Thromboelastography®: Past, Present, and Future

1223 EDITORIAL VIEWS Anesthesiology 2000; 92:1223–5 © 2000 American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc. Thromboelastography® Past, Present, and Future General The use of the TEG® to monitor whole-blood coagulation was first described by Hartert in 1948.2 The TEG® r This Editorial View accompanies the following article: Camenzind V, Bombeli T, Seifert B, Jamnicki M, Popovic D, Pasch T, Spahn DR: Citrate storage affects Thrombelastograph® analysis. ANESTHESIOLOGY 2000; 92:1242–9. Accepted for publication January 20, 2000. Key words: Blood; coagulation; measurement techniques; transfusion. Dr. Whitten is currently a clinical investigator for Bayer Corporation, New Haven, Connecticut, and Alliance Pharmaceutical, San Diego, California, and has performed published protocols using a thromboelastogram that was donated to his department from Haemascope Corporation, Skokie, Illinois. Dr. Greilich is currently a clinical investigator for Bayer Corporation, New Haven, Connecticut, and Biopure Corporation, Cambridge, Massachusetts, and is the principal investigator of a study funded by grants (VISN17) from the Department of Veterans Affairs, Dallas, Texas, and the Society of Cardiovascular Anesthesiologists, Richmond, Virginia, which uses the Thromboelastograph as a bioassay. Both Dr. Whitten and Dr. Greilich are currently participating in research protocols for which Haemascope Corporation has provided cups and pens for the TEG® machines at a discount rate. Anesthesiology, V 92, No 5, May 2000 measures shear elastic modulus (dynes per centimeters squared) during clot formation in whole or recalcified citrated blood.2,3 The global nonspecific nature of the TEG® measurement may be both its greatest weakness and strength. Although specific coagulation assays rarely correlate with blood loss, they do provide specific diagnoses that respond to specific treatments. The TEG® maximum amplitude (MA) is a complex integrated measurement that has been associated with blood loss. The chief limitations of the TEG® include its: (1) inability to diagnose a specific hemostatic lesion; (2) weak correlation with specific assays (prothrombin and activated partial thromboplastin times); and (3) inability to consistently detect benefits of fractionated blood product therapy.4 Since 1948, the technique has enjoyed periods of popularity but has never achieved widespread use in the United States. In the early 1980s, the TEG® was used routinely for coagulation monitoring during liver transplantation.5 The TEG® has now found additional applications in a diverse group of clinical settings, including cardiovascular surgery, obstetric anesthesia, and trauma anesthesia (massive transfusion). Liver Transplantation Downloaded from http://pubs.asahq.org/anesthesiology/article-pdf/92/5/1226/651259/0000542-200005000-00008.pdf by guest on 11 September 2022 THIS issue of ANESTHESIOLOGY contains an article by Camenzind et al.1 regarding the influence of citrate storage on thromboelastography® (TEG® Haemascope Corp.). Although the TEG® is most commonly performed on a native (uncitrated) sample, the use of citrated blood permits longer delays after sample acquisition, thus facilitating ancillary or research laboratory analysis. Camenzind et al.1 nicely outline some of the issues related to the impact of sample storage on the TEG®. Anesthesiology, as a specialty, has taken a leading role in evaluating the TEG® as a nearsite monitor of hemostasis in several clinical settings. Many issues, however, remain unresolved about how to use the TEG® to guide clinical decision-making. The purpose of this Editorial View is to briefly review studies that have lead to current applications of the TEG® and to outline future challenges that need to be addressed for its broader use. Each of the three phases of orthotopic hepatic transplantation has associated metabolic, hemorrhagic, and other derangements that complicate the preexisting coagulopathy present in these patients. Transfusion requirements are highly variable, but sudden massive blood loss occurs in conjunction with hyperfibrinolysis, coagulation factor and inhibitor deficiencies, and/or thrombocytopenia. Without prompt and effective treatment, these complicated clinical coagulopathies can result in dramatic hemorrhagic consequences. Kang et al.5 demonstrated that the use of the TEG® for monitoring hemostasis during liver transplantation decreases blood transfusion requirements. However, a study of low-dose tranexamic acid showed that inhibition of fibrinolysis as measured