EMCrit Podcast 17 – Reversal of Anti-coagulant and Anti-platelet Drugs in Head Bleeds

liver factors in oat

So you have a patient with intracranial bleeding or you have a high pre-ct suspicion of intracranial bleeding and they are taking coumadin, aspirin, or clopidogrel. Should you reverse them? If so, how?

What if the CT is negative? Can you just discharge these patients as soon as they have a negative CT?

In this episode of the EMCrit Podcast, I discuss reversal of anti-coagulant drugs & anti-platelet medications, with particular emphasis on the prothrombin complex concentrates (PCC). I also touch on how to disposition these patients if their initial CT scan is negative.

Reversal Meds

Here are sample guidelines for drug reversal:

Warfarin
Any patient with a history of recent warfarin use, with an INR > 1.5 should immediately receive:
1. Vitamin K 10 mg IVPB over 10 minutes (monitor for hypotension / anaphylaxis) &
2. 50 units/kg of Prothrombin Complex Concentrate (Bebulin or Profilnine) Administer over 20 minutes.
• If PCC unavailable, give 15 cc/kg of FFP
Repeat INR 10 minutes after completion of infusion

Liver failure with known coagulopathy or elevated PT or INR •1.5
1. Vitamin K 10 mg IV over 10 minutes (monitor for hypotension / anaphylaxis) &
2. 50 units/kg of Prothrombin Complex Concentrate (Bebulin or Profilnine) &
3. 2 units of FFP
• If PCC unavailable, give 15 cc/kg of FFP total

Reversal of Platelet Dysfunction: For any patient with antiplatelet (Aspirin, Aggrenox or Clopidogrel) used in last 24 hours administer:
1. dDAVP 0.3 mcg/kg x 1 (20 mcg in 50 cc NS over 15-30 minutes) &
2. 1 donor pack platelets (~6 units)

Review Article of Vitamin K antagonist reversal (Critical Care 2009, 13:209)

Review Article on PCCs (European Journal of Anaesthesiology 2008; 25: 784–789)

CT Negative after Head Trauma while on Anti-coagulants or Anti-plt Meds

One man’s jury-rigged approach:

Minor head trauma (the definition of this in the anticoagulant literature seems to be different than most other head trauma lit, they actually define minor as NO LOC and NO AMNESIA, just a bop to the head)

  • Most folks would still say scan these patients once and then observe for 6 hours. A few would say just observe, a very few would say admit for 24 hours. I watch them for 6 hours and then get the CT scan.

Head trauma with LOC, but GCS 15

  • definitely scan, definitely observe at least 6 hours, most would say either rescan or admit for 24 hours

Head trauma with LOC, but GCS < 15

  • scan, almost certainly admit for 24 hours, probably rescan prior to d/c

Not great literature support for any of this, here are some studies to get you started:

Delayed Posttraumatic Acute Subdural Hematoma in Elderly Patients on Anticoagulation (Neurosurgery 58:851-856, 2006)

Low Dose ASA led to secondary bleeding not seen on initial CT in patients with normal neuro exams (J Trauma 2009 67(3):521)

Update:

From EM:RAP Aug 2013

Nishijima DK et al. Immediate and delayed traumatic intracranial hemorrhage in patients with head trauma and preinjury
warfarin or clopidogrel use. Ann Emerg Med. 2012 Jun;59(6):460-8.
o A prospective, observational study at 2 trauma centers and 4 community hospitals. Most of these patients were community
hospital patients. They included patients with blunt head trauma who were using warfarin or Plavix. The patients were
followed for two weeks. They looked at what percentage of the patients had head bleeds and delayed head bleeds.
o 1,064 patients were enrolled (72% were on warfarin and 28% on Plavix). The prevalence of immediate traumatic intracranial
hemorrhage was higher in patients on Plavix than warfarin (12% versus 5%). This is high enough to recommend the use of
CT head in patients on these medications with trauma. A significant number of these patients had minor trauma, normal neuro
exam, no loss of consciousness and no evidence of trauma (11% with warfarin

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Comments

  1. This is a great talk. It’s funny because I’ve mentioned delayed bleeding in the past to admitting teams and they are usually unaware of this possibility. It definitely makes me think twice about sending these patients home at least without delayed observation in the ED.

