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British Journal of Anaesthesia 1992; 69: 307-313REVIEW ARTICLE

THROMBELASTOGRAPHYS. V. MALLETT AND D. J. A. COX

In the past decade, there has been an increasingdemand on transfusion services as complex surgicalprocedures associated with significant blood loss andcoagulopathy become more common. Blood andblood products are becoming an increasingly scarceand precious resource, but their use carries some risk[24,42]. It is mandatory, therefore, that bloodcomponent therapy is justifiable: the use of clottingfactors and platelet transfusions on an empiricalbasis to treat real or perceived haemostatic defects isno longer acceptable.Clotting is a dynamic process which is difficult tomeasure using static end-points, which provide noinformation about the quality of the clot or thedynamics of its formation. Conventional coagulationscreens (plasma thromboplastin (PT), partial throm-boplastin time (PTT), platelet count and fibrinogenconcentrations) are frequently inadequate for thepurpose of monitoring coagulation when there maybe many potential haemostatic defects and continuedblood loss may make difficult interp retatio n of resultsfrom samples taken previously.Another problem with routine coagulation tests isthat what is regarded as "normal" for the generalpopulation may not necessarily be "normal" for apatient who has undergone major surgery withoutexcessive blood loss. The anaesthetist managing ableeding patient requires a method of monitoringcoagulation that is simple, sensitive and reliable andthat indicates in a reasonable time scale the nature ofthe haemostatic defect.Because of the limitations of standard coagulationtests, several centres have been re-examining tech-niques such as thrombelastography (TEG), thatmonitor haemostasis as a whole dynamic process,rather than as isolated end-points.

THROMBELASTOGRAPHYThrombelastography was developed first by Hartertin 1948 [9]. It remained largely a research tool anddid not gain widespread usage in clinical practice.However, in the past few years there has been aresurgence of interest in techniques that evaluate theviscoelastic properties of whole blood during theperioperative period [16]. TEG enables a globalassessment of haemostatic function to be made froma single blood sample, documenting the inter-

reaction of platelets with the protein coagulationcascade from the time of the initial platelet-fibrininteraction, through platelet aggregation, clotstrengthening and fibrin cross linkage to eventualclot lysis. The "signature" of generated tracings cangive information on clotting factor activity, plateletfunction and any clinically significant fibrinolyticprocess, within 20-30 min. The Thrombelastograph(Haemoscope Corp. & Launch Diagnostics) is asmall instrument that can be set up easily in theoperating or anaesthetic room. By virtue of its havingtwo separate channels, it is possible to perform serialblood coagulation profiles. This allows coagulationto be monitored directly at regular intervals.Principles of thrombelastography

In essence, the TEG consists of two mechanicalpa rts: a heated (37 C) cuvette or cup, w hich isoscillated and a pin which is suspend ed freely froma torsion wire (fig. 1). The freshly drawn blood(0.35 ml) is placed in the cuvette a nd, whilst thesample remains liquid, the motion of the cuvettedoes not affect the pin. However, when clot starts toform, the fibrin strands "couple" the motion of thecup to the pin and the shear modulus and elasticity

Torsion wire

Cup(Whole b lood 0.36 ml)

Fibrin strand

F I G . 1. Principles of thrombelastography.

KEY WORDSBlood: coagulation,graphy. Measurem ent techniques: thromb elasto- S. V. MALLE TT, F.R.C.ANAES. ; D. J . A. Cox, M.SC. ; Department ofAnaesthesia, Royal F ree Hospital, Pond Street, London NW 32QG. Accepted for Publication: April 2, 1992.

