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PEDIATRIC ANESTHESIA

Rapid Evaluation of Coagulopathies After Cardiopulmonary Bypass in Children Using Modified Thromboelastography

Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia

Address correspondence to Bruce E. Miller, MD, Department of Anesthesiology, Children’s Healthcare of Atlanta at Egleston, 1405 Clifton Rd., N.E., Atlanta, GA 30322.

	Abstract

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Complex coagulopathies follow cardiopulmonary bypass (CPB) in children. However, objective laboratory data that can be acquired rapidly to guide their management are lacking. Because thromboelastography has proven useful in this regard, we evaluated the use of celite or tissue factor (TF) activation and heparinase modification of blood samples to allow rapid determination of thromboelastogram data in children younger than 2 yr undergoing CPB. Celite or TF activation shortened the initiation of clotting and, thus, the time required for the important thromboelastogram and maximum amplitude values to begin evolving. Although thromboelastogram and maximum amplitude values were increased with these activators, correlations persisted between platelet count or fibrinogen level and each of these values. The additional use of heparinase allowed thromboelastograms to be obtained during CPB with values not different from those obtained without heparinase after protamine administration. Therefore, celite- or TF-activated, heparinase-modified thromboelastograms begun during CPB allow objective data to be available by the conclusion of protamine administration to help restore hemostasis after CPB in children. Thromboelastography identified transient fibrinolysis during CPB in some children that resolved by the conclusion of protamine administration. Future investigations of the effectiveness of modified thromboelastography-guided coagulopathy management after CPB in children are needed.

Implications: Thromboelastography is useful in assessing the coagulopathies that follow cardiopulmonary bypass in children. Modifying blood samples with celite or tissue factor and heparinase allows thromboelastography begun before the termination of cardiopulmonary bypass to become a rapid point-of-care monitor to provide objective data for guiding blood component therapy to manage these coagulopathies.

	Introduction

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Coagulopathies after cardiopulmonary bypass (CPB) are more severe in children than adults (1–4) and are characterized by severe quantitative coagulation factor deficiencies and evidence of activation of the fibrinolytic system (3–6). These hemostatic derangements are extreme in younger (<12 mo), smaller (<8 kg) children (5,7), requiring intervention with blood product transfusions to restore adequate hemostasis in essentially all of this group of children. Although treating these coagulopathies in children is often begun by using only a subjective assessment of the appearance of the operative field as a guide, two pediatric studies have determined correlations between specific coagulation tests and post-CPB chest tube drainage and blood product transfusion requirements (5,6). Use of these correlations could allow objective data to be included in the decision making process of coagulopathy treatment after CPB in children. The use of objective data to guide coagulopathy treatment in adults decreases blood product exposure and re-exploration rates for excessive postoperative bleeding (8,9).

Laboratory tests that correlate with post-CPB chest tube drainage and blood product transfusion requirements in children are platelet count, fibrinogen level, and thromboelastogram values (5,6). For these tests to be clinically useful, however, results must be available by the conclusion of the protamine administration after CPB, and preferably sooner. Platelet counts and fibrinogen levels could be obtained shortly after the onset of CPB because they decrease significantly on the initiation of CPB as a result of hemodilution. However, these factors continue to decrease in number and function during the course of CPB as activation of coagulation and fibrinolytic systems produces a dynamic hemostatic process that results in continuing consumption of these coagulation factors (4,6). Unfortunately, obtaining platelet counts and fibrinogen levels late in the course of CPB or after the termination of CPB is rarely useful because of the long turnaround times before results are available from a central laboratory.

Thromboelastography is a coagulation test that can be performed directly in the operating room. Values measured from the thromboelastogram tracing include R, K, , maximum amplitude (MA), and A-60. The R value, measured from the beginning of the thromboelastogram recording until an amplitude of 2 mm is reached, represents the time necessary for initial clot formation and reflects the function of the intrinsic coagulation pathway. The K value is the time interval from the end of the R value until an amplitude of 20 mm is attained and appraises the rapidity of fibrin build-up and cross-linking as the clot forms. The value similarly assesses this rate of clot formation, is measured as the slope of the outside divergence of the thromboelastogram tracing from the point of the end of the R value, and reflects the function of both fibrinogen and platelets. The MA of the tracing is a reflection of the maximum strength of the fibrin clot and is influenced most importantly by fibrinogen levels, platelet numbers, and platelet function, as well as by factors VIII and XIII. The A-60 value is the amplitude of the thromboelastogram tracing 60 min after the MA has been reached and is useful in measuring clot retraction or lysis by comparing it with the MA value. An A-60:MA ratio of <0.85 has been used to define fibrinolysis (10,11).