    • Faheem, thanks for commenting. It’s funny that the literature emerges from Neurosurgery and Trauma, and yet they are the services often most reluctant to admit.

  2. We use Factor 7 for head bleeds in patients on warfarin. Should we be using the three-factor PCC along with this? (We have Beriplex (four-factor PCC) at our institution as a study drug, so I’ve seen it in action. I’m looking forward to using it when it’s approved in this country).

    • Jeremy,

      Not a huge fan of factor VIIa for head bleeds as it wears off quickly so the patient is back to anti-coag state and it makes the INR a lie, so you don’t know how effective your reversal. We use 3-factor exclusively and have gotten most of our patient’s reversed. The beriplex would be the ideal, so if you can get access that is what I would use.

      Scott

  3. Great talk.
    We increasingly use PCC for anticoagulant associated head bleeds with good results. Factor VII would be a good option for patients needing emergent neurosurgical procedures such as an EVD placement. The combination of PCC and Factor VII would amplify the risk of thrombosis in a trauma patient with questionable benefit.
    For Anti-platelet bleeds, we rarely transfuse platelets, since the benefit data is still lacking.

    • Abraham, The problem with factor VIIa for rapid neurosurg procedures is that while the coag tests will normalize; the patient may still be at increased bleeding risk. I think there is no advantage of VIIa over 4-factor PCCs for this use. Do you have evidence for the statement regarding the combination of PCC and VIIa. This combination is only for 3-factor PCCs and the VIIa you should add is to attempt to create something identical to 4-factor PCCs. The benefits are indisputable: 4-factor PCCs are more effective than 3 in the literature. The risks are tough to figure. The 4-factor you are creating is closer to FEIBA than beriplex or similar.

  4. Sean Riley says:

    Thank you for all of your work

  5. Chris Johnson says:

    Scott – I love the PCC’s.

    But what are the downsides? Are there big clotting complications? Is it expensive? In other words, should this completely replace FFP for anything – the hemodynamically stable GI Bleed that needs reversal, etc? Why would I use FFP at all anymore?

    • No downside except cost and the fact that PCC just gives factors and no volume. We wrestle with what the volume should be replaced with? Albumin? Hypertonic saline?

  6. Does Vitamin K really work in Liver patients?

    Interesting recent study: http://www.ncbi.nlm.nih.gov/pubmed/23080365

  7. Nick Childs says:

    Hi Scott,
    With regards antiplatelets and platelet infusions.
    Article from Medscape
    Reversal of Antiplatelet Therapy May Not Benefit TBI
    Laird Harrison
    October 29, 2013

