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On-line version ISSN 1806-907X
Rev. Bras. Anestesiol. vol.56 no.1 Campinas Jan./Feb. 2006
Thromboelastograph in cardiac surgery: state of the art*
Tromboelastógrafo en cirugía cardíaca: estado actual
Plínio Vasconcelos MaiaI; Graciana Zerbini de AraújoII; Marcos Daniel de Faria, TSAIII
IME3 do CET/SBA HC UFMG
IIME2 do CET/SBA HC UFMG
IIISc. em Engenharia Biomédica; Instrutor do CET/SBA HC UFMG
BACKGROUND AND OBJECTIVES:
Management of hemostasis of cardiopulmonary bypass (CPB) patients is still a
major challenge. New monitoring methods, new hemostatic drugs and new platelet
function inhibitors are being added to the pre, intra and postoperative periods.
The multifactorial nature of CBP-induced hemostasis disorders requires the understanding
of their pathophysiology and the accurate hemostasis evaluation for effective
coagulation during CPB, in addition to the maintenance of adequate postoperative
hemostasis. Activated clotting time (ACT) and coagulogram are not enough for
this management. A broader evaluation is needed with monitors able to measure
platelet function and hemostatic process dynamics as a whole.
CONTENTS: Hemostasis is the result of the balance of coagulation, anticoagulation and fibrinolysis systems components. This balance is disrupted during CPB making patients susceptible to microvascular bleeding. CPB induces multifactorial changes in platelet force growth and clot elastic properties. Blood products are often used and there is the need for protocols to guide transfusion decisions. It is important to determine platelet function with monitors measuring clot visco-elastic properties, such as thromboleastograph (TEG) and Sonoclot.
CONCLUSIONS: Thromboelastograph is an important hemostasis monitor for patients submitted to CPB. It has been incorporated to hemostatic disorders evaluation protocols and transfusion therapy, with good results.
Key Words: MONITORING: thromboelastograph; SURGERY, Cardiac: cardiopulmonary bypass
JUSTIFICATIVA Y OBJETIVOS:
El manejo de la hemostasia en el paciente durante circulación extra-corpórea
(CEC) permanece como un gran desafío. Nuevos métodos de monitorización,
nuevas drogas hemostáticas y nuevos inhibidores de la función plaquetaria
están siendo incorporados en la práctica perioperatoria. La naturaleza
multi-factorial de los disturbios de la hemostasia causados por la CEC exige
conocimiento de la fisiopatología causal y correcta evaluación de
la hemostasia para obtener una anti-coagulación eficaz durante la CEC y
una coagulación normal con hemostasia adecuada luego de la cirugía.
Tiempo de coagulación activado (TCA) y coagulograma no son suficientes
en este manejo. Es necesaria la evaluación amplia, con monitores capaces
de medir la función de las plaquetas y la dinámica del proceso hemostático
en su totalidad.
CONTENIDO: La hemostasia resulta del equilibrio entre los sistemas de coagulación, anti-coagulación y fibrinólisis. Este equilibrio se rompe durante la CEC, tornando al paciente susceptible a sangrados microvasculares. La CEC por varios caminos altera el crecimiento de la fuerza plaquetaria y de las propiedades elásticas del coágulo. El uso e hemoderivados es frecuente y por eso es necesario desarrollar protocolos para orientar la terapia transfusional. Es importante monitorizar la función de las plaquetas con monitores que evalúen las propiedades del coágulo, como el tromboelastógrafo (TEG) y el Sonoclot.
CONCLUSIONES: El TEG es un monitor importante para evaluar la hemostasia de pacientes en CEC. Ha sido incorporado con buenos resultados para orientar la evaluación de disturbios de la hemostasis y de la terapia transfusional.
Perioperative bleeding is a major cause of cardiac surgery morbidity, especially in complex cardiac surgeries with prolonged cardiopulmonary bypass periods1. CPB changes the hemostatic complex inducing coagulation, thrombin formation, subsequent fibrinolysis, platelet activation and dysfunction. These disorders, associated to heparinization and its reversal with protamine, in a patient often presenting with baseline hemostatic system dysfunction2, contribute to further blood loss. This, in turn, leads to increased use of blood products and surgical re-exploration, with increased hospital costs and morbidity, such as transfusion reactions, pulmonary changes and transmission of infections.
