Viscoelastic tests of clotting function (TEG and ROTEM)

To the extreme distress of many candidates, the TEG had come up recently in Question 26 from the second paper of 2014, and again in Question 8 from the second paper of 2015. Then, the college really ground them down in Question 21 from the first paper of 2019, where they asked for a comparison of TEG with an empiric massive transfusion strategy.

The best summary to guide the time-poor candidate can be found (as always) at the Practical Haemostasis website. The LITFL TEG/ROTEM page is also an excellent balance between detail and brevity. The aim of this chapter is not to supercede these outstanding resources, but rather to act as a footnote for them, and to expand on key issues in a way which renders this complex topic easily understood by somebody who has not slept or eaten for some days.

For those with infinite time, the following resources exist at the Haemoview website:

Haemonetics also has a ton of TEG-related literature for their products:

Without further ado:

What the hell is TEG and ROTEM?

TEG is ThromboElastoGraphy, and ROTEM is ROtational ThromboElastoMetry, both acronyms being registered trademarks. Both are tools of assessing whole blood clotting. Whole blood (a miniute amoutn of it, no more than 1ml) at body temperature (37º) is added to a heated cuvette (a little cup). A pin is suspended into the cup, and then some sort of rotation takes place. In fact  the main difference between TEG and ROTEM is the bit which rotates (TEG rotates the cup, and ROTEM rotates the pin). Irrespective of which bit is rotating, some impediment to the rotation develops as the blood clots. The degree of this impediment is recorded as "amplitude", and displayed on the time vs. amplitude graph.

The TEG and ROTEM graphs, and differences in nomenclature

As one can see, the graph is essentially the same but some of the labels are different.

Indeed, the TEG and ROTEM measured variables have a lot of functional overlap, as well be discussed later; however the results produced by these two systems cannot be compared directly, and in any given situation the two tests may disagree enough that the different results prompt different reactions from the clinician.

A more precisely labelled diagram specific for ROTEM is also available, and can be viewed  at the Haemoview website (ROTEM parameters)

What is the point of using this thing?

Advantages:

  • Point of care test, rapid turn-around (around 10-20min)
  • Theoretically may decrease the use of blood products.
  • A convenient method of testing fibrinolysis, which no other test can do.
  • Discriminates between coagulopathy due to thrombocytopenia and coagulopathy due to low fibrinogen
  • The cost of one ROTEM test is similar to the cost of a full coags panel (APTT, PT, platelet count and fibrinogen level were priced at $81.91 by QLD Health in November 2012)
  • Arguably, the data derived from ROTEM is more useful at the bedside than those tests, and is available sooner (within 10-20 minutes)

Disadvantages:

  • You actually need a bit of training to use this thing properly.
  • If you want a true MA reading (i.e. maximum clot strength), you need to use a fresh "native" sample unmodified with any activators, and therefore it must be processed within three minutes.
  • Even citrated samples have maximum stability between 30 and 240 minutes.
  • Even when used properly, the precision is poor: LITFL quote UK NEQAS data, with coefficients of variance ranging from 7.1% to 39.9% for TEG and 7.0% to 83.6% for ROTEM.
  • The machine warms the blood to 37 degrees, which will not be reflective of the haemostatic pathology inside the hypothermic patient.
  • It needs to be recalibrated 2-3 times a day
  • It needs regular servicing
  • The consumables are expensive (on recent calculations, $80.10 AU per use)

Advantages and disadvantages of using these devices will one day appear in some sort of sadistic viva situation. In brief, one can say that there is no clear advantage to their use, as a recent (2011) meta-analysis could not make a firm recommendation in their favour. "There is currently weak evidence to support the use of TEG/ROTEM as a tool to guide transfusion in patients with severe bleeding", say Wikkelsoe et al. No impact was identified on mortality, amount of blood transfused, incidence of surgical reinterventions, time to extubation, or length of stay in hospital and intensive care unit. Overall, it remains an expensive plaything.

How much better is it than best-practice empirical transfusion?