    SAN FRANCISCO — Patients with traumatic brain injury may not benefit from transfusions of platelets to reverse their antiplatelet therapy, a new study shows.
    “Reversal of antiplatelet therapy was not associated with decreased progression of intracranial injury,” said Joshua Bauer, MS, a researcher at the University of Pittsburgh in Pennsylvania.
    Bauer presented the finding here at the Congress of Neurological Surgeons (CNS) 2013 Annual Meeting.
    Patients with hemorrhage who are receiving antiplatelet or anticoagulant medication for conditions such as atrial fibrillation pose a dilemma for physicians. The antiplatelet treatment protects them from ischemic stroke, but may — theoretically at least — worsen their hemorrhage.
    Many neurologic surgeons administer platelet transfusion in hope of slowing or stopping the hemorrhage, the authors note, but few studies have examined the effectiveness of this therapy.
    To fill that gap, Bauer and his colleagues carried out a retrospective comparative cohort study, looking at 797 patients older than age 65 years receiving antiplatelet therapy who were treated for traumatic brain injury at the University of Pittsburgh from 2006 to 2010.
    Of these, 270 had platelet transfusions and 517 did not. The patient groups were similar, although more of those not given transfusions were taking aspirin alone while those transfused were more likely to be taking clopidogrel or a combination of aspirin and clopidogrel.
    The researchers analyzed the patients’ scans to determine whether they had worsened.
    They found that the hemorrhage volume increased in 9% of the patients who had not been transfused vs 15% of those who had. The difference was nearly statistically significant (P = .05).
    In addition, the Rotterdam scores of hemorrhage severity worsened for 7% of the transfused patients vs 3% of the nontransfused patients, a finding that was significant (P = .01).
    However, when the researchers used a multivariate analysis to account for other predictors of hemorrhage progression, they found several: Glasgow Coma Scale score, Rotterdam score at admission, the volume of the hemorrhage, and the primary hemorrhage pattern.
    Controlling for these factors, they found no significant correlation between platelet transfusions and worsening hemorrhages.
    “It would inappropriate for me to say we were making patients worse by giving them a transfusion of platelets,” said Bauer.”What I can say is what the numbers show: that it doesn’t matter if you give someone platelets.”
    He speculated that platelet dose could make a difference. “The quantity of platelet transfusion could lead to quality of thrombosis,” he said.
    And it might be possible to identify patients who will benefit from antiplatelet therapy vs those who would not.
    “The data refutes the reflexive transfusion of patients on antiplatelet therapy in favor of a more judicious approach,” he said.
    In hope of providing guidelines to such an approach, the researchers have started a prospective trial in which they use a platelet dysfunction text to determine which patients should be transfused and which should not. They also hope to monitor cardiac events in these patients.
    In the question-and-answer period, an audience member asked whether the researchers had determined if patients fared better or worse if they were taking aspirin or clopidogrel, and Bauer responded that it did not appear to make a difference.
    Another questioner asked whether the researchers had measured the quantity of the platelet transfusions. Those data were not available, Bauer said.
    Asked to comment, Charles Agbi, MD, an associate professor of neurosurgery at the University of Ottawa in Ontario, Canada, told Medscape Medical News that he was not surprised by these results. “The hemorrhages tend to progress anyway,” said Dr. Agbi, who was not involved in the Bauer and colleagues’ study.
    In his own research, also presented here at CNS 2013, Dr. Agbi looked at how neurosurgeons are treating patients with subdural hemorrhages who are receiving anticoagulants because they have mechanical heart valves.
    “There’s always been a tug of war between the heart surgeons and the neurosurgeons as to how long they will let us stop the anticoagulants,” he said. “And for that reason there are no official guidelines. We don’t really know what’s safe.”
    Dr. Agbi and his colleagues sent out surveys to North American members of the American Association of Neurological Surgeons and the International Society of Thrombosis and Hemostasis and asked them how long they kept their patients off oral anticoagulants.
    They got 504 responses, spread almost evenly over the categories: 14.5% said 3 days or fewer, 22% said 4 to 5 days,19% said 6 to 7 days, 20% said 8 to 14 days, and the remainder said longer than 2 weeks.
    Dr. Agbi and his colleagues are planning a prospective trial in which they will measure patient outcomes to see whether they correlate with various intervals of anticoagulant cessation.
    “We want to find a way that we can establish the best thing for everyone to do,” he said.
    Mr. Bauer and Dr. Agbi have disclosed no relevant financial interests.
    Congress of Neurological Surgeons (CNS) 2013 Annual Meeting. Abstract #164 and #195. Presented October 22, 2013.

  8. Nick Childs says:

    Hi Scott,
    With regards antiplatelets and platelet infusions.
    Article from Medscape
    Reversal of Antiplatelet Therapy May Not Benefit TBI
    Laird Harrison
    October 29, 2013

