Oliver,

Rotem (or TEG) surely can be used to monitor anticoagulation  in patients following liver transplantation.  The r-time on the ROTEM (or TEG) will denote the time taken for initiation of coagulation.  The rk-time denotes the time taken for clot formation; Angle denotes the kinetics of clot formation and MA denotes the strength of clot formation.  In an anticoagulant state the r-time will be prolonged and so is the rk time.  The angle is small and the MA is shorter than the baseline control value.  However, in a hypercoagulant state the r-time and rk-time will be much shorter than the control, the angle will be increased and the MA will also increase.  Following liver transplantation these parameters can be checked and based on the anticoagulation the TEG parameters will be altered to show patient's response to treatment.  Any shortening of the r-time despite anticoagulation will signify that the dosage may be increased.  Hence the patient's anticoagulant status can be monitored post liver transplantation.

Thanks so much for your answer. I do agree that is makes more sense to use these tests. However, in the latest guidelines (Monagle et al, Chest 2012), the target is the antiXa. Are you aware of any study using TEG or ROTEM as a target, and improving outcome?

Hi Oliver,

When it comes to monitoring of the potent anticoagulant drugs very highly sensitive techniques like TEG may not be helpful.  I am not aware of any clinical trials where this technique was used to monitor the anticoagulant drugs.  Although TEG can show a hypocoagulant effect by increased r-time and especially when the concentrations of the anticoagulant drugs are higher it just shows an indefinite increase in r-time and you may not be able to determine the level of anticoagulation.  Chromogenic tests like anti-Xa are used for monitoring low molecular weight heparins as you also found in the guidelines.

In my view the answer is a clear no.

ROTEM/TEG are excellent tests to guide treatement in acute trauma/bleeding and perioperatively. The are even some RCT published on that and more on the way.

There is little if no RCT data on anticoagulation and ROTEM/TEG. Possibly the problem is the signal to noise ratio. ROTEM/TEG mostly used as whole blood tests. In whole blood the hematocrit increases the signal to noise ratio. You can have a patient anticoagulated therapeutically on vitmain K antagonists or even heparin and not see it on ROTEM/TEG.

Anticoagulation in transplant patients rarely is an emergency decision. Time is sufficient to guide therapy by thrombin time, aPTT, antiFXa or the test of your choice. There are also some POCT devices emerging, which still need clinical validation. 

Hi Lars,

Thanks for your very interesting view on the signal to noise ratio. In your experience, what test should be used to assess the adequate anticoagulation? We have situations where the antiXa is 0.3 but the aPTT is 160. I know the target is supposed to be the antiXa, but my surgeons get a little stressed when they see such high aPTT values.

My interest in the TEG/ROTEM to target my anticoagulation is the impression that if the MCF is kept within the normal range, I can probably be a little more relaxed.

Hi Oliver.

You have outstanding coagulation experts in Geneva. They can explain the trouble of aPTT in heparin monitoring to you way better than I can.

My view is that aPTT in complex surgery (open heart, liver) is a bad test. The correlation aPTT and heparin concentration/effect is often not given in this context. Your example is perfect.

Next to aPTT you have thrombin time and antiFXa. I tend to use both of those tests to guide heparinisation in such surgery pts. Using two tests helps you prevent pitfalls of antiFXa and thrombin time which are rare but catastrophic if you miss them.

If you don't find help in the HUG, I can send you some powerpoint stuff on monitoring that might be of use.

Thanks Lars,

We are currently working with our experts in Geneva, such as Pierre Fontana, on a protocol to describe the ROTEM after liver transplant, in relation with individual coagulation factors and more global coagulation tests. I was wondering if anyone had some experience with the use of ROTEM to guide anticoagulation, as it would seem a good theoretical idea, if we could rely on more functional tests the aPTT, thrombin time and antiXa.

This discussion is interesting, because it reveals how little we know so far.

We have managed to get by with what are fairly blunt measures of anti-coagulation up to now but clearly there is a need for something more sophisticated. ROTEM sounds interesting but of course for us to be able to use it in clinical practice the test will need to be reliable, easy to perform and not too expensive (ie scalable).

Are you aware of the Transfusion Evidence Library Database which is the result of an initiative between BT NHS in the UK and Evidentia Publishing. The CEO of Evidentia Publishing is Mark Schregardus (who one can find via LinkedIn).

http://www.transfusionevidencelibrary.com

Hi Deborah,

Thanks for your answer. I will certainly search for information on this question in the Transfusion Evidence Library.

Hi Oliver

Here's a quick and dirty experiment, I did a few years ago to illustrate that aPTT was a bad test in situations with high FVIII concentrations (cardiac & transplant surgery):

(I had a nice graph, but the program doesn't allow for graphics, I can send it to you if you like)

I'll describe it:

- 0.35 IU/ml = therapeutic heparin concentrations were added to tubes with normal human plasma

- I prodcued tubes with 300% FVIII (by spiking normal human plasma with very small volumes of FVIII conentrate), 200%, 150% and 100%, ... I corrected for the volume with buffer where necessary etc

- I measured aPTT (ref range 3x ULN)

in other words the difference for 300% FVIII vs 100% (FVIII) was 60s% and this at identical heparin cocnentrations.

If you now consider that the 70s and  130s would have led you, as a transplant anestesiologist, to completely different management strategies. At 70s you would have left heparin perfusor at the same dose or increased it slightly. At 130s you would have reduced the dose. Again the heparin concentration was 0.35 IU in all samples, the only thing that was variable was FVIII... you may want to conclude that aPTT is not a good test in complex surgery.

Have Pierre do the experiment with a real sample of a transplant pt., the result will be the same (kind regards to him from Zurich)

Thanks so much for sharing this with me. It is really a great experiment! It really illustrates the difficulties with anticoagulation.

Omer is right, for this purpose the TEG should be replaced by specific chromogenic tests of F10a/F2a generation.