by the TEG® during orthotopic hepatic transplantation had no influence on transfusion of blood products.6 1224 EDITORIAL VIEWS Cardiovascular Surgery Trauma Anesthesia ® Obstetric Anesthesia The physiology of pregnancy results in a hypercoagulable state that prepares the parturient for the hemorrhage of childbirth. Several factors involved in the coagulation cascade and platelet reactivity increase during pregnancy, while naturally occurring anticoagulants decrease. The TEG® is capable of detecting the hypercoagulable state of normal parturients and the coagulopathy associated with pregnancy-induced hypertension or preeclampsia.14 Preeclampsia is associated with thrombocytopenia, coagulation factor deficiencies, and, in severe cases, disseminated intravascular coagulation. Although the risk of abnormal hemostasis increases with the severity of preeclampsia, Sharma et al.14 could not determine whether decreases in the TEG® MA were related to altered platelet function or coagulation factor deficiencies (most notably fibrinogen). The ability to identify which patients with moderate–severe pregnancy-induced hypertension can safely receive the benefit of epidural analgesia remains to be elucidated. Anesthesiology, V 92, No 5, May 2000 Massive trauma results in a profound coagulopathy associated with thrombocytopenia, coagulation factor deficiency, and hypothermia. In addition to detecting thrombocytopenia/thrombocytopathy and coagulation factor deficiency, the TEG® has also been shown to be responsive to the influence of hypothermia.15 In a recent study by Kaufman et al.16 only the injury severity score and the TEG® were predictive of early transfusion. Historically, patients with an intense systemic response to massive penetrating and/or blunt trauma will almost immediately develop a hypocoagulable state. If surgical control of bleeding cannot be obtained rapidly, the ensuing coagulopathy can be severe in nature and will require aggressive resuscitation. The use of the TEG® to reduce the morbidity and mortality associated with bleeding and transfusion therapy in a major trauma center needs to be explored. Future Challenges for TEG® Downloaded from http://pubs.asahq.org/anesthesiology/article-pdf/92/5/1226/651259/0000542-200005000-00008.pdf by guest on 11 September 2022 Many clinicians believed that the TEG would be useful in determining which component of hemostasis (thrombocytopenia/thrombocytopathy, coagulation factor deficiencies, hyperfibrinolysis) is the primary cause of the coagulopathy associated with cardiopulmonary bypass surgery. Although several studies have demonstrated that the TEG® MA is associated with excessive hemorrhage, its direct correlation with blood loss has never been established.7–9 Studies in both pediatric and adult populations demonstrate that the TEG® MA is no better than platelet count for prediction of blood loss after cardiopulmonary bypass.10,11 The TEG® MA has been found in several studies to demonstrate good accuracy and even a better negative predictive value for excessive blood loss after cardiac surgery.7–9 The high negative predictive value can facilitate early identification and appropriate treatment of surgical bleeding by distinguishing it from a significant coagulopathy. Incorporation of the TEG® into clinical decision-making has resulted in decreased blood loss and transfusions in one large retrospective and two prospective studies.8,9,12 Finally, Tuman et al.13 demonstrated that heparinase-treated whole blood may be used to measure the TEG® during cardiopulmonary bypass to facilitate prompt treatment of significant coagulopathy immediately after heparin reversal. Although standard laboratory tests are poor predictors of bleeding, transfusion medicine specialists have been reluctant to accept whole-blood assays.17 Their justification has been: (1) the nonspecific nature of the TEG® measurement; (2) lack of quality-assurance methodologies required by regulatory agencies such as the American Association of Blood Banks, Federal Drug Administration, and College of American Pathologists; and (3) insufficient scientific evidence or appropriately powered outcome studies. Any near-site bioassays intended to guide clinical decision-making must adhere to rigid guidelines with respect to clear clinical and laboratory indications, quality assurance, and hospital-specific laboratory transfusion “triggers.” Institutions that have undertaken this rigorous task have seen significant improvements in their clinical practice.9 Many transfusion medicine specialists feel that nearsite hemostasis monitoring could significantly improve clinical decision-making in patients undergoing surgery. Until recently, the vast majority of studies using the TEG® have been descriptive in design and, therefore, have had a limited impact on clinical decision-making. The next major advance will require a multicenter, interdisciplinary approach to design the studies needed to establish evidence-based transfusion algorithms. If multidisciplinary teams do not address these remaining issues, use of the TEG® in the perioperative period will remain limited. 