This was the topic of Question 21 from the first paper of 2019. The examiners referred to TEG specifically in the question and throughout the answer, but it is clear that they were using the term interchangeably with ROTEM, and so in the discussion to follow TEG is also used as a surrogate for all forms of global testing for clotting function. Though the question asked specifically for a discussion of advantages and disadvantages, the college answer was formulated in a "critically evaluate" fashion which typically calls for a description of the rationale and supporting evidence  As such, some mutant combination of the two answer formats is offered here, as a compromise which satisfies the authors' unhealthy preoccupation with tabulated answers.

Rationale for TEG-guided massive transfusion

  • Scenarios which call for massive transfusion are diverse in aetiology (variceal bleed, postpartum haemorrhage, ruptured AAA, anticoagulant toxicity)
  • Diversity of aetiology produces a diversity of transfusion requirements
  • Ergo, transfusion should be individually tailored wherever possible 
  • Empirical replacement of whole-blood-like products may over-replace some products and under-replace others depending on the scenario
  • Individually tailored transfusion should therefore prevent wasteful use of blood products and increase the chances of correcting the coagulopathy
  • To tailor the transfusion process to an individual case requires the ability to monitor all aspects of clotting function including platelet function and fibrinolysis
  • TEG offers these capabilities in a single point of care test 
A comparison of TEG and empirical massive transfusion

Advantages of TEG

  • Rapid (10-20min)
  • Cheaper than wasting blood products
  • Conserves blood bank resources
  • Rapidly becoming more common
  • Tests fibrinolysis, which otherwise you cannot conveniently do
  • Individualised care: compensates for intercase variability of clotting factor consumption
  • Can be used to demonstrate that coagulopathy is fully corrected, as a means of promoting surgical management (i.e. excludes "medical bleeding")

Disadvantages of TEG

  • Not as rapid as empirical transfusion (wastes valuable minutes)
  • More expensive than coags if you incorporate the added recalibration and maintenance cost
  • Rare in smaller and regional centres
  • Assessment of fibrinolysis is often omitted in place of routinely giving (cheap, safe) tranexamic acid
  • Requires training to use and interpret
  • Precision is poor (UK NEQAS data)
  • Does not account for coagulopathy of hypothermia
  • Does not identify warfarin or most NOACs (Nielsen et al, 2013) - the findings are nonspecific (just long R time) 
  • TEG-guided algorithms do not enjoy widespread familiarity and are not universally accepted as valid

Advantages of fixed ratio massive transfusion

  • Rapidly available (time-limited by the thawing of FFP only)
  • Available almost everywhere
  • Easily protocolised, i.e. easy to order and thus it does not divert focus from managing the trauma 
  • Cost of products themselves is the only expense; i.e. maintenance cost for the blood bank staff and equipment is not purely for support of MTPs.
  • Widespread familiarity with the standard transfusion ratio
  • Does not interfere with the use of TEG (i.e. one may simply order the MTP pack while waiting for the TEG  sample to cook)

Disadvantages of fixed ratio massive transfusion

  • The exact ration (eg. 1:1:1) is still a matter of debate
  • The fixed ratio of products does not account for the possibility of fibrinolysis (sure, everybody gets tranexamic acid, but strictly speaking it is not part of the transfusion pack)
  • The practice of fixed ratio massive transfusion is non-diagnostic, i.e. unlike TEG it is not an investigation of clotting function but rather a management protocol which is implemented before results are available. It does not give you any information by itself.

