Tag Archives: hemorrhage

Best Of EAST #16: More On TXA

Here’s another abstract dealing with TXA. But this one deals with the classic CRASH-2 use for patients with major bleeding. The original patient showed that TXA improves survival if given within 3 hours of injury. More and more prehospital units (particularly aeromedical services) have been administering TXA enroute to the trauma center to ensure that this drug is given as early as possible.

Many of these same services carry packed cells (or in rare cases, whole blood) so that proper resuscitation can be started while enroute as well. A multicenter group led by the University of Pittsburgh evaluated the utility of giving both TXA and blood during prehospital transport.

Their study summarizes some of the results of the Study of Tranexamic Acid During Air and Ground Medical Prehospital Transport Trial (STAAMP Trial). This study ran from 2015 to 2019 and randomized patients to receive either TXA or placebo during air or ground transport to a trauma center. It included blunt or penetrating patients at risk for hemorrhage within 2 hours of injury who were either hypotensive or tachycardic. Outcome measures included 30-day mortality, 24-hour mortality, and a host of complications.

This abstract outlines a secondary analysis that retrospectively reviewed the impact of using prehospital packed red cells (pRBC) in addition to the TXA/placebo during transport. 

Here are the factoids:

  • There were 763 patients in total, broken down as follows
    • TXA only – 350
    • pRBC only – 35
    • TXA + pRBC – 22
    • Neither – 356
  • Patients who received blood with or without TXA were more severely injured with ISS 22 vs 10-12 in the non-pRBC groups
  • Mortality was higher in the pRBC (23%) and TXA+pRBC groups (29%)
  • TXA alone did not decrease mortality
  • TXA + pRBC resulted in a 46% reduction in 30-day mortality but not at 24 hours
  • packed cells alone decreased 24-hour mortality by 47%

The authors concluded basically what was stated in the results: short term mortality was decreased by pRBC alone, and 30-day mortality with TXA + pRBC. They recommended further work to elucidate the mechanisms involved.

Bottom line: This abstract may also suffer from the “low numbers” syndrome I’ve written about so many times before. The conclusions are based on two small groups that make up only 7% of the entire study group. And these are the two groups with more than double the ISS of the rest of the patients. The authors used some sophisticated statistics to test their hypotheses, and they will need to explain how and why they are appropriate for this analysis. Nevertheless, the mortalities in the blood groups number only in the single digits, so I worry about these statistics.

Here are my questions for the authors and presenter:

  • How do you reconcile the significantly higher ISS in the two (very small) groups who got blood? How might this skew your conclusions regarding mortality? Couldn’t the TXA just be superfluous?
  • How confident are you with the statistical analysis? Could the results be a sampling error given that red cells were given to only 7% of the overall study group?
  • I am having a difficult time understanding the conclusion that mortality was reduced in the blood groups. Specifically, it is stated that 24-hour mortality is reduced by 47% in the blood-only group.  But the mortality is 14% (5 patients)! Reduced 47% from what? I don’t see any other numbers to compare with in the table. Confusing!

Obviously, there must be more information that was not listed in the abstract. Can’t wait to see it!

Reference: PREHOSPITAL SYNERGY: TRANEXAMIC ACID AND BLOOD TRANSFUSION IN PATIENTS AT RISK FOR HEMORRHAGE. EAST 35th ASA, oral abstract #39.

 

 

Reference: PREHOSPITAL SYNERGY: TRANEXAMIC ACID AND BLOOD TRANSFUSION IN PATIENTS AT RISK FOR HEMORRHAGE. EAST 35th ASA, oral abstract #39.

Life Threatening Bleeding In The Anticoagulated Patient – Part 3

Over the last two posts, I’ve explored some of the current definitions of “life-threatening bleeding” and shared my own take on a simplified yet more universal definition. So how can we put this into practice?

In the trauma world, we typically need to use this definition when dealing with patients who are taking anticoagulants. When a patient on this class of drug arrives at your center after trauma, they must be evaluated promptly. This is frequently in the form of a trauma activation, which provides rapid access to labs and imaging. If the patient does not meet activation criteria, some type of expedited response (limited activation or rapid evaluation by emergency physician) is required. The most important decision that must be made is, “does this patient need to have their anticoagulant reversed?”

This decision depends on the answers to the two criteria I laid out in the last post. Is either of these present?

  1. (Physiologic) Bleeding that causes hemodynamic compromise (hemorrhagic shock) or changes in vital signs indicating progression toward it (increasing pulse rate, decreasing blood pressure).
  2. (Anatomic) Bleeding into a body region or tissues that has a high likelihood of causing death, disability, or the need for operative intervention.

The first one is easy. Actual or developing hypovolemic shock should be obvious to any clinician managing the patient.

The second one is not necessarily as apparent. Although one may think that any intracranial blood may be life-threatening, sometimes it is not. What about a little subarachnoid hemorrhage? Or a tiny subdural in an area that typically does not progress?

So how to we determine if definition 2 is met? Phone a friend. Call an expert. There are so many potential areas for this type of bleeding to occur, a single emergency physician or other clinician may not be able to accurately make this judgment. So call your friendly, neighborhood neurosurgeon (head), or surgeon (abdomen, soft tissues), GI specialist (UGI bleed), or obstetrician (baby stuff). If they agree that it is life-threatening, the reverse the anticoagulant.

This level of oversight is important, because the reversal agents are not totally benign, or cheap. They have known complications, and one rare but important one is death. So make sure that their use is justified.