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308 BRITISH JOURNAL OF ANAESTHESIA

h - Thrombosis FibrinolysisFIG. 2. Quantification of TEG variables. Analysis of the Thrombelastograph. r = Reaction rime (time from sampleplacement in the cuvene u ntil TE G tracing am plitude reaches 2 mm (normal range 6-8 m in)). This represents the rateof initial fibrin formation and is related functionally to plasma clotting factor and circulating inhibitor activity(intrinsic coagulation). Prolongation of the r time may be a result of coagulation factor deficiencies, anticoagularion(heparin) or severe hypofibrinogenacmia. A small r value may be present in hypercoagulability syndromes. K = clotformation time (normal range 3 -6 min); measured from r time to the point where the amplitude of the tracing reaches20 mm. The coagulation time represents the time taken for a fixed degree of viscoelasticity to be achieved by theforming clot, as a result of fibrin build up and cross linking. It is effected by the activity of the intrinsic clotting factors,fibrinogen and platelets. Alpha angle (a) (normal range 50-60) = angle formed by the slope of the TEG tracing fromthe r to the K value. It de notes speed at which solid clot forms. Decreased values may occur with hypofibrinogenaemiaand thrombocytopenia. Maximum amplitude (MA) (normal range 50-60 mm) = greatest amplitude on the TEG traceand is a reflection of the absolute strength of the fibrin clot. It is a direct function of the maximum dynamic propertiesof fibrin and platelets. Platelet abnorm alities, whether qualitative or quantitative, substantially disturb the MA. A,,(normal range = MA 5 mm) = amplitude of the tracing 60 min after MA is achieved. It is a measure of clot lysis orretraction. The clot lysis index (CLI) (normal range > 8 5 % ) is derived as A ^ /M A x 100(%). It measures theamplitude as a function of time and reflects loss of clot integrity as a result of lysis.

of the clot is then transmitted through the pin, andamplified to give the TEG trace, which is recordedon heat-sensitive paper moving at a rate of2 mm min"1 (fig. 2).TE G vs conventional coagulation testsTEG enables a complete evaluation of the processof clot initiation and the structural characteristics ofthe formed clot and its stability [18]. Routinelaboratory tests are generally performed on centri-fuged plasma fractions and examine only isolatedportions of the coagulation cascade, thereby over-looking important interactions essential to the clini-cal evaluation of clotting and bleeding syndromes[21].Many of the conventional coagulation tests endwith the formation of the first fibrin strands, whileTEG begins at this point and continues to generatedata as clotting continues through to eventual clotlysis or retraction. Although there is some correlationbetween TEG variables and common coagulationtests [11,35,44] because the TEG variables areinter-dependent, measuring the interaction of theclotting cascade and platelets in whole blood and notlooking at isolated end-points, there is not an exactrelationship between the two. Zuckerman [44]emphasized that these additional data from the TEGmake it more sensitive for detecting changes in thehaemostatic balance of coagulation and relatedsystems."Bedside" coagulation tests are now available forPT and PTT. However, these tests do not have a

high predictive value for perioperative bleeding [35]and th ere have been no studies th at directly correlateabnormal values with surgical blood loss. Indeed,because they give no information about the vital

interaction between platelets and the coagulationcascade, it is theoretically possible to have normalPT and PTT values but still have active bleedingas a result of abnormal haemostasis.Adequate platelet function is essential for normalhaemostasis. A normal platelet count does not enablethe anaesthetist to make any assumptions on plateletactivity. Tem plate bleeding tim es are often difficultand impractical to obtain during operation, and maybe subject to inaccuracies unless performed byexperienced personnel [28]. In vitro platelet functiontests are complex and labour intensive, and are alsoimpractical for the acute intraoperative situation.Significant correlations exist between the maximumamplitude on the TEG and platelet count and alsowith aggregation responses to collagen and ADP[39]. The TEG may be useful, therefore, for in vitroassessment of platelet function in whole blood.Fibrinolysis is increasingly recognized as a pre-viously underestimated cause of perioperative bleed-ing [12, 29]. TE G may be a more sensitive test forfibrinolysis than routine tests, including D-D imers(fibrin degradation products) and euglobin clot lysistimes [37, 43]. It has been shown to be a usefulmethod to diagnose and guide treatment of intra-operative fibrinolysis [14, 34].In summary, TE G gives information about fibrin-olytic activity and platelet function which is notgenerally available from routine coagulation screens(fig. 3). It would seem, therefore, to be suited as amonitor in any type of surgery associated withhaemostatic defects, either pre-existing or acquired.Both liver and cardiac surgery are frequently com-plicated by coagulopathies: during liver transplan-tation, bleeding is often the result of hyper-fibrinolysis [27] and in cardiac surgery, perioperative


