in temperature. however. RCoT. A recent study published by Edens et al36 suggested that there might be an independent relationship between the amount of fresh frozen plasma transfused and the development of early acute lung injury. the kinetics of initial fibrin clot formation and length of time to achieve maximum strength. TEG. Comparison Studies of Routine Coagulation Tests and Thromboelastography Abbreviations: FFP.25-27 This approach to trauma resuscitation has been widely studied in severely injured patients and has become a commonplace practice to minimize dilutional coagulopathy. This fundamental principle further explains why RCoT do not agree with actual clinical bleeding observed in vivo. platelets and cryoprecipitate is not only uneconomical.” Perkins et al34 reported improved 30-day survival rates associated with the increased use of platelets in massive transfusion. Hess et al5 posit that this practice is “dangerous. Randomized controlled trials comparing RCoT and viscoelastic assay are described in Table 2. Thrombin is the most potent platelet activator in the body and serves as the catalyst for the hemostatic process.20-22 The medical literature is replete with hazards associated with transfusion of allogeneic blood products.com/aanajournalonline .6.18 Thromboelastography evaluates the mechanical properties of the hemostatic process. The ongoing conflict in the United States Theater of Operations in the Middle East has produced retrospective data suggesting that whole blood is superior to component replacement therapy in the massively transfused trauma patient.aana. is that of platelet activation. FFP.10. These changes can exacerbate the conditions of the trauma patient because a normal serum pH does not consistently reflect the pH in hypoxic tissue. treating these patients indiscriminately with fresh frozen plasma. fresh frozen plasma. mortality rates have improved. red blood cells. The resulting strength of the fibrin clot formation determines how well the clot can prevent hemorrhage without permitting inappropriate thrombosis formation.28-33 However. a much larger amount of thrombin is necessary to produce a stable network of platelet-fibrin polymers. and platelets Table 2. and increased levels of supernatant potassium. 81. However. RBC. The optimal ratio of packed RBC to platelets is not clearly understood and warrants more investigation because although increased platelet ratios increase survival rates in massively transfused patients. Stored blood has lower levels of 2.12.3-diphosphoglycerate. 2 A landmark study conducted by Shore-Lesserson et al24 compared the effect of TEG-guided transfusion algorithm against routine transfusion therapy in patients undergoing complex cardiac surgery. and the final strength and stability of the fibrin clot. with the presence of bilateral pulmonary infiltrates. routine coagulation test. lower pH. • Benefits of TEG. thromboelastography.19 This translates to the potential for enormous savings in healthcare costs. they also are associated with multiple organ failure. decreasing the demand on our blood bank reserves and improving the quality of patient care.23 The TEG assay has been demonstrated to significantly decrease the requirement for perioperative allogeneic transfusion. Acute lung injury has a 33% rate of incidence among the critically injured trauma population.35 Acute lung injury is a syndrome of acute hypoxemic respiratory failure.14 130 AANA Journal  April 2013  Vol. evidence also suggests that www. The result produced a 75% reduction in the number of patients receiving fresh frozen plasma and more than a 50% reduction in the transfusion of platelets. No. low-cost method for differential diagnosis regarding the need for surgical reexploration in patients with continued microvascular oozing. of patients Major conclusions Shore-Lesserson et al24 (1999) Cardiac surgery 105 Patients who underwent TEG received less FFP and platelet transfusions postoperatively than did RCoT-treated patients Manikappa et al11 (2001) Cardiac surgery 150 TEG demonstrated greater accuracy than RCoT in predicting significant postoperative hemorrhage and significantly decreased the need for transfusion of RBC. Current studies advocate equal transfusion ratios of packed RBC. and platelets (1:1:1) to improve survival rates in trauma patients rather than early and substantial use of crystalloids and/or colloids. noncardiogenic in origin. Because of the current shifts in transfusion practice leaning toward infusion ratios of packed RBC to fresh frozen plasma approaching 1:1. Very small amounts of thrombin are required to cleave fibrinogen and activate platelets. including time to initial fibrin formation.Author (year) Type of surgery No.