Cardiac surgery requires a fast and efficient way to monitor coagulation and fibrinolysis processes, aiming at early detecting hemostatic abnormalities and, in the presence of increased bleeding, at adequately guiding transfusion therapy or indicating surgical exploration.
The thromboelastograph (TEG) described by Hartert in 1948, is a monitor of blood clot visco-elastic properties, which depend on concentration and activity of the elements making up the hemostatic system3. It has been used to diagnose cardiac surgery-related coagulopaties and to develop algorithms for transfusion therapy.
POST-CPB BLEEDING PATHOPHYSIOLOGY
Hemostasis is the result of the dynamic balance of coagulation, anticoagulation and fibrinolysis systems components: blood vessels, platelets, coagulation proteins, natural anticoagulants, fibrinolytic pathway proteins and their inhibitors4. CPB unbalances those systems and predisposes cardiac surgery patients to increased risk of microvascular bleeding5. In spite of protocols and recommendations, the multifactorial nature of post-CPB bleeding generates variability in the use of blood products in different institutions. Mean packed red-cells utilization reaches 50% of surgeries, platelets around 9% and fresh plasma between 0% and 36%, with mean of 6%6. This variation was not explained by differences in patients preoperative profiles, by CPB duration or by estimated perioperative blood loss6.
These data show the need for protocols to guide the use of blood products during cardiac procedures.
Among factors disturbing hemostasis during cardiac surgery there are: induced hypothermia, hemodilution, coagulation activation, endothelial injury, platelet activation and dysfunction and fibrinolytic system activation5. Cardiac patients also present a higher trend to coagulation mechanism activation, associated to deficient fibrinolysis4.
In a study involving 411 cardiac surgery patients, of whom 85% under CPB, factors associated to higher bleeding in the first 24 postoperative hours were: emergency surgery, oral anticoagulants, preoperative low platelet count, prolonged CPB, higher heparin dose, hypothermia intensity, aorta surgery and postoperative metabolic acidosis1.
Hemostasis is activated during CPB resulting in activated factor II production (thrombin). Heparin acts by binding to antithrombin II and increases approximately 1000 times its ability to inactivate some coagulation factors, including thrombin and activated factors IX, X, XI and XII, however its action is not enough to prevent thrombin generation before, during and after CPB7. Thrombin is a powerful platelet activator; its presence during CPB causes platelet activation and dysfunction and its low post-CPB activity, secondary to residual heparin action, contributes to decrease platelet function8.
The fibrinolytic system may be activated by several mechanisms, including hypoxia, activated factor XII, thrombin, and plasminogen activating factor release (t-PA) by the vascular endothelium5,9. During CPB, plasminogen activating factor concentration is rapidly increased, peaking in the postoperative period. It is responsible for converting plasminogen into plasmin, which acts breaking down fibrinogen and fibrin in their degradation products. During CPB, fibrin formation and breakdown is in general a moderate and self-limited process. Occasionally, however, excessive fibrinolysis may contribute to increased bleeding5.
Platelet dysfunction is the major post-CPB bleeding cause10,11 and in pediatric patients, platelet count alone seems to be a major factor12. CPB significantly induces quantitative decrease in platelet force growth and clot elastic properties, and platelet function recovery has been inversely correlated to postoperative non-surgical bleeding8.
This dysfunction is multifactorial including changes in platelet receptors (GpIb e GPIIb-IIIa), thrombocytopenia, hypothermia, fibrinolysis, preoperative anti-platelet drugs2,8,11, postoperative heparin excess or rebound effect11 and excess protamine when anticoagulation is reverted after CPB13. Platelet adhesion is mediated by lb glycoprotein membrane receptor (Gplb), which is destroyed during CPB by plasmin, generated by fibrinolytic system activation and by the wearing caused by blood contact with circuit membranes14. Platelet activation during CPB decreases platelet granules reserves, impairing platelet aggregation (Figure 1).
Platelets play two roles in clot development: tension strength increase and clot retraction. Tension strength depends on platelet concentration and function and is impaired when there is decreased platelet count or platelet dysfunction; retraction, or elastic property, depends on platelet function, fibrinogen concentration, clot structure and hematocryte8. Platelet force growth is not significantly correlated to ACT or APTT8. It is important, then, to determine platelet function to characterize coagulation disorders and to develop algorithms to determine transfusion therapy, aiming at decreasing bleeding and transfused blood products volume15.