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THROMBELASTOGRAPHY 309

FIG. 3. Specific haemostatic defects produce characteristic TEGtraces. A = Normal trace. B = Haemophilia: marked prolongationof r and K times. Decreased alpha angle, c = Thrombocytopenia:Normal r and rK times, decreased MA (< 40 mm ). D =Fibrinolysis: CLI < 8 5% . E = Hypercoagulability: short r time,increased MA and steep clot formation rate.blood loss is thought to be related to the acquiredreversible defect in platelet function that followscardiopulmonary bypass [7]. It is in these two areasthat much of the recent work on the efficacy ofmonitoring coagulation with TEG has been under-taken. Liver SurgeryPatients presenting for liver surgery frequently havesevere derangements of coagulation and fibrinolyticsystems. In cirrhotic subjects there is typically adecreased concentration of all factors (except factorsI and VIII) because of malabsorption of substrateand defective hepatic synthetic function, thrombo-cytopenia caused by hypersplenism and defectiveplatelet function and a 15% incidence of primaryfibrinolysis [6].The risk of bleeding following liver biopsy orduring surgery cannot be evaluated easily fromroutine haemostatic tests [17]. In many patients it isthe qualitative function that is disturbed, and it iswell recognized that quantative blood coagulationvalues do not necessarily reflect in vivo tissue/bloodclotting [5].Liver transplantation

The procedure of orthotopic liver transplantation(OLT) exemplifies the difficulties of monitoring

coagulation when the haemostatic system is sub-jected to multiple and rapidly changing insults.Baseline coagulation is disturbed, the degree varyingwith the underlying disease processbeing worst inpatients with hepatocellular disease. In the anhepaticphase, no coagulation factors are produced andreduced clearance of inhibitors and activators in-crease susceptibility to a fibrinolysis. Massive bloodloss can result in a dilutional coagulopathy beingsuperimposed on a deranged clotting profile. Afterreperfusion of the grafted liver there is frequentlyfurther deterioration in coagulation (both clinicallyand on the TEG). Conventional coagulation tests donot substantially alter at this point and it is likely thatthis deterioration is primarily a functional or quali-tative problem caused, for example, by hypo thermia,acidosis and substances released from the donor liver[13].

Generally, after the newly grafted liver resumes itssynthetic function, coagulation returns towards nor-mal in 1-2 h after reperfusion. Ho wev er, with apoorly functioning graft the coagulopathy maycontinue, resulting in substantial and sometimesuncontrollable blood loss. In this setting, it is readilyapparent that routine coagulation screens are in-adequate to deal with the rapidly changing cir-cumstances (fig. 4).Kang and colleagues [16] pioneered the use ofthrombelastography to monitor coagulation duringOLT. Therapy is guided by the various TEGvariables: fresh frozen plasma 2-4 units is given ifthe " r " time exceeds 15 min, platelets 1 u/1 0 kg aregiven if the maximum amplitude (MA) is less than40 mm {even if the platelet count is normal) andcryoprecipitate 6-12 u is given for persistent poorclot formation (alpha angle < 40) with normal M A.Kang's group found that total red cell and freshfrozen transfusions decreased in the T E G mon itoredgroup and attributed this to improved coagulation asa result of more intensive monitoring.Fibrinolysis

Fibrinolysis is a major component of the hae-mostatic disorders that contribute to perioperativebleeding during hepatic surgery [27]. Patients un der-

B C D E F

FIG. 4. Typical sequence of TEG traces during orthotopic liver transplant (OLT). A = Baseline TE G : low in clottingfactors and platelets, B = A nhepatic + 10 min : fibrinolysis developing, c = Anh epatic+ 45 min: severe fibrinolysis.D = Reperfusion + 5 min: straight line TEGno clot formation. E = Reperfusion + 15 min: after tranexamic acid.F = Reperfusion + 30min: some spontaneous correction in coagulation. G = Reperfusion+ 90 min : additional FF Pand platelets given, H = Reperfusion +120 min: normal TEG apart from prolonged r time (International Normal-ized Ratio = 2.3).



