Tag Archives: TBI

Best Practices For TBI Patients On Oral Anticoagulants: Part 4

In my last post, I started reviewing the anticoagulant reversal section of the Austrian consensus statement on TBI patients taking anticoagulants. Due to its length, I covered only anti-platelet agents. Today I’ll discuss their findings on reversing  Vitamin K antagonists.

Q1. Should Vitamin K antagonists (VKAs) be reversed in case of hemorrhagic TBI?

Answer: That’s simple. Yes!

Q2. Should Vitamin K be administered to reverse the effects of VKAs?

Answer: Yes, as an adjunct to other reversal agents. The usual dose is 5-10mg IV.

Adjuncts must always be used, because Vitamin K only enables the liver to produce factors II, VII, IX, and X. This is not an immediate process, and may take up to 24 hours for the INR to fall to reasonable levels. Additional treatment is needed to raise these factor levels quickly.

Q3. Should prothrombin complex concentrate (PCC) and/or plasma be used for reversal of VKAs?

Answer: Four-factor PCC is the treatment of choice, and is preferred over plasma. 

Reversal of VKAs with plasma requires administration of large volumes, and each unit is given over one to two hours. This results in a slower correction when compared to PCC, which occurs in less than 30 minutes. And many elderly patients with comorbidities cannot tolerate the colloid volume administered with multiple units of plasma. Multiple studies have shown that patients treated with PCC achieve their target INR significantly faster and have less hematoma progression than those treated with plasma.

Q4. Should recombinant activated factor VII (rFVIIa) be used for reversal of VKAs?

Answer: No.

This drug was the darling in trauma care around the turn of the century, but has since fallen into disuse. The few studies available show that there may be INR rebound and more frequent hematoma expansion compared to PCC.

Next post: Recommendations for reversal of DOACs.

Reference: Diagnostic and therapeutic approach in adult patients with traumatic brain injury receiving oral anticoagulant therapy: an Austrian interdisciplinary consensus statement. Crit Care 23:62, 2019.

Best Practices For TBI Patients On Oral Anticoagulants: Part 3

My last post covered coagulation tests for oral anticoagulants and antiplatelet agents, as well as target levels of reversal. Today, I’ll share more of the Austrian consensus paper on actual reversal of anticoagulants. I’ll also add a little commentary to some of the answers.

This is a lengthy section in the paper, so I’ll split it into antiplatelet agents today, the vitamin K antagonists tomorrow, and the direct oral anticoagulants (DOACs) after that.

Q1. Should desmopressin (DDAVP) be administered to reverse the effect of platelet inhibitors?

Answer: No recommendation. (My answer: no)

DDAVP accelerates platelet adhesion. Very few papers have looked at using DDAVP in patients with platelet inhibition, and those that did had low numbers of subjects. The only positive study showed a reduction in hematoma of only 0.5 cc (in hemorrhagic stroke patients, by the way, not trauma). This is not clinically significant. It is likely that the nonfunctional platelets do not really respond to DDAVP, so this drug is not very useful.

Q2. Should TXA be used in patients receiving platelet inhibitors?

Answer: No recommendation. (My answer: no)

There are few, if any, studies that address this. A CRASH-2 subset with TBI showed no significant difference in intracranial hematoma size after TXA. Only one very small (80 patient) study showed a decreased total hematoma after TXA administration (2cc vs 4cc). I’m not sure how clinically significant this is. CRASH-3 did not address it. Overall there is too little data to make a decision regarding this one. It’s value, if any, is very subtle.

Q3. Should platelet concentrate be administered to reverse the effect of platelet inhibitors?

Answer: No

There are no studies that have shown any clear benefit to giving units of platelets to these patients. And a meta-analysis showed no survival benefit. Giving platelets sounds like a good idea, but remember that the drug that poisoned the patient’s platelets is still circulating. It can and does poison the new platelets as well. So adding more platelets that are destined to stop functioning doesn’t seem like a good idea.

In my next post, I’ll dig into the recommendations for reversing Vitamin K antagonists (warfarin).

Reference: Diagnostic and therapeutic approach in adult patients with traumatic brain injury receiving oral anticoagulant therapy: an Austrian interdisciplinary consensus statement. Crit Care 23:62, 2019.

Best Practices For TBI Patients On Oral Anticoagulants: Part 2

In my previous post, I reviewed recommendations from an Austrian consensus panel addressing patients with TBI on anticoagulants of various types. In this one, I’ll share their statements on coagulation tests and target levels for reversal of the different agents.

Q1. Are platelet function tests capable of detecting and/or ruling out the presence of a platelet inhibitor?

Answer: The three commonly used tests (PFA, Multiplate, and VerifyNow) can detect or rule out the presence of these drugs.