Thromboelastogram and MA values have been correlated with post-CPB chest tube drainage and blood transfusion requirements in children (5,6). However, obtaining native thromboelastogram tracings after CPB and heparin reversal is of little clinical use in managing post-CPB bleeding because of the length of time necessary for clotting to begin and the important thromboelastogram and MA values to be obtained in the presence of the severe coagulopathies that exist in children at this time (5,10–12). Studies in adults have shown that the use of celite or tissue factor (TF) to activate coagulation significantly speeds attainment of the thromboelastogram and MA values (13–15). Additionally, the use of heparinase to neutralize circulating heparin in blood samples from adults during CPB allows thromboelastogram tracings to be obtained before the termination of CPB (16,17). Combining these two thromboelastograph modifications in children undergoing CPB could allow thromboelastogram data to be rapidly obtained just before the termination of CPB and, therefore, fulfill the goal of having pertinent objective data available to help guide coagulopathy management immediately after CPB in children.

Therefore, our objectives in this study of children undergoing cardiac surgery requiring CPB were 1) to evaluate the effects of celite and TF activation on thromboelastogram parameters; 2) to determine the correlation of activated thromboelastogram and MA values with other predictive coagulation tests after CPB; and 3) to evaluate the use of heparinase in vitro in allowing thromboelastograms to be obtained during the fully heparinized state of CPB in children.

	Methods

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After human investigations committee approval, 85 children less than 2 yr old scheduled for cardiac surgery requiring CPB were enrolled. None of these children was receiving aspirin, warfarin, heparin, or platelet inhibitors. The thromboelastograph effects of celite or TF activation of blood were studied in 35 children (Group I). Thromboelastogram tracings were obtained by using a Thrombelastograph Coagulation Analyzer^® (Haemoscope Corporation, Skokie, IL), and R, K, , and MA variables were measured. The tracings were also observed for evidence of fibrinolysis (rapidly diminishing amplitude after attainment of the MA). Baseline platelet count and fibrinogen level were obtained preoperatively. After the induction of anesthesia and placement of monitoring lines, a 3-mL sample of blood was drawn from either the arterial or central venous line after aspirating 5 mL of blood to clear the line of heparin from the flush system. A 0.36-mL aliquot of this sample was then used to run a native, unactivated thromboelastogram tracing by using established techniques. A 1-mL aliquot of the sample was placed into a vial containing 90 µL of celite particles in normal saline (Haemoscope Corporation). The vial was inverted five times to insure adequate mixing of the blood and celite, and 0.36 mL of this aliquot was used to obtain a celite-activated thromboelastogram tracing. Then, a 0.35-mL aliquot of the original blood sample was placed into a thromboelastograph cup containing 10 µL of 1% TF to obtain a TF-activated thromboelastogram tracing. The pin of this thromboelastograph channel was raised and lowered into the cup five times to insure adequate mixing of the blood and TF. These three thromboelastogram tracings were begun and allowed to run until at least the MA had been reached. After the conclusion of CPB, administration of protamine (1 mg per mg of initially administered heparin), and return of the activated clotting time to baseline values, platelet count and fibrinogen level as well as native, celite-activated, and TF-activated thromboelastogram tracings were repeated in these 35 children.

The effect of heparinase on thromboelastogram tracings was then studied in 50 other children undergoing CPB (Group II). Before the termination of CPB and after rewarming to at least 34°C, a 3-mL sample of blood was obtained from the bypass circuit. A 1-mL aliquot of this blood was mixed with celite as previously described. This celite-activated blood was then immediately added to a second vial containing 4 IU of lyophilized Heparinase I isolated from Flavobacterium heparinum (Haemoscope Corporation). After inverting this vial five times to once again insure adequate mixing, a thromboelastogram tracing was obtained by using 0.36-mL of this celite-activated, heparinase-modified blood. Another 1 mL aliquot of the original blood sample was added to a second heparinase-containing vial and mixed as described above. From this aloquot, 0.35 mL was then added to a thromboelastograph cup containing 10 µL of 1% TF, and adequate mixing was insured by raising and lowering the pin into the cup five times, thus allowing a TF-activated, heparinase-modified thromboelastogram tracing to be obtained. After the termination of CPB, administration of protamine, and return of the activated clotting time to baseline values, celite- and TF-activated thromboelastogram tracings without heparinase were repeated as previously described.