Different methods may be used to determine platelet function, and thromboelastrograph (Haemoscope; Roteg), when perioperatively used in transfusion algorithms, has shown to be effective in decreasing the need for blood products and postoperative chest drainage. Other methods to determine post-CPB platelet function are: Sonoclot, Hemostatus (Medtronic Inc), Platelet Works (Helena), Ultegra (Accumetrics), Clotting Time with Platelet Activator (Medtronic Inc), Platelet Function Analyzer PFA-100 (Dade Behring) and aggregometry.
TEG is able to measure in vitro global hemostatic function of a blood sample, documenting platelets interaction with coagulation cascade proteins since the beginning of platelet-fibrin interaction, platelet aggregation and clot development until its eventual lysis. TEG provides an initial evaluation of hemostasis within 20 to 30 minutes, in the OR itself.
Monitor consists of two mechanical parts, a cylindrical cuvette where 0.36 mL of blood are added and a pin suspended by a torsion cable connected to a transducer. The cuvette swings around an axis with angle of 4 degrees and 45 minutes in 10-minute periods and creates a torque, which is transmitted to the blood. With the coagulation process, blood transmits the torque to the pin, which starts to swing together with the cable. The higher the clot viscosity, more the pin oscillation gets closer to cuvette oscillation. Oscillation changes generate an electric signal through the transducer, which is amplified and sent to a computer which, in turn, generates the profile and calculates TEG parameters 16 (Figure 2).
So, clot development is graphically represented by a figure called thromboelastogram, and five parameters arbitrarily identified by Hartert and other authors are obtained16,17 (Chart I and Chart II, Figure 3).
While most conventional coagulation tests are performed as from plasma fractions and examine only isolated parts of the coagulation cascade, TEG provides evaluation with total blood, and its parameters start to be collected exactly where conventional tests end: first fibrin network formation.
Each thromboelastograph has two channels, that is, two sets of cuvette-pin-transducer. Up to eight channels may be connected to the computer. So, each evaluation may be simultaneously performed in different channels, with the addition of activators, plasma, platelet concentrate, heparinase, antifibrinolytics, titrated protamine, aiming not only at coagulopathy diagnosis but also at testing the treatment in vitro.
THROMBOELASTOGRAPH AND CARDIAC SURGERY
Thromboelastograph during cardiac surgeries has been reported since 1987. Recently it is increasing its concernment as the method to analyze coagulation disorders during and after cardiopulmonary bypass. It has been also reported as coagulation monitor for liver transplantation, obstetrics, urology and neonatology18, among other specialties.
Significant TEG indices differences were shown in patients with normal evolution as compared to those with increased bleeding during cardiac surgeries12,19-22. TEG was also beneficial in guiding transfusion therapy for those patients23-25.
Many authors have used TEG to evaluate postoperative predictive bleeding factors after CPB as compared to coagulogram. A study involving 36 patients submitted to cardiac surgery with CPB has compared TEG to platelet function evaluations and to coagulogram. TEG had the best positive predictive factor values (PPV) for increased postoperative bleeding, with PPV of 62.5%. Negative predictive value (NPV) for increased postoperative bleeding was distributed as follows: platelet count below 130 x 109/L (100%); TEG (92.3%); bleeding time above 9 minutes (91.7%); fibrinogen below 175 mg/dL (90%); APTT (85.7%); PA (75%). TEG variables with significant differences between patients with normal and increased postoperative bleeding were: K, alpha angle and MA19.
Cammere et al. have studied 255 patients submitted to cardiac procedures using TEG and platelet function evaluation to identify best predictors for increased postoperative bleeding. Blood samples were collected from arterial catheter in three moments: after anesthetic induction, after patients rewarming still during CPB and 15 minutes after anticoagulation reversal with protamine. TEG was performed with different coagulation activators to obtain faster results.
