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TXA & Coagulopathy

Nicholas Macartney nick at macartney.org
Thu Dec 20 17:48:53 GMT 2012


We all have bad days.
To err is human, to forgive divine.
I liked the frankness - completely understandable.

Nick
Dr NJD Macartney FRCA FFICM
ICU Director
Chase Farm Hospital
The Ridgeway
Enfield
EN2 8JL
+4420 8375 1074

Delay in operating on non-elective patients is unacceptable ( NCEPOD 2011 )







On 20/12/2012 14:18, "Bjorn, Pret" <pbjorn at emh.org> wrote:

>THIS is the message I TRIED TO RECALL.  And then of course IMMEDIATELY
>after I recalled it, it finally squeezed through our firewall to the
>List.  Sh*t.
>
>Read it if you must; but please don't hold it against me.  Yesterday was
>a bad day.
>
>Pret
>
>-----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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