Final tips: Once you have determined that reversal is required, use the fastest agent(s) available. For warfarin, this means prothrombin complex concentrate (PCC) and not plasma. Typically, plasma reversal requires at least 4 units, and this takes hours. PCC takes 30 minutes or less. 

Document your judgment well, and your conversations with specialists who are helping you with definition #2. This is critical, because there have to be checks and balances for use of your rapid reversal protocols. There must be a post hoc analysis of each and every reversal, just like there should be for use of your massive transfusion protocol. A group of knowledgeable clinicians must review the clinical information that was available at the time of presentation, and render their agreement or disagreement to provide a good feedback loop and ensure proper usage of these products.

 

What Is: Life Threatening Bleeding In The Anticoagulated Patient – Part 2

In my last post, I showed you some of the current definitions of “life-threatening” bleeding used in patients who are anticoagulated, as well as some for lesser degrees of bleeding. Confusing, right? How are we to ever know what is truly life-threatening so we can justify intervention/reversal with potent and/or expensive drugs and blood products?

It’s time for a more universal definition. The most important thing to recognize up front is that it is absolutely impossible to provide a comprehensive set of definitions that take every possible scenario into account. The list would be confusingly long. We really only need a few rules that are a bit more generalized. But then, how do we keep providers from just doing what they want, and coming up with some subjective or anecdotal justification? Bear with me for a day or two.

Today, I’ll lay out my two “universal definitions” of significant bleeding in an anticoagulated patient. Note that I didn’t say “life-threatening” bleeding. There is also such a thing as “limb-threatening” or “tissue-threatening” bleeding, and yet other ways to be harmed from uncontrolled bleeding due to anticoagulants.

If you look through all the various criteria that I included in the last post, you can see that they generally fall into two categories: physiologic and anatomic. The key is to reach a balance of being specific enough without being overly so. This still allows for some degree of clinician judgment. But as you will see in my next post, there also has to be some type of scrutiny and review of that judgment.

So here is what I propose. Bleeding is considered significant and/or life-threatening if either of these are true:

  1. (Physiologic) Bleeding that causes hemodynamic compromise (hemorrhagic shock) or changes in vital signs indicating progression toward it (increasing pulse rate, decreasing blood pressure).

  2. (Anatomic) Bleeding into a body region or tissues that has a high likelihood of causing death, disability, or the need for operative intervention.

In my next post, I’ll show you how to operationalize these definitions into a workable process for making decisions about reversing anticoagulation.

 

What Is: Life Threatening Bleeding In The Anticoagulated Patient – Part 1

We are moving into a world where more and more people are taking anticoagulants. And as the number of possible anticoagulant drugs increases, the prospect of reversing them becomes more complicated. Just as the price of those medications continues to climb, so does the price of the agents used to reverse them.

The decision to reverse an anticoagulant, the speed of reversal, and choice of reversal agent all depend on an assessment of the severity of bleeding. Some reversal drugs such as prothrombin complex concentrate (PCC) act almost immediately but are expensive. Others take time, but are cheaper such as plasma and vitamin K.

Unfortunately, trying to come to a consensus on what constitutes life-threatening bleeding is very difficult. Over the years, numerous studies have been done, with almost as many definitions of bleeding. As you know, I am generally against reinventing the wheel. Borrowing someone else’s excellent work saves a lot of time and anguish.

But when it comes to defining dangerous bleeding, we are faced with so many definitions, it just begs for a “unifying theory.” I’ll show you some of the more commonly used definitions below. At the very bottom, I’ve included a link to a very comprehensive list of definitions that have been used.

First, there’s TIMI (Thrombolysis in Myocardial Infarction trial) and GUSTO (Global Use of Strategies to Open Occluded Arteries trial). (Please remember how much I dislike cute acronyms.)

The following consolidated definition was published in the Journal of Thrombosis and Haemostsis way back in 2005:

If you want to look at a more comprehensive list of a lot of definitions, download the document from the link below.

So how do we make sense of all this? As trauma professionals and clinicians on the front line of anticoagulant reversal, we need a simple definition. I’ve recently looked over as many definitions as I could lay my hands on. 

In my next post, I’ll propose a simplified set of definitions. And I’ll be very interested in your input and comments. They will ultimately end up as a definition that we will use at my own trauma center. And maybe yours.

Related post:

Reference:

  • Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. Journal of Thrombosis and Haemostasis, 3: 692–694, 2005.

How To Remember Those “Classes of Hemorrhage”

The Advanced Trauma Life Support course lists “classes of hemorrhage”, and various other sources list a similar classification for shock. I’ve not been able to pinpoint where these concepts came from, exactly. But I am sure of one thing: you will be tested on it at some point in your lifetime.

Here’s the table used by the ATLS course:

classes_of_shock

The question you will always be asked is:

What class of hemorrhage (or what % of blood volume loss) is the first to demonstrate systolic hypotension?

This is important because prehospital providers and those in the ED typically rely on systolic blood pressure to figure out if their patient is in trouble.

The answer is Class III, or 30-40%. But how do you remember the damn percentages?

multiscore-maxi1

It’s easy! The numbers are all tennis scores. Here’s how to remember them:

Class I up to 15% Love – 15
Class II 15-30% 15 – 30
Class III 30-40 30 – 40
Class IV >40% Game (almost) over!

Bottom line: Never miss that question again!