Evidence which compares TEG-guided protocols with fixed ratio transfusion

  • "Systematic review (2014)" mentioned by the college examiners in their answer to Question 21 is probably Da Luz et al (2014), a descriptive systematic review which used relaxed criteria to drag-net 55 studies (12,489 patients). TEG appeared to uncover all sorts of coagulopathies which would not have been discovered by conventional testing (eg. hypercoagulability, hyperfibrinolysis, platelet dysfunction) which was an interesting finding. Of the total 55 studies, only three were rated as having a low risk of bias.
  • Hunt et al (2015), on TEG in trauma-induced coagulopathy performed a meta-analysis using different criteria (Cochrane) and also only found the same three 3 studies worth analysing. which turned this into a narrative review. Even with the risk of bias being low, there was not enough data to make a call on this. "This evidence strongly suggests that at present these tests should only be used for research", the authors concluded.
  • Wikkelsø et al (2017) reviewed all the data on TEG use and found 17 trials with a total of 1493 participants; this was more favourable:
    • Blood product use was demonstrably reduced
    • Transition to surgery was not affected
    • Mortality appeared to be lower in the TEG cohort as compared to historical controls (3.9% vs 7.4%) but it would be hard to attribute this to TEG use or to take it seriously in any other sense
    • Evidence was largely of a low quality, and most of it came from trials involving cardiac surgical patients
  • STATA trial mentioned by the college examiners in their answer to Question 21 is currently in progress at the University of Sao Paulo General Hospital;  interim analysis in 2015 demonstrated that the intervention group (TEG-guided) does not have any increase in their mortality or morbidity.
  • Gonzalez et al (2016) mentioned by the college examiners in their answer to Question 21 found an implausibly higher survival rate in their TEG group (19.6% vs. 36.4%) among a small cohort of trauma patients (n =111). Less plasma and platelet use was also noted, which is probably more objective and genuine.

Which is better, TEG or ROTEM?

The two commercially competing systems confuse the issue by using different nomenclature for the same thing (eg. CT instead of R). Both use whole blood (usually citrated and then replenished with calcium), but ROTEM also uses a bunch of tests which make use of unusual pro-and anticoagulant factors, making it impossible to compare the results of one system with the other. This makes it important to choose only one system, and to commit to it. So, which to choose?

There is little to discriminate between them in terms of "utility", as both systems offer a sophisticated assessment of clotting. LITFL mentions that ROTEM is theoretically more resistant to mechanical shock, which makes it more useful "in the clinical setting", implying that the cardiothoracic operating theatre and the ICU place the device at risk of constantly being nudged and kicked. Thus, if one were able to position the machine in a special place where it is not in the way of stampeding medical staff, the two modalities would have equal appeal?

Little evidence exists to guide decisionmaking on this issue. A good review by Sankarankutty et al (2012) compared the two systems in the management of trauma, and concluded that "differences in the activators utilized in each device limit the direct comparability". The authors identified 24 studies of TEG and ROTEM in trauma, all of which presented "considerable heterogeneity". The review is interesting because it contrasts the two systems in a pragmatic manner, i.e. "how is this going to change the management of patients?" Interesting features were discovered:

  • TEG is older technology. It was developed in the late 1940s. ROTEM is a modification (and perhaps an improvement) on the older methods, but that is not to say that TEG is outdated- the two systems have evolved in parallel, arriving at similar solutions independently like Old World and New World vultures. The manufacturer's propaganda pamphlet suggests that ROTEM is superior because it has a touchscreen, runs on "virus-resistant" Linux, requires less blood (0.3ml vs 1ml) and is largely automated, which are advantages of the specific machine rather than of the diagnostic method per se.
  • Decisionmaking will be influenced by the choice of device:
    • Transfusion algorithms based on ROTEM appear to frequently recommend cryoprecipitate
    • TEG-based algorithms appear to favour the use of FFP
  • In liver transplantation (Coakley et al, 2006), TEG and ROTEM transfusion algorithms tend to agree in everything except the decision to give FFP (they were in agreement regarding platelet transfusion and cryoprecipitate).
  • In cardiac surgery (Venema et al, 2010) the two machines could not seem to agree regarding their R and K variables (CT and CFT for ROTEM), with the MA (MF) and  alpha-angle being the only consistent parameter, or at least "sufficient for clinical purposes". Changes in FFP requirements would again be the result: TEG users would use more FFP (TEG R times were consistently longer than INTEM and EXTEM CT values)
  • In trauma (Nielsen, 2007) the ROTEM system seems to have shorter reaction times, steeper angles and higher maximum amplitude, resulting in the impression that the patient is less coagulopathic. A reduced use of all blood products may be the consequence of this. The authors also commented that the use of celite to activate plasma reduced this variation.
  • There is regional (cultural?) variation in the distribution of these two devices. American centres prefer to use the American-owned TEG system, whereas the Europeans use the German ROTEM machines. In Australia, there is no firm preference. The college seems to prefer ROTEM (as they offered ROTEM graphics for interpretation in Question 26 from the second paper of 2014) and therefore this summary chapter will focus on ROTEM interpretation, and will use ROTEM terminology. A Queensland Health publication from 2012  reports that the Australian ROTEM distributor (Haemoview Diagnostics Pty Ltd) had counted 14 ROTEM machines and about 40-45 TEGs around Australia. The worldwide penetration of this technology apparently consists of 3000 ROTEM machines distributed across 1600 sites in over 50 countries.