Samples collected during CPB were treated with heparinase to eliminate the influence of anticoagulation. Platelet function evaluation was performed with PFA-100 (Dade, Behring, Schwalbach, Germany). Routine coagulation tests were also performed, including fibrinogen dosing. Results of PFA-100 tests and alpha angle and MA parameters during modified TEG have shown significant differences between patients with normal and increased postoperative bleeding. Best predictor for increased postoperative bleeding was TEG alpha angle in samples collected after CPB, with PPV of 41%. In line with other studies, TEG variables presented high values for PNV: 85% and 84% for alpha angle and MA, respectively20.
Two studies evaluated TEG and coagulation tests correlation with blood loss in pediatric patients submitted to cardiac procedures with CPB. The first21, prospective involving 75 patients, has shown alpha angle and MA superiority in the correlation of postoperative chest drainage output in patients above 8 kg; for younger children, best predictors were platelet count and fibrinogen levels. An interesting result was the increasing of chest drainage output and of coagulation tests, and increased need for blood products after postoperative fresh-frozen plasma transfusion, when fibrinogen and platelet concentrates had already been infused. The second study12, prospective involving 494 pediatric patients, has compared chest drainage output, need for blood products and coagulation tests. In this study, TEG MA was the only lab test which significantly correlated to total transfused components.
Nuttal et al. have compared TEG, Sonoclot and routine lab tests as post-CPB microvascular bleeding predictors. Lab tests, as opposed to other studies, had the best PPV and NPV. However, TEG and Sonoclot variables reflecting platelet function were also significantly different between groups with normal and increased postoperative bleeding22.
Shore-Lesserson has compared two protocols guiding the use of blood products in patients submitted to complex cardiac procedures: one TEG-based (Chart III) and the other based on routine lab tests (Chart IV). Less blood products were used in the TEG group, with statistically significant difference (p < 0.05) for platelets concentrate and fresh-frozen plasma23. These data are consistent with a pilot study involving 60 patients submitted to complex cardiac procedures, which has also shown decreased need for blood products in the group whose transfusion therapy was guided by TEG24. Another prospective study has shown decreased need for blood products and mediastinal drainage after CPB with the implementation of an algorithm to guide transfusion therapy25.
Spiess et al. have analyzed transfusion therapy data before and after TEG being included as routine for cardiac surgery in their institution. A total of 1079 patients were studied, 591 of whom after TEG implementation. No blood transfusion protocol had been proposed and transfusion decisions depended on the anesthetic and surgical teams in the OR, and on intensive care team in the postoperative period. There has been significant decrease in the use of packed red cells, platelets and fresh-frozen plasma after TEG implementation. Cryoprecipitate use was decreased however with p = 0.091 (non significant) between groups. Investigators have reported that the most impressive result was the decrease in surgical re-exploration due to increased bleeding, possibly attributed to high TEG negative predictive values. The study has also evaluated TEG-related costs: a relatively cheap monitor performing coagulation analysis 50% cheaper as compared to coagulation lab tests, in addition to generating costs savings with blood products and surgical re-exploration26.
Literature data are still inconsistent as to the best way to predict which patients submitted to cardiac procedures will present increased postoperative microvascular bleeding; however, TEG remains as an important hemostasis monitor in the management of these patients.
Low PPV values of TEG are acceptable since not all hemostasis disorders will necessarily increase bleeding; however, in the presence of bleeding, changed TEG values strengthen the hypothesis of bleeding by coagulopathy and give an indication of which coagulation component should be corrected. High negative predictive values of TEG, on the other hand, identify patients with lower risk of increased bleeding by hemostasis disorders; in the presence of bleeding, these patients would probably be submitted to surgical procedures.
TEG was effective, through blood products administration protocols, to decrease the consumption of hemostatic agents during and after cardiac procedures with CPB. These advantages, associated to the unique opportunity to evaluate hemostasis during CPB with heparinase, to relatively low cost, to decreased costs with blood transfusions and surgical re-exploration, to the easiness and fastness with which TEG can be performed, make it an important tool for the team involved in the management of patients to be submitted to cardiac surgery with cardiopulmonary bypass.
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Dr. Marcos Daniel de Faria
Address: Rua Santa Catarina, 755/1502
ZIP: 30170-080 City: Belo Horizonte, Brazil
Submitted for publication June 10, 2005
Accepted for publication November 21, 2005
* Received from do Hospital de Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, MG