38-40 A classic work by Ammar41 advances the use of TEG analysis for aiding early extubation. rendering a more cost-effective hospitalization course. An in-depth history and review of the literature has been presented to demonstrate a thorough assessment of the problem. and implement education and training among multiple hospital departments that would be affected by the practice change. 81. A preoperative platelet count provides information only on how many platelets are present and does not analyze functionality. Platelet mapping depicts whether a delay in surgery is necessary or. Further nursing research incorporating the TEG assay into the anesthesia preoperative screening phase can expand on the body of knowledge and possibly improve patient care. The intraoperative use of TEG analysis can identify the reason for the bleeding and guide therapy during the postoperative course. Thrombolytic drugs such as clopidogrel. which alter platelet adhesion and anchoring. Functional. which will facilitate earlier extubation and may decrease length of stay in the intensive care unit. Thromboelastography offers point-of-care testing. promote cooperative collaboration. Once the coagulation cascade has been activated. Currently. A paradigm shift in evidence-based practice is called for to embrace the TEG assay into patient care. The platelet system has 2 components: (1) activation and (2) aggregation. Strategies must be developed to assist the anesthetists to correctly interpret the results of TEG analysis. Patients receiving long-term thrombolytic therapy can be assessed preoperatively with precision and accuracy to determine the potential for perioperative hemorrhage. Pinpointing the dysfunction and formulating evidence-based therapy to address specific coagulopathies become a reality. • Practice Implications. however. Evidence-based transfusion therapy could offer mutual benefit to trauma patients and hospitals. rapid results in situations when decisions need to be made quickly without undue strain on blood bank resources. The return of platelet function can be followed with serial studies. Potential practice implications have been put forth to challenge anesthesia providers to adopt current evidencebased practice changes. TEG allows the practitioner to quantify and qualify 85% to 90% of this system. formulate therapeutic goals. and the need for platelet availability can be correctly anticipated.aana. Khan et al37 demonstrated that the development of acute lung injury was dose dependent on the actual numbers of fresh frozen plasma transfused. and develop appropriate transfusion guidelines. prasugrel. anesthetist. measurements are necessary to make evidence-based decisions on whether to proceed with surgical intervention. allowing the practitioner www. No.com/aanajournalonline to minimize complications and deliver specific treatment to the patient. The process of coagulation is dynamic.16 In a comparison of TEG with RCoT profiles. and abciximab act to prevent platelet aggregation in contrast to aspirin and nonsteroidal drugs. reduced medical costs without a decrease in patient care. Viscoelastic assays are currently endorsed by several international guidelines and textbooks concerning massive transfusion in trauma. Thromboelastography can provide anesthetists with information on which blood products would prove most efficacious to the hemorrhaging trauma patient and guide transfusion therapy in appropriate quantities. and hospitals. the question remains whether the platelets are functionally capable of aggregating to form a platelet plug. Incorporating the TEG assay into transfusion practice offers many distinct advantages. The TEG assay presents new challenges and practice implications to anesthesia providers. Prior studies have shown that the TEG assay allows for point-of-care testing that produces convenient. as well as decreased chance of future need for transfusions or additional surgery. Summary The purpose of this article has been to outline the importance of addressing coagulopathic conditions experienced in trauma patients and relate contributing factors to the development of coagulopathy. however. traditional RCoT results will provide at best a 51% predictive value for perioperative bleeding. hemorrhage and thrombotic issues are a shared concern across hospital specialties. which produces the advantage of convenient and rapid results when decisions need to be made. no published data exist quantifying how many hospitals use TEG analysis nationwide. A brief outline of the coagulation pathway has been presented along with a discussion detailing the advantages that the TEG assay can offer compared to RCoT. including earlier extubation. Early extubation is often prevented by excessive bleeding. not quantitative. 2 131 . may possibly proceed earlier than anticipated. This would be analogous to flipping a coin to determine results. This condition renders the patient hemodynamically unstable and may require surgical reexploration to determine the cause of the bleeding. and the patient implications related to this finding are unknown at this time. The potential positive results could promise better health outcomes for trauma patients. which can benefit the patient. Explanation has been given to the reader why RCoT assays may be inadequate to guide transfusion therapy in trauma anesthesia.this transfusion strategy may be associated with a higher incidence of acute lung injury. These evidence-based practice changes can serve to decrease mortality rates in the trauma population and possibly other medical disciplines. The TEG assay can be used for preoperative risk stratification based on individual hemostatic conditions. and less AANA Journal  April 2013  Vol. Accomplishing this objective will require the development of multidisciplinary teams to implement comprehensive strategies addressing policy and procedure development.

Cheng CA. et al. Miyao H. Hess JR. et al.95(2):112-119. Michalek JE.66(4 suppl):S77-S84. REFERENCES 1. Tetik S. Massive transfusion practices around the globe and suggestion for a common massive transfusion protocol. and the ugly. Repine TB. Trauma triad of death emergency. et al. American Society of Anesthesiologists Task Force on Perioperative Blood Transfusion and Adjuvant Therapies. Management of bleeding following major trauma: an updated European guideline. Hess JR. Tanaka KA. Bouillon B. and in some cases. Thromboelastography-based transfusion algorithm reduces blood product use after elective CABG: a prospective randomized study. Schreiber MA. Belsher J. Increased platelet: RBC ratios are associated with improved survival after massive transfusion.14(2):R52. Spinella PC. 2009. 18.S. Brohi K. Demetriades D. Thrombin formation. Can J Surg. Johansson PI. Manikappa S. Task Force for Advanced Bleeding Care in Trauma. Mann KG. Hunt JP. 2009. Perkins JG. Chest.65(3):527-534. 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The use of fresh whole blood in massive transfusion. 6. Edens JW. Factors that influence early extubation: bleeding. 2001. 2009. 2008. Spinella PC. 2009. 27. Platelet procoagulant complex assembly in a tissue factor-initiated system.