    SAN FRANCISCO — Patients with traumatic brain injury may not benefit from transfusions of platelets to reverse their antiplatelet therapy, a new study shows.
    “Reversal of antiplatelet therapy was not associated with decreased progression of intracranial injury,” said Joshua Bauer, MS, a researcher at the University of Pittsburgh in Pennsylvania.
    Bauer presented the finding here at the Congress of Neurological Surgeons (CNS) 2013 Annual Meeting.
    Patients with hemorrhage who are receiving antiplatelet or anticoagulant medication for conditions such as atrial fibrillation pose a dilemma for physicians. The antiplatelet treatment protects them from ischemic stroke, but may — theoretically at least — worsen their hemorrhage.
    Many neurologic surgeons administer platelet transfusion in hope of slowing or stopping the hemorrhage, the authors note, but few studies have examined the effectiveness of this therapy.
    To fill that gap, Bauer and his colleagues carried out a retrospective comparative cohort study, looking at 797 patients older than age 65 years receiving antiplatelet therapy who were treated for traumatic brain injury at the University of Pittsburgh from 2006 to 2010.
    Of these, 270 had platelet transfusions and 517 did not. The patient groups were similar, although more of those not given transfusions were taking aspirin alone while those transfused were more likely to be taking clopidogrel or a combination of aspirin and clopidogrel.
    The researchers analyzed the patients’ scans to determine whether they had worsened.
    They found that the hemorrhage volume increased in 9% of the patients who had not been transfused vs 15% of those who had. The difference was nearly statistically significant (P = .05).
    In addition, the Rotterdam scores of hemorrhage severity worsened for 7% of the transfused patients vs 3% of the nontransfused patients, a finding that was significant (P = .01).
    However, when the researchers used a multivariate analysis to account for other predictors of hemorrhage progression, they found several: Glasgow Coma Scale score, Rotterdam score at admission, the volume of the hemorrhage, and the primary hemorrhage pattern.
    Controlling for these factors, they found no significant correlation between platelet transfusions and worsening hemorrhages.
    “It would inappropriate for me to say we were making patients worse by giving them a transfusion of platelets,” said Bauer.”What I can say is what the numbers show: that it doesn’t matter if you give someone platelets.”
    He speculated that platelet dose could make a difference. “The quantity of platelet transfusion could lead to quality of thrombosis,” he said.
    And it might be possible to identify patients who will benefit from antiplatelet therapy vs those who would not.
    “The data refutes the reflexive transfusion of patients on antiplatelet therapy in favor of a more judicious approach,” he said.
    In hope of providing guidelines to such an approach, the researchers have started a prospective trial in which they use a platelet dysfunction text to determine which patients should be transfused and which should not. They also hope to monitor cardiac events in these patients.
    In the question-and-answer period, an audience member asked whether the researchers had determined if patients fared better or worse if they were taking aspirin or clopidogrel, and Bauer responded that it did not appear to make a difference.
    Another questioner asked whether the researchers had measured the quantity of the platelet transfusions. Those data were not available, Bauer said.
    Asked to comment, Charles Agbi, MD, an associate professor of neurosurgery at the University of Ottawa in Ontario, Canada, told Medscape Medical News that he was not surprised by these results. “The hemorrhages tend to progress anyway,” said Dr. Agbi, who was not involved in the Bauer and colleagues’ study.
    In his own research, also presented here at CNS 2013, Dr. Agbi looked at how neurosurgeons are treating patients with subdural hemorrhages who are receiving anticoagulants because they have mechanical heart valves.
    “There’s always been a tug of war between the heart surgeons and the neurosurgeons as to how long they will let us stop the anticoagulants,” he said. “And for that reason there are no official guidelines. We don’t really know what’s safe.”
    Dr. Agbi and his colleagues sent out surveys to North American members of the American Association of Neurological Surgeons and the International Society of Thrombosis and Hemostasis and asked them how long they kept their patients off oral anticoagulants.
    They got 504 responses, spread almost evenly over the categories: 14.5% said 3 days or fewer, 22% said 4 to 5 days,19% said 6 to 7 days, 20% said 8 to 14 days, and the remainder said longer than 2 weeks.
    Dr. Agbi and his colleagues are planning a prospective trial in which they will measure patient outcomes to see whether they correlate with various intervals of anticoagulant cessation.
    “We want to find a way that we can establish the best thing for everyone to do,” he said.
    Mr. Bauer and Dr. Agbi have disclosed no relevant financial interests.
    Congress of Neurological Surgeons (CNS) 2013 Annual Meeting. Abstract #164 and #195. Presented October 22, 2013.

  9. Hey Scott,
    Interesting emrap session this month discusses chronic liver disease patients and that they may truly actually be hypercoaguable (due to concomitant loss of proclotting factors, etc), and that INR doesn’t necessarily correlate with bleeding/clotting risk. Curious to know your take on the topic..

    Sam

    • there is a post coming on the topic, but the answer is we don’t know. When they are bleeding, they have coagulopathy–there is no doubt. The question is do we need to reverse a non-bleeding patient for procedures, etc. I would like to see TEGs on these pts.

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