Best Practices For TBI Patients On Oral Anticoagulants: Part 5

Here is the fifth and final installment of my series summarizing the Austrian consensus paper on management of TBI patients with intracranial hemorrhage. The previous posts have run the gamut from diagnostic tests to detection of specific drugs to management. I’ve covered platelet inhibitors and Vitamin K antagonist reversal in previous posts, and today I’ll go over the panel’s reversal strategies for the direct oral anticoagulant drugs (DOACs).

Q1. Should idarucizumab (Praxbind) always be administered to patients with hemorrhagic TBI who are taking dabigatran (Pradaxa).

Answer: Only in cases where your laboratory is not capable of testing for thrombin time.

If thrombin time (TT) can be measured and is within the normal range, then the drug is not therapeutic and reversal should not be carried out. The consensus statement recommends giving this drug if the TT is prolonged or your lab cannot measure it. Keep in mind that there are very, very few papers on DOAC reversal in trauma patients. Most studies address the stroke population, and this may not translate well to trauma. And there are no studies yet that show that idarucizumab offers any survival benefit if given.

Q2. Should prothrombin complex concentrate (PCC) always be given to patients who are taking Factor Xa inhibitors?

Answer: Only in cases where your laboratory is not capable of testing for anti-Xa activity.

If anti-Xa activity can be measured (in a timely manner) and is low, then the drug is not therapeutic and PCC need not be given. If the level is high or your lab cannot test for it, then the group recommends administering PCC if the specific reversal agent (Andexxa) is not available.

As with dabigatran above, there is very little trauma literature to justify this recommendation. Furthermore, Andexxa is very expensive and, like idarucizumab, has not been shown to improve survival. Next week, I’ll write about why Andexxa is probably not worth the cost, in my opinion.

Q3. Should DOACs always be reversed in hemorrhagic TBI?

Answer: We don’t know.

As I just mentioned, there is little if any data showing that administration of a reversal agent is beneficial. And the decision to give it must be balanced with patient risk for thrombosis and consideration of any other agents they may be taking.  Expert opinion suggests that DOACs need not be reversed in TBI without blood on the CT scan, patients with unilateral, asymptomatic chronic subdural hematoma, and those with other wounds that do not appear to be bleeding excessively.

Hopefully, this series has helped shine some light on a confusing set of problems. Next week I’ll dig a bit deeper into the DOAC reversal agents Praxbind and Andexxa.

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 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.

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