When randomizing patients to two different plasma transfusion strategies, it is important to make sure the coagulation test used to differenciate both groups makes clinical sense.
Would you use INR (not designed for non-AVK patients but very commonly used), TP or aPTT ratios (more complicated to use are different tests yield different results), or ROTEM or TEG (not evaluated outside the massively-bleeding patients, and not often available)?
I would certainly use ROTEM/TEG as they provide information on the total coagulation status in the patient instead of selected clotting factors as in INR. In addition these test will get you the fastest answer. Laboratory tests should, however, always be interpreted based on the individual clinical situation of the patient.
As a Trauma Surgeon there are ample data that support the early administration of plasma and platelets for the critically injured trauma patient. This may not be relevant to the critically ill medicine patients.
Sadly none of the instruments/laboratory assays provide an adequate real-time picture of the patient's coagulation status. Even from TEG and ROTEM have issues related to patients with depleted fibrinogen stores and more importantly cold patients. Many critical care physicians failed to recognize that when a battery of coagulation tests are drawn and sent to the laboratory the laboratory warms the sample to 37°C. Trauma patients owe as much as 50% of the coagulopathy to hypothermia.
Consequently, the answer is clinical judgment. As a clinician you must take into account the injuries with their estimated blood loss and the patient's temperature and premorbid complicating medical conditions to determine when to give plasma. As a rule sooner is better than later and warmed is better than cold.
On a separate note we are currently using type A plasma in addition to AB plasma. The safety of this has now been documented but originally stems from the use of uncrossed matched platelets which carry with them a significant plasma store. I'm curious how many facilities have liberalize their use of type A plasma to expand the store of fresh plasma for their trauma patients?
Respectfully
John
Thanks so much for your great answers! They are going to be really useful!
A few weeks ago, the NIH State of the Science meeting recognized that the INR was unfortunately the "least worse" test that should be used, as the TEG/ROTEM are not widely available (only a quarter of the PICUs worldwide have access to such a device) and the results between the different device generations are not comparable. Furthermore, no one really knows if these tests capture the risk of bleeding in non-massively bleeding patients.
Regarding the clinical outcome, RBC transfusion requirements does make a lot of sense. However, one might also argue that RBC transfusions are not that bad (mortality was not increased in the liberal group of the TRIPICU study) and that it might be more important to measure global morbidity outcomes, such as organ failure, length of stay, ventilator-free days, etc.
Therefore, once again, I really appreciate your answers. They will help us design this trial!
Kind regards,
Oliver
John,
I'm sorry I can't really comment on your question regarding type A plasma. The Swiss medical authorities only allow for "iso-group" plasma transfusions... We do not have pre-thawed plasma either.
Your comment on temperature is also very valuable! Even though it might not be very common in PICUs, hypothermia is certainly a very important factor to consider! Thanks again!
The INR of plasma is 1.4 to 1.5. Giving plasma with the INR in that range is worthless. With the help of our hematologists we developed a protocol for cardiac surgery patients in which we give 1 unit for an INR of 1.5 -2.0, 2 units if the INR is 2.0-2.5 and 3 units if the INR is over 3.0. For higher INR we give Prothrombin Complex concentrates because of the volume issue with additional plasma. There is some good data related to INR elevation and degree of factor deficiency which supports the above protocol. We've found the use of TEG and ROTEM is also worthless. Our senior hematologist says that no in vitro test can predict in vivo coagulation any better than our regular coag tests and they have their limitations as well. We do not have a TEG or Rotem in our institution. Several published papers recently support this and the Society of Cardiac Anesthesiologists had a panel discussion at this year's meeting on TEG and Rotem and essentially said the same. We should not be basing any clinical decisions on the results of a these tests.
Dear Olivier.
Prothrombin time/INR is a coagulation test useful to monitor anticoagulation in patients treated with vitamin K antagoniosts. (see paper by Thorsten Haas in BJA 2014)
In the perioperative setting it is not predictive of bleeding. In the peritraumatic setting one of its few evidence based uses is to prove futility of FVIIa use in case it is too perturbed.
There are meta analyses quetsioning the rationale for FFP use. Some data even suggest that FFP may increase mortality - this is debatable. (see papers by Kozek Langenecker, Critical Care 2011 and Chowdhury BJH 2004)
Outside the context of FV deficiency, acquired or congenital, some experts may content that there actually is no valid FFP indication.
If you want to do an FFP study, I would consider including a negative control arm. If FFP indeed is harmful, this would eb the occasion to show that.
Just some thought provoking brain food
Kind regards,
Lars
Hi Lars,
Thanks so much for these great thoughts. Indeed, the INR is not designed to monitor anything else that AVK drugs. However, the NIH meeting on plasma transfusions has recommended its use, as the "least worst" test... This is partly because most tests now have an ISI close to 1.0. The INR results would therefore be very similar to a TP ratio.
Thanks also for your comment on the RCT. We do plan to have a negative control arm, within a certain INR range, to assess the negative effects of Plasma transfusions. However, although compelling observational data, no RCT has really demonstrated increased morbidity in the TRIPICU nor in the Age of Blood studies. Therefore, I'm not sure we will find anything... But we'll try hard!
Oliver
When you say no RCT has demonstrated increased morbidity for FFP, show me the RCT showing FFP safety or non-harmfulness...
We mutually agree that any RCT adressing the questions regarding FFP use in the ICU context is highly welcomed!
Lars
PS: the slide from this year's Coalat meeting (Villars sur Ollon, 5-7 March, 2015; talk on "Facteurs de coagulation en 2015") serves to illustrate that FFP does not have much RCT evidence in favor (green) but quite a lot against (red) according to the systematic review I cited before.
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