The reaction times: CT and R values

The TEG uses "R" and ROTEM uses "CT" to describe the time it takes for the amplitude to start climbing. Arbitrarily, the 2mm point is used as a marker that the clotting cascade has started. This time vaguely relates to the time it takes for the enzymes of the clotting cascade to run their full course and ultimately arrive at the formation of fibrin from fibrinogen. The CT is therefore analogous to the old-school "clotting time" parameter used in the laboratories of yesteryear. The main influence on CT

Causes of prolonged CT and R-value

  • Anything that causes a raised PT and APTT:
    • Deficiency of clotting factors
    • Heparin (very sensitive - prolonged by 0.15 units per ml of blood, or a systemic heparin dose of less than 750 units for a 70kg adult)
    • Warfarin
  • Direct thrombin inhibitors

The reaction to a prolonged CT could consist of the administration of replacement factors (eg. FFP or factor concentrates) or antagonists to anticoagulants (eg. protamine).

Clot formation time (CFT)

ROTEM uses CFT and TEG uses the K value to describe the time from clot initiation (when the amplitude gets to 2mm) to 20mm. The CFT and K also relate to the activity of the clotting factors, but also incorporates a measure of the effectiveness of fibrin polymerisation, platelet activity and Factor XIII activity. In states of extreme coagulopathy, the clot may never actually form and the CFT will not be reported.

Causes of prolonged CFT

  • Thrombocytopenia
  • Platelet dysfunction
  • Low fibrinogen
  • Severe deficiency of other factors

Causes of Shortened CFT

  • Hypercoaguable states

The reaction to a prolonged CFT might sensibly consist of platelet transfusion, or cryoprecipitate.

The α-angle

For the α-angle, TEG uses the slope of a line connecting the point at which the R interval ends and the point at which the K interval ends. ROTEM, in contrast, uses the slope of the line at the 2mm amplitude mark. In either case, the slope is determined by the rate of reaction between platelets, fibrin and the clotting cascade factors. It is therefore probably a nonspecific variable. However, the manufacturer of the device insists that fibrinogen activity plays the greatest role in determining the α-angle.

Causes of a decreased α-angle

  • Low fibrinogen
  • Poor fibrinogen polymerisation
  • Thrombocytopenia, or platelet dysfunction

The reaction to a decreased α-angle might sensibly consist of cryoprecipitate transfusion, or of fibrinogen concentrate (where available).

Maximum clot firmness (MCF) and maximum amplitude (MA)

Both the TEG and ROTEM terms refer to the point at which the clot is at its thickest, causing the greatest amount of impediment to the cup-pin movement. This variable is primarily a measure of platelet count, platelet function and fibrinogen concentration. The MA on the TEG has to be performed on a clean native sample with no activator,  or from the combined Tissue Factor/kaolin activated TEG. There is a strong linear correlation between the log platelet count and MA.

The reaction to a decreased MCF is usually to either give platelets or DDAVP. However, clot instability may be also be the consequence of excessive fibrinolysis, which would manifest in the A60 or the LI30 indices.

Time to maximum amplitude (TMA or MCF-t)

Both the TEG and ROTEM terms refer to the time it takes to reach MCF or MA. Again, a complex system is involved, and a breakdown at any stage will prolong the time to maximum clot strength. At its crudest, this measurement should give you some idea as to how long you will need to keep pressure on the groin wound after you remove the IABP.

Amplitude at a specific time: A10, A30, A60

These markers can be arbitrarily placed anywhere. Conceivably, one might have an A3.15, or A240. The Haemoview literature as well as Question 26 from the second paper of 2014 both use A10. This is another marker of clot stability, and can be used instead of MCF in situations where the measurementof MCF is impractical (eg. when the patient is so ridiculously coagulopathic or anticoagulated that one might take all day to reach maximum clot stability).

