Journal of Neuroscience Nursing:
Utility of Thromboelastography in Traumatic Brain Injury and the Neuroscience Intensive Care Unit
Figueroa, Stephen A.; Merriman-Noesges, Karen
Questions or comments about this article may be directed to Stephen A. Figueroa, MD, at firstname.lastname@example.org. He is an Assistant Professor of Neurology and Neurotherapeutics at University of Texas Southwestern, Dallas, TX.
Karen Merriman-Noesges, MSN RN APRN ACPN-BC, is a Nurse Practioner at University of Texas Southwestern, Dallas, TX.
The authors declare no conflicts of interest.
Hemorrhage in trauma patients, despite damage control surgery, is responsible for up to 40% of trauma-related deaths and increased morbidity in traumatic brain injury (TBI). Current theory proposes that the initial tissue injury, hypoperfusion, accelerated fibrinolysis, and inflammatory mediated responses are the most likely culprits in trauma-induced coagulopathy. Interactions between thrombin, fibrinogen, platelets, protein clotting factors, calcium ions, inflammatory mediators, and endothelium contribute to systemic coagulopathy present in the trauma population. In addition, coagulopathy in the setting of hypothermia, acidosis, clotting factor depletion, and dilutional effects of trauma resuscitation compromise the body’s ability to achieve homeostasis and place the trauma patient at significant risk for thromboembolic events (Gonzalez, Pieracci, Moore, & Kashuk, 2010). Coagulopathy is associated with an estimated fivefold increase in mortality, and 25% of trauma patients are coagulopathic on admission (Toker, Hak, & Morgan, 2011). Coagulopathy is an independent predictor of morbidity and mortality in isolated TBI (Davis et al., 2013). Over the years, coagulopathy in TBI has been consistently identified by derangements in the standard coagulation studies of prothrombin time, international normalized ratio, activated partial thromboplastin time, and platelet counts, but these tests were not developed to adequately assess the coagulopathy (Davis et al., 2013).
Thromboelastography (TEG) is more precise in identifying the exact derangements of hemostasis compared to conventional methods, especially when they fail to detect the coagulopathy. TEG is superior to prothrombin time, international normalized ratio, activated partial thromboplastin time, and other conventional coagulation laboratory tests in identifying coagulopathy and thrombin activity, and TEG has the ability to differentiate between enzymatic and platelet coagulopathy (Gonzalez, Kashuk, Moore, & Silliman, 2010). It provides information on clot initiation, clot growth, final clot strength, and presence of fibrinolytic clot breakdown, giving a global evaluation of all phases of the coagulation cascade (Schochl et al., 2011).
What Is TEG?
First described in 1948 by Hartert, TEG initially was developed to evaluate clotting factor deficiencies and then became a valid tool used in the assessment of anticoagulant effects, thrombocytopenia, and fibrinolysis. Initial clinical uses of TEG included liver transplant to evaluate fibrinolysis, cardiovascular surgery to monitor intraoperative heparin effect during cardiopulmonary bypass, and as a predictive tool for postoperative bleeding (Despotis, Joist, & Goodnough, 1997; Shore-Lesserson et al., 1999). TEG gained favor in general surgery for the ability to differentiate coagulopathy from surgical bleeding. Today, the use of TEG has broadened to emergency medicine, trauma, and critical care medicine (Gonzalez, Pieracci, et al., 2010; Kashuk et al., 2010). TEG’s superiority lies in its function as a rapid, global assessment of hemostatic function, taking into account the clotting cascade and platelet function in whole blood. It is the only test that can provide information on the balance of thrombosis and fibrinolysis and how these elements interact (Gonzalez, Pieracci, et al., 2010).
There are several parameters of TEG, and each coagulation derangement, including normal function, produce different but specific viscoelastic patterns (see Table 1). These viscoelastic TEG patterns identify specific factor deficiencies or inhibition due to anticoagulant medications. Decreased clotting and clot formation time as well as increased fibrinolysis also have a unique TEG tracing, which correlates with the specific hypocoagulable or hypercoagulable state. Platelet mapping assesses for degree or percentage of platelet inhibition, frequently caused by antiplatelet medications such as clopidogrel, aspirin, and dipyridamole or deriving from nonpharmacological platelet dysfunction (see Figure 1).