They can also determine whether the amount of platelet inhibition is within therapeutic range for the drug. But they cannot predict if someone with high inhibition will actually bleed, or if a patient with low inhibition will not. And knowing that they have a platelet inhibitor on board probably doesn’t help much because there is not much we can do to reverse them (see next post).

Q2. What is the goal INR after reversing Vitamin K antagonists?

Answer: The INR target value should be < 1.5

This recommendation is not supported by great data. We know that as INR rises above 2, the odds of bleeding in TBI increases by 2.6x. But we don’t now exactly how low it needs to be to ensure no more bleeding occurs. And this probably depends on what is actually bleeding. A subarachnoid hemorrhage probably wouldn’t bleed much at any reasonable INR. A subdural (torn bridging veins) is more likely to at lower INR values. And an epidural (middle meningeal artery laceration) remains at high risk at any INR.

Using related literature, the goal INR is all over the place. So choose a number somewhere around 1.5 and use it. And remember, 4-factor prothrombin complex concentrate (PCC) can bring the INR down below that level, but plasma cannot (see my post What’s The INR Of FFP?)

Q3. Should I use standard coagulation tests (PT, PTT) to detect or rule out direct oral anticoulants (DOACs)

Answer: No

Standard assays like PT and PTT are unreliable with these drugs.

Q4. What test can be used to rule out the direct thrombin inhibitor dabigatran?

Answer: A negative thrombin time (TT) rules out any residual dabigatran anticoagulation.

Of course, this assumes that you know the patient is taking it!

Q5. What test should be used to rule out Factor Xa inhibitors?

Answer: Measuring anti-Factor Xa levels can rule these agents out if calibrated to low molecular weight heparin or the particular -xaban in use.

The major problem is that this is a very specialized test and is not available at all hospitals or at all hours. And it takes some time to run. So the practical answer is really “none.”

In my next post, I’ll review the panel’s recommendations for actual reversal of the various anticoagulant medications.

Reference: Diagnostic and therapeutic approach in adult patients with traumatic brain injury receiving oral anticoagulant therapy: an Austrian interdisciplinary consensus statement. Crit Care 23:62, 2019.

Best Practices For TBI Patients On Oral Anticoagulants: Part 1

Over the past five years, there has been a tremendous increase in the number of patients presenting to hospitals with traumatic brain injury. The bulk of these injuries occur in the elderly, and a rapidly growing number of them are taking anticoagulants for management of their medical comorbidities. Although there is a growing body of literature addressing this issue, many practical questions remained unanswered. This is due to the lack of randomized controlled studies of the clinical problems involved. And given the ethical issues of obtaining consent for them, there likely never will be.

An interdisciplinary group of Austrian experts was convened last year to consider the most common questions asked about TBI and concomitant anticoagulant use. They reviewed the existing literature from 2007 to 2018 and combined it with their own expertise to construct some initial answers to those questions.

Over the course of my next few posts, I’ll dig into each of the questions and review their suggested answers. And remember, all these Q&A apply to patients with known/suspected TBI with known/suspected oral anticoagulant use.

Let’s start with some diagnosis questions.

Q1. Should head CT be performed in all patients with known or suspected TBI and suspected or known use of anticoagulants?

Answer: All patients with TBI and potential or known use of anticoagulants should undergo an initial screening CT scan of the head.

A number of systems that predict the utility of head CT already exist (e.g. Canadian head CT rules). However, they do not and cannot take into account the various permutations of drugs and other medical conditions that may influence coagulation status. Vitamin K antagonists (VKA) like warfarin have been clearly shown to increase mortality after TBI. Data involving the use of anti-platelet agents or direct oral anticoagulants (DOAC) are a bit less clear.

Q2. Should a repeat head CT scan be repeated in these patients, and if so, when?

Answer: Patients with intracranial hemorrhage on their initial scan should have a repeat within 6-24 hours, based on the location of the bleed.

The natural course of patients who have an identified intracranial hemorrhage is extremely unpredictable. For that reason, a repeat scan is suggested. However, there are no consistent data that would indicate when this should occur. Indications and potential for progression vary by type of bleed (subarachnoid, subdural, epidural, intraparenchymal). Thus, you must work with your neurosurgeons to arrive at a reasonable repeat interval, and it may be different for a high-risk location (epidural) vs one with low risk (subarachnoid).

Q3. Should a patient with an initial head CT that is negative be admitted for neurologic monitoring?

Answer: Patients taking only aspirin with GCS 15 and initially negative head CT may be discharged. All other patients should be admitted for at least 24 hours for neurologic monitoring as follows (q1 hr x 4 hrs, q2 hr x 8 hrs, q4 hr x 12 hrs). Repeat head CT is indicated if there is any deterioration in neurologic exam.