The A10 therefore - like the MCF - is a surrogate marker of platelet function, platelet numbers, and fibrin concentration.

A decreased A10 can result from

  • low fibrinogen
  • thrombocytopenia
  • platelet aggregation inhibitors, eg.antiplateelt drugs

Clot Elasticity: G (TEG) or MCE (ROTEM)

This variable is infrequently reported, and there is little literature out there to explain exactly what this is. The maximum clot elasticity (MCE) is calculated from the MCF:

MCE = E=100 × MCF/(100-A)

Clot Lysis at a specific time (CL30, CL60 etc)

Instead of waiting for an inordinately long time for your result, it is possible to extrapolate the rate of fibrinolysis from the change in clot density over the half-hour that follows MCF(MA). One can then compare the 30 minute amplitude to the MCF as a fraction.

Time to lysis (LOT and CLT)

Ideally, this would be "time to complete lysis", or 98% lysis,  but we don't have all day, and so some surrogate measure must exist. The TEG  defines the term CLT as 2mm from MA, i.e. the time it takes for the clot to soften enough for the amplitude to decrease by 2mm from its maximum. The ROTEM term LOT (Lysis Onset Time) refers to the time it takes for the amplitude to drop by a 15% difference from the MCF, which is a slightly different parameter. Other machines have slightly different nomenclature again. In essence, an abnormally short time to lysis would suggest some sort of fibrinolysis is taking place.

The reaction to a decreased CLF is usually to give tranexamic acid or (in the old days) aprotinin.

References

Practical haemostasis - page on TEG and ROTEM

LITFL - Thromboelastogram

Sankarankutty, Ajith, et al. "TEG® and ROTEM® in trauma: similar test but different results." World J Emerg Surg 7.Suppl 1 (2012): S3.

Coakley, Margaret, et al. "Transfusion triggers in orthotopic liver transplantation: a comparison of the thromboelastometry analyzer, the thromboelastogram, and conventional coagulation tests." Journal of cardiothoracic and vascular anesthesia 20.4 (2006): 548-553.

Venema, Lieneke F., et al. "An assessment of clinical interchangeability of TEG® and ROTEM® thromboelastographic variables in cardiac surgical patients." Anesthesia & Analgesia 111.2 (2010): 339-344.

Nielsen, Vance G. "A comparison of the Thrombelastograph and the ROTEM." Blood Coagulation & Fibrinolysis 18.3 (2007): 247-252.

Wikkelsoe, A. J., et al. "Monitoring patients at risk of massive transfusion with Thrombelastography or Thromboelastometry: a systematic review." Acta Anaesthesiologica Scandinavica 55.10 (2011): 1174-1189.

Hunt, Harriet, et al. "Thromboelastography (TEG) and rotational thromboelastometry (ROTEM) for trauma‑induced coagulopathy in adult trauma patients with bleeding." Cochrane Database of Systematic Reviews 2 (2015).

Nielsen, Jorn Dalsgaard, and Galloway Gregg. "Monitoring novel anticoagulants dabigatran, rivaroxaban and apixaban by thrombelastography. Proof of concept." (2013): 4813-4813.

Wikkelsø, A., et al. "Thromboelastography (TEG) or rotational thromboelastometry (ROTEM) to monitor haemostatic treatment in bleeding patients: a systematic review with meta‐analysis and trial sequential analysis." Anaesthesia 72.4 (2017): 519-531.

Gonzalez, Eduardo, et al. "Goal-directed hemostatic resuscitation of trauma-induced coagulopathy: a pragmatic randomized clinical trial comparing a viscoelastic assay to conventional coagulation assays." Annals of surgery 263.6 (2016): 1051.

Da Luz, Luis Teodoro, et al. "Effect of thromboelastography (TEG®) and rotational thromboelastometry (ROTEM®) on diagnosis of coagulopathy, transfusion guidance and mortality in trauma: descriptive systematic review." Critical Care 18.5 (2014): 518.