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310 BRITISH JOURNAL OF ANAESTHESIAAf

FIG. 5. In vitro assessment of antifibrinolytic therapy. A = Severefibrinolysis in a patient undergoing OL T. B = Tranexamic acid invitro: dem onstrate s successful reversal of fibrinoly sis. c =Tranexamic acid 500 mg given in vivo.

FIG. 6. TE G " hypercoagulability " du ring the anhepatic phase ofOLT in a patient with primary biliary cirrhosis. A = TEG inanhepatic phase: hypercoagulable, short r time and abnormallywide MA . B = After repcrfusion of grafted liver: increased r timeand normal MA.

going hepatic resections may develop fibrinolysisbecause of activated factors released by extensiveliver resection that are not adequately cleared by theliver remnant or because of hepatic ischaemia frominterm ittent occlusion of hepatic blood flow. DuringOLT there is an imbalance between activators andinhibitors of the fibrinolytic system. In particular,increased concentrations of tissue-type plasmin-ogen activator (tPA) occur, peaking at the end of theanhepatic period and immediately after graft reper-fusion. At the same time, concentrations of inhibitors(plasminogen activator inhibitor (PAI) and alpha 2antiplasmin) are almost unrecorda ble, often resultingin "e xp los ive " fibrinolysis [4, 13].The degree of fibrinolysis that occurs during anyliver surgery, but specifically during OLT, correlatessignificantly with intraoperative blood loss [19, 27].Before the use of TE G , antifibrinolytic therapy was,to a large extent, empirical and the indications for itsuse were ill defined, as monitoring of fibrinolysis isgenerally inadequate. Measurement of the clot lysisindex (CL I) from the TE G gives useful informationabout fibrinolytic activity and serial traces enabletherapy to be monitored. This is of obvious im-portance as antifibrinolytic therapy used in-appropriately can have potentially disastrous conse-quences for the patient. In addition, TEG can be

used for in vitro assessment of the effects of anyantifibrinolytic therapy [14]. This technique offers aunique method to test coagulation therapy before itsadministration to the patient (fig. 5).Hyper coagulation

All the hepatic diseases that present for livertransplantation do not result in major coagulopathieswith clotting factor deficiencies and thrombo-cytopenia. Patients with primary hepatocellularcarcinomas and those with cholestatic disease(primary biliary cirrhosis and sclerosing cholangitis)often have only minimally deranged coagulationprofiles. Indeed, a proportion of patients with theseunderlying diagnoses may be hypercoagulable [10,26], as indeed are many patients with Budd-Chiarisyndrome.Hype rcoagulability is difficult to detect on routinecoagulation tests unless the platelet count or fibrino-gen concentration is increased markedly. It isdiagnosed readily with the TEG by the presence ofa short r time, a rapidly increasing and broad alphaangle and an MA that exceeds 70 mm. Diagnosis ofa hypercoagulable state prevents the unnecessaryand possibly dangerous use of clotting factor andplatelet support (fig. 6).Hypercoagulability has also been documented inpatients undergoing hepatic resections. In carefullyselected patients, administration of heparin 1000-3000 u may reverse TE G signs of hypercoagulabilityand potentially decrease the incidence of thromboticcomplications [10].One of the most serious complications of livertransplantation is vascular thrombosis, especially ofthe hepatic arterial anastomosis [36]. It is welldocumented that deficiencies in antithrombin IIIand protein C occur in a proportion of patients forsome days after transp lantation [8] and may create aprothrombotic state that contributes to the risk ofthrombosis. Detection of this hypercoagulable stateby regular thrombe lastography is obviously of majorclinical importance.

