Tag Archives: anticoagulation

Practice guidelines

Best Practices For TBI Patients On Oral Anticoagulants: Part 3

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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.

Practice guidelines

Best Practices For TBI Patients On Oral Anticoagulants: Part 1

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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.

Pharmacy

What Should We Call Them? NOAC vs DOAC

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They are the bane of trauma professionals, the anticoagulants that cannot be easily or cheaply reversed. Yes, I’m talking about the direct thrombin inhibitors and the Factor Xa inhibitors. They were originally called NOACs, or novel oral anticoagulants since they were newer than the old standard, warfarin. But they’ve also been listed as DOACs (direct) or TSOACS (target-specific, just rolls off the tongue doesn’t it?).

Here’s a nice table I put together recently showing the all the common oral agents available. Click the image for a full-size, more readable image.

Dabigatran was the first of the newer oral agents, and it is the only direct thrombin inhibitor in the group. The rest are Factor Xa inhibitors. This is easy to remember if you look at their generic name. Each will contain “xaban.” Get it? Xa ban.

The daily cost of warfarin is about $7, while the daily cost of the others is around $16 per day. However, that does not take into account the cost of blood work to monitor INR in those taking warfarin, so it’s cost will be higher.

What I found most interesting was the cost of the reversal agents, if any. For warfarin it’s either a hit of 4-factor prothrombin complex concentrate or many bags of plasma. Praxbind for the DTI dabigatran appears to be a bargain! But look at the agent for the Xa inhibitors, Andexxa! Almost $50K per pop!

And what about the asterisk, you ask? That means that there is no literature available that shows that these expensive drugs are clinically effective! But they seem like they should work. Hmm.

Anyway, back to the nomenclature. NOACs or DOACs? Opinion is moving away from NOAC because it can be misinterpreted as “no anticoagulants.” The International Society on Thrombosis and Haemostasis polled their members, and the consensus opinion was that DOAC should be adopted for common use.  They add that the specific mechanism of action (direct thrombin vs Xa inhibitor) should be specified in addition to the DOAC acronym when clinically relevant.

Bottom line: DOAC wins! So hopefully we can all converge on using one common term for this group of drugs. Yet I still shudder when I have a head injured patient that tells me they are taking any of them!

Reference: Recommendation on the nomenclature for oral anticoagulants: communication from the SSC of the ISTH.  J Thrombosis Haemostasis 13(6):1154-1156, 2015.

Pharmacy, Prevention

Anticoagulants And The Elderly: Are They Being Appropriately Treated?

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About 2.3 million people, or a bit less than 1% of the US population, have atrial fibrillation. This condition is commonly managed with anticoagulants to reduce the risk of stroke. Unfortunately, the elderly represent a large subset of those with a-fib. And the older we get, the more likely we are to fall. About half of those over 80 will fall once a year.

Are all of these elderly patients being treated with anticoagulants appropriately? Several scoring systems have been developed that allow us to predict the likelihood of ischemic stroke. Looking at it another way, they allow us to judge the appropriateness of using an anticoagulant to prevent such an event.

The original CHADS2 score was developed using retrospective Medicare data in the US. The newer CHA2DS2-VASC score used prospective data from multiple countries. However, the accuracy is about the same as the original CHADS2 score. But because the newer system has three more variables, it adds a few more people to the high-risk group who should receive an anticoagulant.

The higher the CHA2DS2-VASC score, the more likely one is to have an ischemic stroke. The threshold to justify anticoagulation seems to vary a bit, with some saying >1 and others going with >2. Here’s a chart that shows how the stroke risk increases.


Stroke risk per year with CHA2DS2-VASC score

Whereas CHA2DS2-VASC predicts the risk of clotting (ischemic stroke), the HAS-BLED score looks at the risk of bleeding. It includes clinical conditions, labile INR, and concomitant use of NSAIDs, aspirin or alcohol, but not a history of falls.

Proper management of atrial fibrillation in the elderly must carefully balance both of these risks to reduce potential harm as much as possible. A HAS-BLED score of >3 indicates a need to clinically review the risk-benefit ratio of anticoagulation. It does not provide an absolute threshold to stop it.

A group at Henry Ford Hospital in Detroit, a Level I trauma center, retrospectively reviewed their experience with patients who fell while taking an anticoagulant for atrial fibrillation. They calculated CHA2DS2-VASC and HAS-BLED for each and evaluated the appropriateness of their anticoagulation regimen.

Here are the factoids:

  • A total of 242 patients were reviewed, and the average age was 78
  • The average CHA2DS2-VASC score was 5, and the average HAS-BLED was 3
  • Only 1.6% were considered to be receiving an anticoagulant inappropriately (CHA2DS2-VASC 0 or 1)
  • Nearly 9% of patients were dead 30 days after the fall

Bottom line: The authors found that their population was appropriately anticoagulated. But they also noted that the morbidity and mortality risk was high, and was independent of age and comorbidities.

There are tools available to help us judge whether an elderly patient should be taking an anticoagulant for atrial fibrillation. The tool for predicting bleeding risk, however, is not as good for trauma patients. It ignores the added risk from falling, which is very common in the elderly.

Every patient admitted to the trauma service after a fall should have a critical assessment of their need for anticoagulation. The specific drug they are taking (reversible vs irreversible) should also be examined. If there is any question regarding appropriateness, the primary care provider should be contacted personally to discuss and modify their drug regimen. Don’t just rely on them reading the hospital discharge summary. Falls can be and are frequently fatal, just not immediately. Inappropriate use of anticoagulants can certainly contribute to this problem, so do your part to reduce that risk.

Related links and posts:

Reference: Falls, anticoagulation, and the elderly: are we inappropriately treating atrial fibrillation in this high-risk population? JACS 225(4S1):S53-S54, 2017.

General

EAST 2016: Lower Mortality In Patients Taking Newer Oral Anticoagulants vs Warfarin

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How not to write your abstract! The full title is this:

Trauma Patients on New Oral Anticoagulation Agents Have Lower Mortality Than Warfarin

Now let’s look at what it really says. This was a retrospective trauma registry review from a single Level I trauma center. Over a 14 month period, 275 of 1994 admitted patients were on anticoagulants.

Here are the (misleading) factoids and my comments:

  • Patients on warfarin had a higher mortality (13%) than those on new oral agents (NOA) (6%). (I can’t duplicate the statistical significance calculation)
  • Patients taking any anticoagulant were admitted to an ICU more often (44-50% vs 36%). (Duh! This just shows their usual practice, nothing new)
  • Patients on warfarin were more statistically likely to receive prothrombin complex concentrate. (Double duh! Because it doesn’t work for NOAs?)
  • The authors pointed out a trend toward more NOA use in this graph. (Really? It goes from 11 to 14 with wide monthly variations!)
image

Bottom line: This is why it’s so important to read the entire abstract and think about the stats. And ultimately, it’s even more important to read the whole paper! They don’t always say what you think they say!

Reference: Trauma patients on new oral anti-coagulation agents have lower mortality than those on warfarin. EAST 2016 Oral abstract #24.