Although major surgeries such as liver transplanta-tion now use less blood than previously, more could be done to conserve blood products. There are risks and benefits associated with the transfusion of blood products. Overall, transfusion safety has im-proved dramatically over the past 20 years, but there is evidence to suggest that transfusion to various subgroups of surgical patients, including liver transplantation recipients, is associated with de-creased survival and increased number of periopera-tive complications. Thus, it is important to minimize the exposure of patients to transfused blood prod-ucts. The marked variability in blood use can partly be explained by differences in the characteristics of patient populations or differences in periopera-tive blood loss. The discrepancy in the amount of blood transfusion between similar procedures also points to a lack of objective standards that direct the use of blood transfusion. Not only is this a risk to the patient, but the unnecessary use of blood com-ponents increases health care costs and contributes to blood shortages. The consequences of unneces-sary blood transfusion make it important to ques-tion the rationale for giving some blood components and to refine the methods by which we determine if a transfusion is actually necessary. Optimal intra-operative coagulation management is probably one of the greatest challenges in this field.1
Blood coagulation monitoring offers the best objective evidence to guide hemostatic therapies, predict the risk of bleeding, reduce health care costs, and improve transfusion safety and patient outcome in liver transplantation and other surgical procedures.2 Recent published data have com-pared the use of two popular coagulation moni-tors: the Platelet Function Analyzer (PFA-100®) and the Thromboelastogram (TEG®) or modified TEG® (mTEG® or PlateletMappingTM).3−7 Nevertheless, con-troversies still exist with regard to using different reagents in the clinical setting.
The PFA-100® measures the time taken for a platelet plug to occlude an aperture in a mem-brane that is impregnated with collagen and epine-phrine or adenosine diphosphate (ADP). The time to occlude the aperture is called the closure time. Aspirin has been shown to increase the epinephrine closure time (C-EPI CT),8 while in some studies, clopidogrel has been shown to increase the ADP closure time (C-ADP CT).9−13 A recent review of the PFA-l00® concluded that it “provides a rapid, simple and reliable measure of platelet function”.14
The TEG® is a point-of-care coagulation monitor that measures some platelet aggregation defects in-cluding post-cardiopulmonary bypass-induced plate-let dysfunction related to glycoprotein IIb/IIIa receptors.15 However, conventional TEG®, because of the overwhelming presence of thrombin genera-tion, cannot often capture the platelet adhesion defects that occur with aspirin16−18 or demonstrate ADP receptor blockade with clopidogrel. Patients using clopidogrel who have definitive platelet inhi-bition as measured by aggregometry (and an 80% increase in the need for platelet transfusion after cardiac surgery) have been shown to have a normal maximum amplitude on conventional TEG®.18 How-ever, a recent modification of the TEG® (mTEG®) assay19 generates clot without thrombin generation using reptilase and factor XIIIa. The new TEG® assay overcomes this limitation. The addition of platelet agonists such as arachidonic acid or ADP facilitates measurement of platelet inhibition resulting from aspirin or clopidogrel, respectively. These new as-says show that mTEG® has good agreement with aggregometry.19 In 2006, Agarwal et al4 reconfirmed that there was good agreement between the results of aggregometry and mTEG® in patients taking clopidogrel.
In this issue of Acta Anaesthesiologica Taiwanica, Chang et al compare the sensitivity and specificity of the PFA-100® and TEG®.3 They use two agents (levobupivacaine and CGS21680) to induce plate-let dysfunction as detection target in an ex vivo experimental model. The starting platelet counts, platelet aggregation, closure time of PFA-100®, and the parameters of TEG® were examined. Their results showed that platelet aggregation was sup-pressed by levobupivacaine (10 μg/mL, 50 μg/mL, 200 μg/mL) and CGS21680 (100 nM, 500 nM, 1 μM) in a dose-dependent manner. Using the same doses, levobupivacaine and CGS21680 at the maximal dose of testing had no significant effect on each param-eter in the TEG® assay, but both levobupivacaine and CGS21680 showed significantly prolonged clo-sure time in the PFA-100® assay. The authors con-cluded that PFA-100® has higher sensitivity and specificity than TEG® for the detection of platelet dysfunction.3
However, a direct comparison of these tests is not simple. This is because the design principles, the reagents used, the testing profiles/functions, the scope of clinical application and data display of PFA-100® and TEG® are significantly different. Thus, it is difficult to do a one-sided comparison. The current clinical literature suggests that when using the PFA-100® analyzer to measure aspirin-mediated platelet inhibition, there are increased event rates in patients with a profile of aspirin re-sistance.6 This method has several limitations, however, including a poor correlation with other measures of platelet performance. In addition, this method relies on the von Willebrand factor level and its activity, and platelet count. The PFA-100® method also uses collagen and epinephrine as ago-nists, neither of which is specific for cyclooxygenase-1 activity, the target of aspirin. A major limitation of all the published studies of aspirin resistance is a lack of serial platelet function measurements, because the degree of aspirin resistance can fluc-tuate over time and can be affected by aspirin dose.6
The main issue of controversy raised from pre-vious studies was that TEG® could use five different reagents for detection: TEG-Kaolin, TEG-Heparinase, PlateletMapping™ (mTEG®), Rapid TEG® and func-tional fibrinogen test. After 2004, the mTEG® assay has been used to measure platelet function.4,6,20−23 In the mTEG® technique, the contribution of arachi-donic acid-induced platelet aggregation and ADP-induced aggregation to the overall tensile strength of a platelet-fibrin clot can be quantified and cor-related with turbidimetric aggregometry.24 The mTEG® assay can measure the contribution of ADP and TXA2 receptors to clot formation by adding the appropriate agonists.5,20,23 Because Chang et al3 only used the TEG-Kaolin assay, just as some other researchers did, they might not be able to deter-mine significant changes in platelet dysfunction.
In conclusion, different study designs and TEG® reagents may result in different findings during PFA-100® and TEG® studies. In clinical anesthesia practice, coagulation monitoring is very important in certain types of surgery. The PFA-100® can offer good information about platelet function. But TEG® with appropriate reagents may produce more infor-mation about platelet function, coagulation factors, fibrin and fibrinolysis, which are vital in clinical blood transfusion therapy.
Mei-Yung Tsou, MD, PhD
Associate Editor, Acta Anaesthesiologica Taiwanica
Division Chief of Neuroanesthesia,
Department of Anesthesiology,
Taipei Veterans General Hospital and
National Yang-Ming University School of Medicine