Cardiac SurgeryCardiopulmonary bypass (CPB) induces severalcomplex disturbances in the coagulation and fibri-nolytic systems. In particular, multiple qualitativedefects in platelet function have been reported,including decreased aggregation and adhesion, re-duced binding of fibrinogen and depletion of alphagranules [1 ,7]. Routine coagulation tests are unableto assess the major haemo static disturba nce resultingfrom CPBthat is, the alteration of the interactionbetween the coagulation rascad e and platelet surface,caused by altered platelet function. Coagulationfunction and heparin activity during CPB aremonitored routinely using activated clotting times(ACT). ACT, although rapid and easy to use,assesses coagulation only up to the time of initialfibrin formation and gives no information on pla-telet-fibrin interactions, clot retraction or clot lysis;CPB affects all these aspects of coagulation.Spiess and colleagues [35] recently assessed theusefulness of TEG as an indicator of post-bypasscoagulopathies. They found that TEG was a sig-



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T H R O M B E L A S T O G R A P H Y 311

FIG. 7. Characteristic changes in the T EG before (A) and after (B)cardiopulmonary bypass. The most significant difference betweenthe TEG before and after bypass is the change in the MA: thedegree of change varies, but in most cases there is a reduction inMA. A marked deterioration in MA is indicative of plateletdysfunction. The alpha angle also decreases, indicating reducedplatelet activity and fibfinogen concentrations. The r time isgenerally unchanged after bypass; a very important finding thatstresses that a deficiency in clotting factors is uncomm on, and tha tfresh frozen plasma is usually NO T required.

nificantly better predictor (87 % accuracy) of post-operative haemorrhage and need for reoperationthan either ACT (30% accuracy) or conventionalcoagulation tests (PT, PTT, platelet count andfibrinogen: 51 % accuracy).Ka ng and colleagues also have examined the use ofT E G monitoring in cardiac surgery [15]. In a groupof 34 patients undergoing routine CABG or valvereplacements, post-bypass bleeding was managed onthe basis of clinical judgem ent, con ventional clottingscreens, or both. On this basis, 92 % of the patientsreceived fresh frozen plasma (FFP) and 30% alsoreceived platelet transfusions. However, on re-viewing the TEG tracings in these same patients,there was no evidence to indicate the need for F FP inany patient, and 60% of the platelet transfusionswere unnecessary. Kang and colleagues concludedthat TE G-g uide d therapy would decrease the use ofempirical therapy and excessive transfusions (fig. 7).Platelet dysfunction an d aspirin therapy

Patients treated with low-dose aspirin therapy arewell known to have bleeding problems sometimes, asa result of the effects of aspirin on platelet function.Template bleeding time is the only routinely avail-able test that is available currently to assess plateletfunction, but this is not always practical for use inthe operating room. It would appear that the TE G isunable to demonstrate the platelet dysfunction thatmay result from low-dose aspirin therapy [3, 20, 25].This lack of effect on the TEG is not entirelysurprising, as platelet aggregation by thrombin isrelatively unaffected by aspirin and the TEG is notable to measure platelet adhesion/release actions.Similarly, investigators have had difficulty inter-preting TEG changes in patients with chronic renalfailure [31]. The failure to demonstrate a reductionin MA may be because the primary abnormality ofplatelet function is a result of impaired adhesion tothe vessel wall, rather than impairment of the

aggregation m echanism [2]. In contrast, the T E G isan extremely useful tool to evaluate agents that affectplatelet aggregation [33, 41].Coagulation changes during cardiopulmonary bypass

Monitoring of coagulation on bypass is com-plicated by heparinization and a blood sample at thisstage gives only a straight line TEG. Recent pilotstudies have shown that the TEG may be used tofollow coagulopathy development during bypass inthe fully heparinized patient, by adequately acti-vating blood samples with celite before adding themto the TEG [32]. Celite shortens coagulation timebecause it acts as a contact surface which activatesFactor XII and platelets and stimulates the reserveclotting ability of a blood sample. By mixing theblood in the A C T tube in the recommended mannerand then placing a sample in the TEG cup foranalysis, a complete TEG profile may be obtainedstarting with the r time which is equivalent to theACT time.Optimum therapeutic interventions

The possibility of in vitro assessments of theeffects of pharmacological management of coagul-ation [14] raises interesting possibilities with regardto the use of antifibrinolytic agents such as epsilon-aminocaproic acid, tranexamic acid and aprotinin.Where abnormalities such as fibrinolysis are demon -strated on the TE G during cardiopulmonary bypass,the efficacy of using a particular pharmacologicalagent can be assessed in vitro, before administering itto the patient. In the same way, dose regimens forindividual patients can be calculated, by using, forexample, in vitro titrations of increasing concen-trations of antifibrinolytic therapy [30].