Primary brain injury occurs at the time of trauma. The damage that results includes a combination of focal contusions and hematomas, as well as shearing of white matter tracts (diffuse axonal injury) along with cerebral edema and swelling, which releases tissue factor (TF) into the circulation. Secondary brain injury results from the ensuing inflammatory cascade, resulting in ischemia and cortical depression. Thrombocytopenia and coagulopathy can worsen primary brain injuries, which can negatively affect patient outcomes (Murray et al., 2007). As the severity of the injury increases, there is increased risk for development of hemorrhagic progression or new hemorrhage (Carrick, Tyroch, Youens, & Handley, 2005; Zehtabchi et al., 2008). However, bleeding can still occur even when platelet count and conventional coagulation studies are within normal ranges. Bleeding may not be the result of hemodilution and consumption but rather may result from platelet dysfunction (Nekludov, Bellander, Blomback, & Wallen, 2007). TEG with platelet mapping can determine the degree of platelet inhibition due to either quantitative or qualitative dysfunction (Sillesen et al., 2013). Platelet dysfunction also can be an early marker of trauma-induced coagulopathy, which correlates with mortality (Davis et al., 2013).
Hypocoagulable and Hypercoagulable States
Coagulopathy after TBI is linked to injury-mediated release of TF, activating the extrinsic pathway of coagulation. TF exists at high levels in the brain and is believed to set in motion early coagulopathy following head trauma (Toker et al., 2011).
Hypercoagulation in TBI is believed to start immediately after injury, exists for a very short period of time, and then transitions into a hypocoagulable state (Brohi et al., 2008). Patients who survive the acute phase of trauma will evolve back to a hypercoagulable state rapidly. The exact timing of this transition, however, is poorly understood (Schreiber, Differding, Thorborg, Mayberry, & Mullins, 2005). Dysfunction within Virchow’s triad, which includes hypercoagulability, endothelial injury, and venous stasis, leads to high risk for thromboembolic events in patients with trauma and head injury (Ruiz, Hill, & Berry, 1991). Platelet activation also is identified as a contributing factor in the development and proliferation of venous thrombi (Furie & Furie, 2008).
Hypocoagulation stems from tissue injury, hypoperfusion, accelerated fibrinolysis, and increased inflammatory cascades. This theory is known as the cell-based model of hemostasis. The cell-based model of hemostasis emphasizes the role of TF as responsible for inducing coagulation and is influenced by protein and platelet receptors, endothelial cells, and inflammatory cytokines (Hoffman & Monroe, 2001). Activation of the immune complement system is another component in the development of a coagulopathic process (Gonzalez, Pieracci, et al., 2010).
Functional fibrinogen, along with platelets, is necessary for clot formation and stability. The role of platelets is to maintain hemostasis by forming thrombi when vessel endothelium is damaged. Platelets also require regulation to inhibit thrombus formation when no endothelial damage is present. Platelets are activated by collagen, Von Willebrand factor, and thrombin. Tissue injury, hypoperfusion, and immune system activation lead to impaired thrombin production and increased fibrinolysis (Harr et al., 2013). The result is impaired platelet function, decreased conversion of fibrin to fibrinogen, and poor hemostatic plug formation (Jennings, 2009). Thrombin directly activates factors V, VIII, and XIII. It is also responsible for activating the factor inhibitor, protein C. The coagulation cascade sustains a prothrombotic state when not actively being modulated by the anticoagulant pathways as a result of activation of TF pathways.
In addition to TEG’s unique coagulation assessment ability, TEG is known to predict thrombotic events in surgical patients (McCrath, Cerboni, Frumento, Hirsh, & Bennett-Guerrero, 2005). The traditional risk stratification assessments do not include information on coagulation status and hypercoagulable states as risk factors for perioperative morbidity and mortality. Kashuk et al. (2009) used rapid TEG to assess the coagulation status of critically ill surgical patients. A significant association was identified between hypercoagulable states measured by rapid TEG and subsequent thrombotic complications, despite chemoprophylaxis.