Analysis of variance was used to ascertain whether differences existed in native, celite-activated, or TF-activated thromboelastograms both at baseline and after protamine administration. Comparisons of individual variables were then made by using two-sample t-test assuming unequal variance with Bonferroni correction for multiple comparisons. The Pearson product-moment correlation coefficient was calculated to determine the relationships between platelet count or fibrinogen level and thromboelastogram and MA values. Paired two-sample t-test for means was used to compare the thromboelastogram values obtained before the termination of CPB using heparinase with those obtained after protamine administration without heparinase for each of the activators. Because fibrinolysis was detected in the thromboelastogram tracings of several children during CPB, two-sample t-test assuming unequal variance and Fisher’s exact test were used to compare variables between children who did and those who did not exhibit this finding. Significance was defined as P < 0.05 for all comparisons.

	Results

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Demographic data are shown in Table 1 . Comparisons of celite- or TF-activated thromboelastogram values to native values at baseline and after protamine show significantly shorter R and K values and greater and MA values in activated samples (Table 2 ). The sum of the baseline R plus K values, which represents the delay before the important predictive thromboelastogram variables and MA can be obtained, decreased significantly from an average of 68.7 mm in the native thromboelastograms to 12.1 mm in celite-activated thromboelastograms (P < 0.0001) and 6.5 mm in TF-activated thromboelastograms (P < 0.0001). Because the thromboelastogram tracing is recorded at a speed of 2 mm/min, the baseline native R plus K sum converts to 34.4 min, with the celite-activated sum becoming 6.0 min and the TF-activated sum becoming 3.25 min. The baseline values more than doubled after activation with either celite or TF (P < 0.0001 for both), whereas the activated MA values were approximately 25% greater than the native MA values (P < 0.0001 for both). After protamine administration, similar effects on the thromboelastogram were found with celite and TF activation. (Figure 1 ) The average postprotamine native R plus K sum was 78.4 mm (39.2 min) and decreased to 30.2 mm (15.1 min) after celite activation (P < 0.0001) and 12.9 mm (6.5 min) after TF activation (P < 0.0001). The values again increased significantly (by 53% with celite [P = 0.001] and 87% with TF [P < 0.0001]) whereas the MA values were 30% greater than native values after activation (celite: P = 0.21; TF: P = 0.002). Comparison of celite with TF activated values shows significantly shorter R values with TF activation (P < 0.0001 at baseline and after protamine) but no differences in K, , or MA values between the two activators at either time point.

View larger version (184K): [in this window] [in a new window]   Figure 1. Native, celite-activated, and tissue factor-activated thromboelastogram tracings after protamine administration in one patient demonstrating the accelerated initiation of clotting with only modest alteration of maximum amplitude produced by the activators.

Comparison of celite-activated thromboelastograms performed during CPB using heparinase in vitro to neutralize circulating heparin to those begun after protamine administration without adding heparinase shows significant differences only in the R values (P < 0.0001). K, , and MA values were not significantly different between these sets of tracings (P = 0.60, 0.31, 0.25 respectively). Comparison of thromboelastograms performed as above but with TF activation reveals significant differences in R (P = 0.008) and (P = 0.004) values, but again no differences in K (P = 0.051) and MA (P = 0.80) values. (Table 3 , Figure 2 )

View larger version (118K): [in this window] [in a new window]   Figure 2. Celite- and tissue factor-activated thromboelastogram tracings in one patient demonstrating the similarity between thromboelastograms performed during cardiopulmonary bypass with heparinase and those performed after CPB and protamine administration without heparinase.

View larger version (127K): [in this window] [in a new window]   Figure 3. Thromboelastogram evidence of fibrinolysis during cardiopulmonary bypass and its resolution in the postprotamine tracing. Complete lysis of the clot is seen 32 min (64 mm) after attainment of the MA in the top tracing. Both thromboelastograms are celite-activated.

	Discussion

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We chose to study only children less than two years old to insure the homogeneity of a true pediatric study population and because of the complex coagulopathies these children exhibit after CPB. Previous reports have suggested that the magnitude of these post-CPB coagulopathies enhances the utility of coagulation tests in children (6). The ability to rapidly acquire coagulation data would provide very useful information to help guide post-CPB coagulopathy management in children.