1225 EDITORIAL VIEWS References 1. Camenzind V, Bombeli T, Seifert B, Jamnicki M, Popovic D, Pasch T, Spahn DR: Citrate storage affect Thromboelastograph® analysis. ANESTHESIOLOGY 2000; 92:1242–9 2. Hartert H: Blutgerinnung studien mit der thromboelastographie, einen Neuen Untersuchingsverfahren. Klin Wochenschr 1948; 26:577– 83 3. Hartert H, Schaeder JA: The physical and biological constraints of thromboelastography. Biorheology 1962; 1:31–9 4. Zuckerman L, Cohen E, Vagher JP, Woodward E, Caprinia JA: Comparison of thromboelastography with common coagulation tests. Thromb Haemostas 1981; 46:752– 6 5. Kang YG, Martin D, Marquez J, Lewis JH, Bontempo FA, Shaw BW Jr, Starzl TE, Winter PM: Intraoperative changes in blood coagulation and thrombelastographic monitoring in liver transplantation. Anesth Analg 1985; 64:888 –97 6. Kaspar M, Ramsay MAE, Nguyen A-T, Cogswell M, Hurst G, Ramsay KJ: Continuous small-dose tranexamic acid reduces fibrinolysis Anesthesiology, V 92, No 5, May 2000 but not transfusion requirements during orthotopic liver transplantation. Anesth Analg 1997; 85:281–5 7. Tuman KJ, Spiess BD, McCarthy RJ, Ivankovich AD: Comparison of viscoelastic measures of coagulation after cardiopulmonary bypass. Anesth Analg 1989; 69:69 –75 8. Mongan PD, Hosking MP: The role of desmopressin acetate in patients undergoing coronary artery bypass surgery. ANESTHESIOLOGY 1992; 77:38 – 46 9. Spiess BD, Gillies BSA, Chandler W, Verrier E: Changes in transfusion therapy and reexploration rate after institution of a blood management program in cardiac surgical patients. J Cardiothorac Vasc Anesth 1995; 9:168 –73 10. Miller BE, Mochizuki T, Levy JH, Baily JM, Tosone SR, Tam VK, Kanter KR: Predicting and treating coagulopathies after cardiopulmonary bypass in children. Anesth Analg 1997; 85:1196 –202 11. Ereth MH, Nuttall GA, Klindworth JT, MacVeigh I, Santrach PJ, Orszulak TA, Harmsen WS, Oliver WC Jr: Does the platelet-activated clotting test (HemoSTATUS®) predict blood loss and platelet dysfunction associated with cardiopulmonary bypass? Anesth Analg 1997; 85:259 – 64 12. Shore-Lesserson L, Manspeizer HE, DePerio M, Francis S, VelaCantos F, Ergin MA: Thromboelastography-guided transfusion algorithm reduces transfusion in complex cardiac surgery. Anesth Analg 1999; 88:312–9 13. Tuman KJ, McCarthy RJ, Djuric M, Rizzo V, Ivankovich AD: Evaluation of coagulation during cardiopulmonary bypass with a heparinase modified thromboelastographic assay. J Cardiothorac Vasc Anesth 1994; 8:144 –9 14. Sharma SK, Phillip J, Whitten CW, Padakandla WB, Landers DF: Assessment of changes in coagulation in parturients with preeclampsia using thromboelastography. ANESTHESIOLOGY 1999; 90:385–90 15. Douning LK, Ramsay MAE, Swygert TH, Hicks KN, Hein HA, Gunning TC, Suit CT: Temperature corrected thromboelastography in hypothermic patients. Anesth Analg 1995; 81:608 –11 16. Kaufman CR, Dwyer KN, Cruz JD, Dols SJ, Trask AL: Usefulness of thromboelastography in assessment of trauma patient coagulation. J Trauma 1997; 42:716 –20 17. Gelb AB, Roth RI, Levin J, London MJ, Noall RA, Hauck WW, Cloutier M, Verrier E, Mangano DT: Changes in blood coagulation during and following cardiopulmonary bypass. Am J Clin Pathol 1996; 106:87–99 Downloaded from http://pubs.asahq.org/anesthesiology/article-pdf/92/5/1226/651259/0000542-200005000-00008.pdf by guest on 11 September 2022 Charles W. Whitten, M.D. M. T. “Pepper” Jenkins Professor of Anesthesiology Department of Anesthesiology and Pain Management The University of Texas Southwestern Medical Center at Dallas Director of Anesthesiology and Pain Management (Surgical Services) Parkland Health and Hospital System Dallas, Texas 75235-9068 [email protected] Philip E. Greilich, M.D. Assistant Professor of Anesthesiology Division of Cardiovascular/Thoracic Anesthesiology Department of Anesthesiology and Pain Management The University of Texas Southwestern Medical Center at Dallas Director, Platelet Function Studies Research Laboratory Dallas Veterans Affairs Medical Center Dallas, Texas 75216 [email protected]