Prehospital plasma: Not a done deal just yet!

Our Society has pulled off what I have always wanted.  We have managed to have two intellectually satisfying editorials on a challenging subject, such as the prehospital administration of plasma.  Last month, Dr. Dante Yeh summarized and explained how the PAMPer study justifies the administration of plasma in the prehospital study.  It is a randomized control study with a positive mortality benefit.  It was also logistically complex to conduct, and so it is highly unlikely that any other study will be able to perform such a trial again.  However, if you thought the verdict was out, Dr. Kevin Blaine has written a response to Dr. Yeh editorial.  His powerful arguments have left me in a conundrum, “Should we be administering plasma in the prehospital setting?”  I am excited to see your responses after you read it for yourself.

Dr Blaine is a trauma anesthesiologist, intensivist, and Assistant Professor at the Keck School of Medicine of the University of Southern California. With a background in clinical trials, his current research interests include acute traumatic coagulopathy and next-generation coagulation tests.

Comments

  1. commenter img tasedit2 weeks ago

    Dear All,
    I carefully read the comment of Dr. Blaine regarding the PAMPer study. I agree with him that if prehospital plasma decreases mortality, it is unlikely due to a major shift of the coagulation status of these severely traumatized patients. Dr. Baine made important points:
    The INR is a poor test to evaluate the coagulation status of a trauma patient. Furthermore, the statistical difference (1.2 versus 1.3) is present because of the large number of patients.
    The mechanism of hypocoagulability is largely (not completely) due to the maladaptive activation of the Protein C. Although activated Protein C deactivates Factors V and VIII, the level of these activated factors in the plasma of these patients is above 30%. In a recent paper, Karim Brohi has shown that the major effect of the activated Protein C is an activation of the fibrinolysis at least in part secondary to the inhibition of PAI-1.
    Gene Moore’s group in Denver has raised the question whether a large number of trauma patients present with a fibrinolysis shutdown instead of a hypocoagulation (only 25-30% of the trauma patients are hypocagulable at admission to the hospital).
    So, is it possible that giving plasma (or other blood product) before admission to the hospital would decrease the duration of shock and that effect may be of critical importance. Furthermore, there are at least preliminary evidence that plasma might offer a protection for the endothelial glycocalyx that we know is damaged by a severe hemorrhagic shock.

    Warm regards,
    Jean-Francois Pittet

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  2. commenter img tasedit2 weeks ago

    Thanks, Kevin, for an interesting response. I agree that we should approach PAMPer results with caution. I’m very glad you covered the “maybe it helps but not because of clotting” territory, but I’ll add one more possibility there: Maybe plasma helps because it’s better for the endothelium than alternative volume expanders. Clotting is one piece of this equation, but there are others. Preservation of the glycocalyx, clinically translating as ‘permeability’, might be an important benefit of plasma vs. non-plasma resuscitation. And increased permeability in the brain (for example) might affect survival from TBI. Increased permeability in the gut might affect sepsis risk. Etc.

    This thought is similar to thinking around CRASH-2. TXA worked, but didn’t reduce measured blood loss or transfusion requirement. So the effect may relate more to anti-inflammation than to clot stabilization.

    One side note: NIH/FDA mandate 30-day survival as the primary endpoint for Exception from Informed Consent studies (or at least they used to), which constrained the study design here. I know this because I was a reviewer of the original grant. I probably told the investigators that they should be looking at 6 hour mortality – just goes to show how thinking changes!
    Rick Dutton

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