We used two steps to prove that thromboelastography can become a timely point-of-care coagulation monitor after pediatric CPB. Although its use in predicting the severity of post-CPB coagulopathies in children and in evaluating their management has already been reported (5,6,12), the length of time required for clotting to begin (as reflected in thromboelastogram R and K values) and the important thromboelastogram and MA values to be attained in unactivated blood after protamine administration prevents useful thromboelastogram data from being available when it is clinically needed after CPB. Activation of blood with celite or TF accelerates the onset of clotting (13–15). Celite consists of chemically inert particles (silica) that accomplish this acceleration by providing a contact surface to activate factor XII and platelets, whereas TF is a specific activator of the extrinsic coagulation pathway. Use of these activators reduces the baseline native R plus K sum from 34.4 minutes to 6.0 minutes with celite and 3.25 minutes with TF and reduces the postprotamine native R plus K sum from 39.2 minutes to 15.1 minutes with celite and 6.5 minutes with TF. Therefore, the use of either activator, but especially TF, significantly speeds coagulation and hastens the attainment of thromboelastogram and MA values.

Use of these activators, however, also affects the thromboelastogram and MA values. The values are more significantly affected than the MA values, but are less altered after protamine administration (the most useful point for coagulopathy management) than at baseline. Platelet count and fibrinogen level significantly correlate with both celite- and TF-activated values after the administration of protamine. The MA values are increased by only approximately 30% after activation at either time point and also retain significant correlations with platelet count and fibrinogen level both at baseline and after protamine administration with either activator. New thresholds will be needed to define the activated thromboelastogram and MA values that should trigger interventions for post-CPB coagulopathy management.

Even with the quicker attainment of thromboelastogram and MA values that is accomplished by the use of celite- or TF-activation of clotting, clinicians must still wait 6.5 (TF) to 15 (celite) minutes after protamine administration to begin acquiring useful thromboelastogram data in children. In adults, the use of heparinase neutralizes circulating heparin and allows thromboelastograms to be performed even during CPB (9,16,17). We found, in children, that thromboelastograms run during CPB after rewarming by using heparinase combined with either celite or TF produces data that are similar to activated thromboelastograms begun after protamine administration without heparinase. This finding means that modified thromboelastograms can be started before the termination of CPB and quickly provide useful information even before the termination of CPB and the administration of protamine. This timely, objective data should be useful in deciding when and how to intervene in managing post-CPB coagulopathies in children.

In 7 (14%) of the 50 children in the heparinase limb of this study, fibrinolysis was seen in the heparinase-modified thromboelastograms run before the termination of CPB. Activation of the fibrinolytic system during CPB has been documented previously in children by using protamine-modified thromboelastograms and other laboratory markers with an incidence of approximately 16% and an increased frequency in children less than 12 months old (4,6,18). Fibrinolysis also has been demonstrated in adults with heparinase-modified thromboelastograms (16) but with a much smaller incidence (1 of 51 patients). Thrombin generation (19) and alterations of tissue plasminogen activator to plasminogen activator inhibitor ratios (4) during CPB may lead to this activation of fibrinolysis. In our patients, the fibrinolysis had resolved without intervention in the thromboelastograms performed after protamine administration, yet before coagulation product transfusion, thus leading us to consider the influence of protamine in this area. Interestingly, no differences in demographic factors, CPB data, or postoperative chest tube drainage were found between the children with or without fibrinolysis during CPB, but our number of patients was small.

In summary, this investigation demonstrates that the use of celite or TF to activate coagulation and the use of heparinase to neutralize circulating heparin allows thromboelastography to become a real point-of-care coagulation monitor in the operating room for assessing post-CPB coagulopathies in children. Important predictive thromboelastogram data not only can be obtained rapidly but also while the child is still on CPB, thus permitting pertinent objective data to be immediately available to guide the restoration of hemostasis after protamine administration. Unexpected findings are occasionally encountered (i.e., fibrinolysis), but serial thromboelastograms can determine the functional significance of these occurrences. Prospective pediatric studies should be undertaken to evaluate the effect of the clinical application of these modified thromboelastograms on post-CPB blood loss and blood product usage.