Multiple papers have described the occurrence of delayed intracranial hemorrhage in patients taking oral anticoagulants other than aspirin. Although some bleeds may develop days or weeks after the initial injury, the majority occur during the first 24 hours. Routine repeat head CT in this group of patients with an initially negative scan has not been found to be helpful.

Q4. What about patients with an initially negative head CT who cannot be examined neurologically (intubation, sedation, dementia)?

Answer: Unexaminable patients should undergo a repeat head CT within 6-24 hours based on the underlying risk factors for development of delayed hemorrhage.

There is no real literature on this topic, but this statement makes sense. Each center should pick a reasonable time interval and include it in their own practice guideline.

In my next post, I’ll review the panel’s recommendations on coagulation tests and target levels for reversal of the various classes of anticoagulants.

Reference: Diagnostic and therapeutic approach in adult patients with traumatic brain injury receiving oral anticoagulant therapy: an Austrian interdisciplinary consensus statement. Crit Care 23:62, 2019.

AAST 2019 #6: DOACs Part 3!

A little further down the direct oral anticoagulants (DOACs) rabbit hole please? The abstract reviewed in my last post suggested that elderly patients taking these agents actually do better than those on warfarin. So if that’s the case, do we need to be so attentive to getting followup CT scans on these patients to ensure that nothing new and unexpected is happening?

The trauma group at UCSF – East Bay performed a multi-center review of the experience at “multiple” Level I trauma centers over a three year period. They included anticoagulated patients with blunt trauma who had a negative initial head CT. Patients taking only an anti-platelet agent or a non-oral anticoagulant were excluded.  They analyzed the data for new, delayed intracranial hemorrhage, use of reversal agents, neurosurgical intervention, readmission, and death.

Here are the factoids:

  • A total of 739 records were studied: 409 on warfarin and 330 on a DOAC. Average age was 79, and half were male.
  • Repeat head CT was performed only half the time (!)
  • Delayed hemorrhage was noted in 4% of warfarin cases (9 of 224) and 2.5% of DOAC cases (4 of 159)
  • There were no interventions or deaths in the DOAC group with followup CT, or in those who did not have the repeat scan
  • There was 1 intervention in the warfarin group and two deaths attributed to TBI
  • Reversal agents were administered to 2% of DOAC patients and 14% of warfarin patients
  • The authors performed a regression analysis that showed the two strong associations with delayed hemorrhage were male sex and AIS head > 2 (!)

The authors concluded that this “largest study” suggests that DOACs “may” have a better safety profile compared to warfarin and repeat head CT is not indicated.

Now, hold on a minute!

Rule #1: No single published paper should ever change your practice. They need to be confirmed by other, hopefully better work.

Rule #2: No single abstract should make you even think about changing your practice! These are preliminary works that always need more detail, more effort, and a lot more thought. They are meant to telegraph what the authors are working on and to raise interesting questions from the audience. They should stimulate others to try to replicate and improve upon the work. In general, if something looks really good as an abstract, the next step is successful publication. This means that peers have reviewed the data and agree that it looks promising. But then it should take several years of work by the original authors and others to prove or refute the claims.

This study was small in the first place, and became smaller because half did not have repeat CT scans. The only statistically significant result was that we confirmed that the providers were not very good about getting followup scans. Just because they didn’t do it doesn’t mean it’s not indicated, especially given the nature of the data and the very small numbers.

I consider this another very small piece in the puzzle that suggests DOACs are not as evil as warfarin. There are several of these low power studies floating around right now. But we need to hunker down and really do a big study right so we can start to get a clearer picture of what we should do. For now, it’s best to treat all anticoagulants and anti-platelet agents as evil and err on the side of overtreating.

Here are my comments and questions for the presenter and authors:

  • Why was the followup head CT rate so poor? Was this a “however they like to do it” thing, was there a protocol, did the trauma centers just not believe that DOACs could be bad?
  • What were the guidelines for reversal? If the initial head CT was normal, why ever reverse? This suggests that participating centers could do whatever they wanted based on unspecified criteria.
  • Was the regression analysis helpful in any way? Being male and having a mild TBI seem rather nonspecific factors and wouldn’t help select patients for reversal or repeat scan.
  • Please provide more information on the warfarin intervention and deaths.
  • Isn’t the title of this abstract rather bold for the quality of the results presented?

I’m sure there will be some lively debate at the end of this presentation!

Reference: Repeat CT head scan is not indicated in trauma patients taking novel anticoagulation: a multi-institutional study. AAST 2019, Oral Abstract #66.