Thromboelastography

Excerpt

Maintaining blood in a liquid state is critical for homeostasis. It allows blood to supply adequate oxygen and nutrients to tissues while also eliminating carbon dioxide and other waste products. On the other hand, the ability of blood to convert from a liquid to a solid state, in other words, to coagulate, underlies the mechanism that protects the body from life-threatening exsanguination. This process of thrombosis is normally a localized event at the site of vascular injury while the rest of the circulating blood remains in a liquid state. Thrombosis is a dynamic process that includes associated thrombolysis to maintain or restore blood flow through vessels once an injury has been sealed. These unique properties of blood are largely determined by a complex and active balance between pro-coagulation factors, anticoagulants, and fibrinolysis. Two major pathologic conditions are commonly associated with disequilibrium of this intricate system: bleeding and vessel thrombosis.

Major bleeding is a serious medical complication that may be caused by external trauma, surgery, invasive procedures, or an underlying medical condition such as aneurysm rupture or peptic ulcer disease. According to the World Health Organization (WHO), injuries are responsible for 5.8 million deaths per year worldwide, with the associated bleeding responsible for about 30% to 40% of these deaths. Several congenital disorders associated with a coagulation factor deficiency, such as Von Willebrand disease, hemophilia A or B, may cause significant bleeding even with minor injuries. Also, prescribed anticoagulants and antiplatelet agents may create a coagulopathic state that may lead to excessive bleeding either associated with trauma or medical procedures. Finally, major acute blood loss can lead to coagulopathy due to a loss of coagulation factors. Predictably, trauma-related coagulopathy has been associated with significantly higher mortality. Patients with ongoing or expected major bleeding would benefit from an accurate assessment of the functional state of the hemostatic system to provide optimal care, providing cost-effective replacement of only the needed blood components.

Venous thromboembolism (VTE) is another common and serious condition that is associated with abnormal blood coagulation. In these cases, systemic hypercoagulability shifts the body’s homeostatic mechanisms toward a pro-thrombotic state. In particular patients, however, a definitive cause for the VTE may be unclear. Routine coagulation testing has not been shown to predict such events, and in many cases, even a detailed hypercoagulability investigation fails to identify an underlying disorder. Many people take anticoagulants and antiplatelet agents regularly, which impacts the accuracy of the results of many laboratory coagulation studies. An accurate and cost-efficient method of monitoring antithrombotic activity would be helpful to maintain an acceptable risk/benefit ratio in such patients. Inadequate anticoagulation or antiplatelet therapy can lead to devastating thromboembolic conditions.

Several commonly used blood tests assess blood coagulation. These tests include prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT), platelet count, fibrinogen concentration, D-dimer level, activated clotting time, and whole blood bleeding time (BT). These tests are usually used for the clinical diagnosis of coagulopathy and a possible prothrombotic state, to monitor anticoagulation therapy, and to assist in treating bleeding episodes. More specific factor analyses, such as Factor V, proteins C and S, anti-thrombin III, anticardiolipin antibodies, and prothrombin gene mutation, are useful but not as readily available in emergency clinical situations. Despite being very effective for specific clinical needs, such as anticoagulation monitoring, the first group of usual diagnostic tests has limitations. Their main disadvantage in circumstances of acute major bleeding is the long turnaround time. Furthermore, they do not provide a complete picture of hemostasis due to their inability to assess some coagulation factors (such as Factor XIII), platelet function, and the activity of the fibrinolytic system. Platelet concentration, easily measured as part of a complete blood count, does not necessarily reflect their function, especially in the presence of elements known to affect platelet reactivity, such as non-steroidal anti-inflammatory drugs, antiplatelet agents, uremia, malignancy, or alcohol intake. Bleeding time has a low sensitivity and high inconsistency in detecting platelet disorders. Delayed or inadequate diagnosis of coagulopathy in a bleeding patient may lead to an excessive and improperly balanced transfusion of scarce blood components with increased morbidity, treatment costs, and mortality.

Thromboelastography (TEG) is a promising diagnostic modality that offers several advantages compared to the other tests that have been mentioned above. TEG was developed and first described by Dr. Hellmut Hartert at the University of Heidelberg (Germany) in 1948. The first reported clinical application of the test occurred during the Vietnam War in an attempt to guide transfusions of blood components in injured soldiers. In the 1980s, TEG was found to be beneficial in liver transplant patients, and in the 1990s, it was demonstrated to be useful in cardiac surgery. Since then, TEG has evolved into a more commonly used test as more evidence for its clinical efficacy has been attained. A brief search in PubMed using keywords “thromboelastography” and “thromboelastometry” results in about 6000 publications. This article will describe the general principles of TEG, methodology, normal values, along with the current evidence and clinical applications, as well as limitations and future research directions.