	Acknowledgments

 
The authors would like to thank Jennifer Miller for her clerical assistance in the preparation of this manuscript.

	References

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1. Bachmann F, McKenna R, Cole ER, Najafi H. The hemostatic mechanism after open-heart surgery. I. Studies on plasma coagulation factors and fibrinolysis in 512 patients after extracorporeal circulation. J Thorac Cardiovasc Surg 1975;70:76–85.[Abstract]
2. Mammen EF, Koets MH, Washington BC, et al. Hemostasis changes during cardiopulmonary bypass surgery. Semin Thromb Hemost 1985;11:281–92.[Web of Science][Medline]
3. Kern FH, Morana NJ, Sears JJ, Hickey PR. Coagulation defects in neonates during cardiopulmonary bypass. Ann Thorac Surg 1992;54:541–6.[Abstract]
4. Chan AKC, Leaker M, Burrows FA, et al. Coagulation and fibrinolytic profile of paediatric patients undergoing cardiopulmonary bypass. Thomb Haemost 1997;77:270–7.[Web of Science][Medline]
5. Miller BE, Mochizuki T, Levy JH, et al. Predicting and treating coagulopathies after cardiopulmonary bypass in children. Anesth Analg 1997;85:1196–202.[Abstract]
6. Williams GD, Bratton SL, Riley EC, Ramamoorthy C. Coagulation tests during cardiopulmonary bypass correlate with blood loss in children undergoing cardiac surgery. J Cardiothorac Vasc Anesth 1999;13:398–404.[Web of Science][Medline]
7. Williams GD, Bratton SL, Ramamoorthy C. Factors associated with blood loss and blood product transfusions: a multivariate analysis in children after open-heart surgery. Anesth Analg 1999;89:57–64.[Abstract/Free Full Text]
8. 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.[Web of Science][Medline]
9. Shore-Lesserson L, Manspeizer HE, DePerio M, et al. Thromboelastography-guided transfusion algorithm reduces transfusions in complex cardiac surgery. Anesth Analg 1999;88:312–9.[Abstract/Free Full Text]
10. Tuman KJ, Spiess BD, McCarthy RJ, Ivankovich AD. Comparison of viscoelastic measures of coagulation after cardiopulmonary bypass. Anesth Analg 1989;69:69–75.[Abstract/Free Full Text]
11. Spiess BD, Tuman KJ, McCarthy RJ, et al. Thromboelastography as an indicator of post-cardiopulmonary bypass coagulopathies. J Clin Monit 1987;3:25–30.[Medline]
12. Martin P, Horkay F, Rajah SM, Walker DR. Monitoring of coagulation status using thrombelastography during paediatric open heart surgery. Int J Clin Monit Comput 1991;8:183–7.[Web of Science][Medline]
13. Sharma SK, Philip J, Wiley J. Thromboelastographic changes in healthy parturients and postpartum women. Anesth Analg 1997;85:94–8.[Abstract]
14. Yamakage M, Tsujiguchi N, Kohro S, et al. The usefulness of celite-activated thromboelastography for evaluation of fibrinolysis. Can J Anaesth 1998;45:993–6.[Web of Science][Medline]
15. McCarthy RJ, Stancic Z, Mei J, et al. Use of recombinant human tissue factor (RTF) thromboplastin as an adjunct to whole blood thromboelastograph (TEG) coagulation monitoring. Anesth Analg 1996;82:S306.
16. Tuman KJ, McCarthy RJ, Djuric M, et al. Evaluation of coagulation during cardiopulmonary bypass with a heparinase-modified thromboelastographic assay. J Cardiothor Vasc Anesth 1994;8:144–9.[Medline]
17. Spiess BD, Wall MH, Gillies BS, et al. A comparison of thromboelastography with heparinase or protamine sulfate added in vitro during heparinized cardiopulmonary bypass. Thromb Haemost 1997;78:820–6.[Web of Science][Medline]
18. Williams GD, Bratton LS, Nielsen NJ, Ramamoorthy C. Fibrinolysis in pediatric patients undergoing cardiopulmonary bypass. J Cardiothorac Vasc Anesth 1998;12:633–8.[Web of Science][Medline]
19. Slaughter TF, LeBleu TH, Douglas, Jr JM, et al. Characterization of prothrombin activation during cardiac surgery by hemostatic molecular markers. Anesthesiology 1994;80:520–6.[Web of Science][Medline]

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999