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TXA & Coagulopathy

Gross, Ronald Ronald.Gross at baystatehealth.org
Thu Dec 20 15:58:23 GMT 2012


It isn't that we never know how you feel anyway!!!!!
LOL


-----Original Message-----
From: trauma-list-bounces at trauma.org [mailto:trauma-list-bounces at trauma.org] On Behalf Of Pret Bjorn
Sent: Thursday, December 20, 2012 10:37 AM
To: 'Trauma-List [TRAUMA.ORG]'
Subject: RE: TXA & Coagulopathy

... and this was the one I tried to RECALL.  Fat lot of good THAT did.



-----Original Message-----
From: trauma-list-bounces at trauma.org [mailto:trauma-list-bounces at trauma.org]
On Behalf Of Bjorn, Pret
Sent: Wednesday, December 19, 2012 5:45 PM
To: Trauma-List [TRAUMA.ORG]
Subject: RE: TXA & Coagulopathy

Revisiting this thread, desperate for opinions more informed than my own.
(Meaning practically anyone's, but especially any of my friends intimate
with CRASH-2 and its offspring.)

I attended a local EMS leadership meeting here in Maine (USA) today, wherein
a colleague proposed administering TXA in the field for select cases (in
these parts, about one patient per day does not reach ANY hospital within
three hours of injury; and to date, precious few hospitals give the stuff
for trauma at all.

There was all manner of discouragement, including scoffing at the NNT, the
baseless yet ubiquitous and apparently indelible fear that  TXA risks harm
to patients with coagulopathy (or otherwise requiring clotting factors), and
so forth.  One of my closest friends announced, quite emphatically, that
"[her] surgeons aren't drinking the Kool Aid."  It was INFINITELY
depressing.

But specific to the use of TXA at my hospital (we are the ones running the
Kool Aid concession, apparently), there was especially harsh criticism for
our departure from the CRASH-2 dosing scheme.  See, at my hospital, we don't
drip.  Our experience is that this confuses and delays administration; and
moreover, it abandons (without any obvious reason we can see) half a century
of safe and effective (read: traditional) dosing.  We give 1.5 grams over 20
minutes to anyone under 60kg; and 2.0 grams over 20 minutes if they're 61 kg
and up.  Call us heretics.

And so, at the conclusion of the discussion, the final insult: "You're so
horny about CRASH-2, but you HAVE TO KNOW that without the DRIP, there is
ZERO assurance of efficacy!  It's COMPLETELY UNSCIENTIFIC!  You SILLY
BASTARDS!

(Okay, some of the words and emphasis are mine.  But trust me: the gist is
spot-on.)

Is there anyone out there who can talk to me about the 8-hour drip?  Either
convince me that it's important to the efficacy, or reassure me that we're
not silly bastards?  I'll take either one and be grateful.

Discuss!

(PLEASE!)

Pret


-----Original Message-----
From: trauma-list-bounces at trauma.org [mailto:trauma-list-bounces at trauma.org]
On Behalf Of Karim Brohi
Sent: Friday, November 02, 2012 5:55 PM
To: Trauma-List [TRAUMA.ORG]
Subject: Re: TXA & Coagulopathy

Juan

No one claims TXA to be a wonder drug.  In fact the claims are far less
exaggerated than those for high-dose plasma treatment.   Also no one is
suggesting that you *either* use TXA *or* you use high dose FFP, the two
approaches are clearly complimentary.

To try to answer your questions:

1. TXA (Tranexamic Acid) is an antifibrinolytic.  It inhibits plasmin which
itself lyses fibrin strands.  Plasmin is also a fibrinOGENolytic - ie it
breaks down fibrinogen, so TXA will also act to reduce any activee
fibrinOGENolysis.  The balance between these two is unknown.

2. We know that fibrinolysis activation is a hallmark of Acute Traumatic
Coagulopathy (ATC).  While only some patients show extreme hyperfibinolysis
to the extent it can be detected on TEG/ROTEM, all patients with ATC have
major fibrinolytic activation.  There is thus mechanistic rationale to
giving an antifibrinolytic.

3. We also know that fibrinogen levels are the first to fall in trauma as
you say.  Giving a drug that maintains fibrinogen (ie is
antifibrinogenolytic) - is therefore also mechanistically sensible.  (Note
that if you are (rightly) concerned about low fibrinogen levels, then giving
FFP up front is the wrong choice of component therapy - which is the
rationale for our current CRYOSTAT trial).

4. The absolute reduction in mortality in the CRASH2 trial was 1.5%.  This
as you say gives you a number needed to treat (NNT) of 67.  However you can
only apply the NNT to the specific trial population and its a stupid way of
assessing the efficacy of a therapy in *your* patient population.  For that
you need to know your population's baseline mortality risk and then apply
the relative reduction in mortality, which was 9.4% - and a 15% reduction in
the relative risk of bleeding.

5. The CRASH2 population had a relatively low mortality and by the inclusion
criteria included a large number of less severely injured patients.
(Predefined) subgroup analysis showed increased effect as the degree of
shock etc increased.  It is likely that your population where you apply DCR
is sicker and thus the effect of TXA would be greater (in absolute terms).

6. Great weight is put on the results of the MATTERS study which is a
retrospective study of military personnel requiring massive transfusion
treated with or without TXA.   They showed absolute risk reduction of 14%.
 However MATTERS actually compares outcomes for casualties treated in UK
bases which used TXA against those managed by US forces which did not.
 Many factors could also account for the improved survival in UK military
care, (especially use of MERT teams - see paper to be published soon).
 Ultimately both show the same effect.