In a review of venous thromboembolism (VTE) in neurology and neurosurgical patients, Hamilton, Hull, and Pineo (1994) reviewed 15 studies dating from 1960 documenting the incidence of deep vein thrombosis, pulmonary embolus, and associated mortality percentage. Ettinger (1970) described coagulation abnormalities occurring in patients with subarachnoid hemorrhage and the use of TEG profiles to study coagulopathy in cerebral infarction. Neurosurgical literature has cited acute intracerebral hemorrhage, unstable aneurysm after subarachnoid hemorrhage, and intramedullary spinal cord hemorrhage as absolute contraindication for anticoagulant therapy for treatment of VTE. Patients with TBI and postsurgical craniotomy patients are candidates for anticoagulation therapy, but there is much debate over wait time before treatment can be initiated safely (Hammond & Meighen, 1998). Given the increased morbidity and mortality associated with secondary intracranial hemorrhage, anticoagulant therapy for patients with head injury needs to be a balance between effective prevention of VTE and low risk of secondary bleeding complications. Studies using TEG-guided chemoprophylaxis in patients with head injury are an appropriate and necessary step to improving clinical care and outcomes.
Nontraumatic Acute Brain Injury
Studies are limited, but some work has been published about subarachnoid hemorrhage, ischemic stroke, intravenous thrombolytic therapy, increased intracranial pressure, and hyperosmolar therapies. Windelov, Welling, Ostrowski, and Johansson (2011) found and association between hypocoagulable TEG profile and worse outcomes in patients with isolated primary intracranial hemorrhage and/or isolated TBI. TEG has been used to assess coagulopathy in brain tumor patients by detecting specific clot characteristics that revealed a hypercoagulability during brain tumor surgery (Goh, Tsoi, Feng, Wickham, & Poon, 1997). Alterations to the hemostatic system have been studied in experimental rat models of aneurysmal subarachnoid hemorrhage using TEG, and an immediate hypercoagulable state is present immediately after experimental aneurysmal subarachnoid hemorrhage, indicated by a higher maximum amplitude and shorter R (reaction) time (Larsen, Hansen-Schwartz, Nielsen, & Astrup, 2010). The relationship to increased intracranial pressure and the development of coagulopathy has been studied in animal models. Increased intracranial pressure was associated with pronounced activation of the coagulation system and is most likely associated with TF release (Barklin, Tonnesen, Ingerslev, Sorensen, & Fenger-Eriksen, 2009). Mannitol and hypertonic saline both interfere with various aspects of coagulation. Mannitol 15% is known to reduce clot strength, and when combined with other agents, such as plasma expanders, it can disrupt fibrin formation. In concentrations of 3% to 7.5%, hypertonic saline disrupts both fibrin formation and platelet function (Luostarinen, Niiya, Schramko, Rosenberg, & Niemi, 2011). TEG is now being studied in acute ischemic stroke. Elliott et al. (2012) evaluated TEG profiles before and after administration of intravenous tissue plasminogen activator (tPA) in the hopes of identifying clot subtype and possibly predicting response to tissue plasminogen activator. A future study is currently ongoing.
TEG is an established point-of-care test used to identify coagulopathy in a variety of patient populations. Regardless of the mechanism of injury, the neurologically injured patient remains at a higher risk for complications of VTE. The concern for secondary hemorrhage related to anticoagulant therapy is justified, but perhaps this risk can be better stratified from low to high using viscoelastic tests. TEG-guided protocols have been initiated in multiple institutions to identify and treat existing coagulopathies, reduce blood consumption, and ensure transfusion of appropriate blood products. TEG also has been shown to have predictive abilities for VTE and myocardial infarction. TEG is more precise in identifying derangements of hemostasis and coagulopathy. The future forecasts a transition from traditional coagulation testing to TEG profiles as the standard of care.
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