Massive Blood Loss: Dilutional CoagulopathyAfter m ajor haem orrhage, the replacemen t of red cellloss with banked blood is known to create thepotential for dilutional coagulopathy, as old blood isdeficient in both active clotting factors and functionalplatelets. To deal with this potential problem, manycentres use procedures for replacement therapy thatare empirical and in some cases inappropriate. Newstudies have questioned the recommendations and,indeed, the need to use FFP supplementation orplatelet transfusions after massive transfusions in allpatients unless deficiencies are first demonstrated[22, 23, 38].Tuman and colleagues studied the effects ofprogressive blood loss on coagulation as measu red byTEG [40]. Analysis of the TEG demonstrated atrend towards increased coagulability with progress-ive blood loss, even thoug h losses were replaced onlywith crystalloid and packed red blood cells. It wasonly when blood losses exceeded 80% of theestimated blood volume that some patients began toshow clinical and TEG evidence of coagulopathy.The mechanisms that maintain or even enhancecoagulation during progressive blood loss are un-certain. It may well be that normal individuals havea "coagulation reserve" and that this, together withthe hormonal changes associated with surgery (in-creased concentrations of renin, angiotensin, cate-



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312 BRITISH JOURNAL OF ANAESTHESIAcholamines etc.), and the release of tissue throm-boplastin from tissue trauma offsets any tendency tohypocoagulation associated with haemodilution.The authors concluded that, in patients withoutfactors known to influence coagulation (underlyinghaematological disease, hepatic dysfunction, sepsisor hypothermia), there is no justification for theroutine use of FFP or platelet supplementationduring moderate to massive blood loss. Use of bloodproduct support has to be justified on haematologicaland clinical grounds, rather than on the basis ofempirical procedures [38].The varied response to massive normovolaemichaemodilution (blood loss exceeding 80% EBV)emp hasizes the need to monitor coagulation regularlythroughout surgery in such patients, in order thatplatelet and clotting factor support is given whenindicated on an individual basis, rather than ac-cording to a generalized format.

CONCLUSIONThere is still a "monitoring gap" in our ability toassess coagulation adequ ately in the operating theatreand a need to improve our management andunderstanding of haemostasis during the peri-operative period. There are many sophisticatedhaematological tests available to assist in the di-agnosis of haemostatic failure, but these are notgenerally available on an immediate or "on call"basis. In the operating theatre, faced with a bleedingpatient and perhaps complex and rapidly changingalterations in the haemostatic system, the anaes-thetist requires rapid and accurate information onwhich to base decisions for intervention.TEG offers a unique method of monitoringcoagulation that is practical for use in the operatingtheatre. It simplifies the diagnosis of coagulopathyduring operation by providing clinically relevantinformation and identifies changes for which therapyis available. Information about the whole clottingprocess is provided rapidly and can be monitoredserially. In addition, it may be used to determine theeffect of haemostatic drugs in vitro before admin-istration in the patient.The use of the TEG facilitates the early detectionof abnormalities in the haemostatic process andallows the anaesthetist to carry out remedial meas-ures with confidence before there is progression tosevere coagulopathy and uncontrolled blood loss.Accurate diagnosis of the current coagulation statusenables rationalization of the use of clotting factorsand platelet transfusions and eliminates the need forempirical therapy in patients undergoing surgery.

ACKNOWLEDGEMENTSWe thank Dr D . Royston and Mr B. Bidstrup for their advice andencouragement.

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