7. If given early, TXA is safe.  This is data not just from CRASH2 but from
a wide range of RCTs evaluating the use of TXA

8. TXA is cheap.  It is cheaper and easier to give than lots and lots of FFP

9. You can't carry FFP in combat.  You can't get FFP in many parts of the
world.  You can't get red cells in many parts of the world.  Even if you can
you probably can't get it supplied consistently in a timely manner when you
need it.  You can give an iv dose of TXA.

10. You worry about who will benefit from it.  Clearly that is data we don't
know yet.  However it's likely to be a large proportion of the bleeding
population given its safety profile and the effect even in low-risk
populations.  I worry much much more about the exposure of patients to large
doses of FFP who may not need it - and this is as important an area for good
quality research

11. PROMMTT has reported - apart from the fact that its the most
incomprehensibly written paper in the history of the Journal of Trauma, tell
me it convinces you about the case for FFP and that we can't strive to do
better?

Karim




On Fri, Nov 2, 2012 at 9:15 PM, Duchesne, Juan C <jduchesn at tulane.edu>wrote:

> I agree with what Johnny published in Matters and I agree is a very
> unexpensive vitamin...... but my question is in a subset of severe
> hemorrhage patients resuscitated with effective DCR.....what is the
> benefit of adding TXA? In the sickest of the sick.....where is the
> evidence TXA actually improve my DCR mortality down from 30%.
>  We've demonstrated a reduction in mortality down from 30% in this
> subset of patients when inverse ratio of FFP to PRBC is used in
> combination with DCR down to 20% (JOT in press). Please provide me
> evidence where TXA will do the same in DCR patients resuscitated with
> 1:1:1:1 FFP:PLT:Cryo:PRBC in the presence of ACoTS.
> When I state: misunderstood wonder drug my concern is that a great
> potential drug might be misused just like we did with Factor VII
> (although like you well stated chipper) I believe there is a role for
> its use in DCR but what patients do actually will benefit from it?
> j
>
> On 11/2/12 4:02 PM, "Blueflightmedic" <trauma at emergencyunit.com> wrote:
>
> >The point of the studies is that they show, in real patients in a
> >wide variety of institutions around the world, an improvement in
> >outcome if tranexamic acid is administered soon after injury. The
> >CRASH-2 study is huge, and the data, with very robust statistical
analysis, shows benefit.
> >This is a pragmatic study in real patients in real trauma. My
> >personal experience (not really worth a bean in the context of this
> >data) is that patients seem to do better. Txa is NOT a substitute for
> >substrate, and I still give cryo as soon as possible, but the evidence is
clear - it helps.
> >Even better, it costs peanuts and has very few contraindications.
> >
> >You refer to a misunderstood wonder drug. Can you elaborate, please?
> >
> >-----Original Message-----
> >From: trauma-list-bounces at trauma.org
> >[mailto:trauma-list-bounces at trauma.org]
> >On Behalf Of Duchesne, Juan C
> >Sent: 02 November 2012 16:24
> >To: Trauma-List [TRAUMA.ORG]
> >Subject: Re: TXA & Coagulopathy
> >
> >Pret- I am so glad you brought up this question. I will like to know
> >the personal experience on big trauma centers with patients with
> >severe hemorrhage and TIC or ACoTS upon admission and outcomes using
> >TXA. In our institution I can say I AM NOT IMPRESS .
> >The NNT on previous studies was close if I am not mistaken to 67!!!
> >I am looking forward for someone to think out of the box and give me
> >a good reason to still use TXA in a patient with hyperfibrinolysis
> >with concomitant low serum fibrinogen levels. How is TXA going to
> >make a difference if there is no Fibrinogen inside the patient to
> >begin with? Why then just upfront load the patient with close ratio
> >fibrinogen instead of waiting for 67 patients to die in order to see
> >one live from this glorify misunderstood wonder drug? :>
> >
> >My 2 cents
> >
> >Duchesne
> >
> >On 11/2/12 11:13 AM, "Karim Brohi" <karimbrohi at gmail.com> wrote:
> >
> >>This has been sitting in my inbox for some time and I've been
> >>meaning to answer it - but surprised again at the conference
> >>yesterday how few people had heard of TXA, how many couldn't
> >>pronounce it, few knew how it worked (even/especially the doctors)
> >>and there remained a lot of confusion.
> >>
> >>Looks like we (I) need to do a much better job of communication
> >>around Trauma-Induced Coagulopathy and its management.
> >>
> >>Karim
> >>
> >>
> >>On Wed, Oct 10, 2012 at 12:19 AM, Ben Reynolds
> >><aneurysm_42 at yahoo.com>wrote:
> >>
> >>> Agree...few too many people know about / know how to use this drug...
> >>>
> >>> ________________________________
> >>>  From: "Bjorn, Pret" <pbjorn at emh.org>
> >>> To: 'Trauma-List [TRAUMA.ORG]' <trauma-list at trauma.org>
> >>> Sent: Tuesday, October 9, 2012 9:12 AM
> >>> Subject: TXA & Coagulopathy
> >>>
> >>> If this sounds like a stupid question, then for once, for me, it's
> >>> intentional:  What is the role of TXA in trauma with coagulopathy;
> >>>and what  are the implications of administering TXA simultaneously
> >>>with clotting  factors (i.e, PCC's)?
> >>>
> >>> I won't color the issue further, except to say that I'm sensing
> >>>widespread  confusion and trepidation, which I think are
> >>>discouraging the use of this  important drug.
> >>>
> >>> PLEASE talk this up.  I really want to learn more.
> >>>
> >>> Pret Bjorn, RN, etc.
> >>> Bangor, ME USA
> >>>
> >>>
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