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Continuing from Part I.

A part of this study that should received more attention is the rate of immediate tICH (traumatic IntraCranial Hemorrhage) among patients taking clopidogrel or warfarin.

5.1% of warfarin (Coumadin) patients had immediate traumatic intracranial hemorrhage.

12.0% of clopidogrel (Plavix) patients had immediate traumatic intracranial hemorrhage.

The sample was from all patients with any kind of head trauma who presented to the participating trauma centers or to the participating community hospitals. From major head trauma transported to a trauma center through to minor head trauma, such as the patient transported to a community hospital because of a nursing home slid out of bed in the dementia unit and might have hit head protocol. This should increase the relevance of this study to emergency physicians in community hospitals and could affect the decisions about where to transport these patients.

More than 60% of patients with immediate traumatic intracranial hemorrhage in both warfarin and clopidogrel cohorts had a normal mental status (GCS score = 15).^[1]

Does that mean that tICH is more common with a normal GCS (Glasgow Coma Scale/Score) than with a lower GCS?

No.

Definitely not.

From Table 4, there are 45 tICH patients with a GCS of 15. There are a total of 70 tICH patients. 45/70 = 64.3%.

Only 64.3% of patients with a tICH had a GCS of 15, while the patients with a GCS of 15 made up 87.6% of the patients evaluated for head injury. 3.6% of the warfarin patients with a GCS of 15 had immediate tICH, while 9.2% of the clopidogrel patients with a GCS of 15 had immediate tICH.

Only 12.4% of the patients had a GCS <15, but they made up 35.7% of the cases of tICH.

Suppose we don't require a GCS of 15, but only ≥13. Those with a GCS of 12 or less made up 2.7% of patients, but 15.7% of the cases of tICH. It appears that the lower the GCS, the greater the likelihood of tICH, but a GCS of 15 is not a reason to assume that there is no head injury, especially if the patient is taking clopidogrel.

1/11 clopidogrel patients (GCS of 15 and hit head) will have a bleed vs. 1/28 warfarin (GCS of 15 and hit head) patients. Are the newer drugs better? Will the claimed better than clopidogrel drugs be better at avoiding side effects or will they be better at causing intracranial bleeding from minor injuries? The newer drugs include prasugrel (Effient), ticagrelor (Brilinta), dabigatran (Pradaxa), rivaroxaban (Xarelto), and others.

We don’t know yet, but it would not be reasonable to assume that these drugs will be safer.

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Should all anticoagulated patients receive a CT scan, regardless of how unremarkable their physical exam?

According to the authors, yes. However, they did not scan every patient. There were 64 patients who did not receive CT scans. This is about 2/3 of the size of the study that claims that these patients should be observed in the hospital for 24 hours, then receive another CT scan.^[2]

How reckless was skipping the CT on these apparently uninjured patients?

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Click on image to make it larger.

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Zero patients with tICH.

This is from a very small number (64 patients), so it is not good evidence (and the authors do not claim that this is good evidence), but this is almost on a par with numbers in the Menditto study (97 patients).^[2] With small numbers, we can come up with answers that satisfy almost any hypothesis.

Is there good evidence for admission and a 24 hour observation period followed by a second CT scan for every anticoagulated patient with any head trauma?

No.

Is there good evidence for a CT scan for every anticoagulated patient with any head trauma?

Yes. Until there is a good way to decide which patients do not need to be scanned. The problem is that there does not appear to be a good substitute for a CT scan – and even the CT scan misses tICH (delayed tICH).

27/70 (38.7%) tICH patients had neurosurgery or died.

How many of them had a GCS of 15?

How many of them had a GCS of ≥13?

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What was it about these patients that encouraged the doctors to not use a CT scan on the 64 patients who did not receive a CT scan?

We do not know.

When we look at the delayed tICH patients, we will see that there is not an easy way to pick out the slow bleeds from the GCS, INR, mechanism, or anything else.

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Table 4 shows that those 45 tICH patients are out of 45/870 patients with a GCS of 15. 45/870 is 5.2%. This is from Table 4, out of the total of 1,064 patients, so why do they state elsewhere that there are 932 patients (87.6%) with a GCS of 15? Where are the 62 patients who make up the difference? The footnote states that this is ^*Based on patients who received a cranial CT scan on initial evaluation after head injury. The conclusion appears to be that 62/64 (96.9%) patients, who did not have a CT scan, did have an initial GCS of 15. That makes sense. 45/870 patients who had a GCS of 15, had a CT scan, and had an immediate tICH.

Normal mental status (GCS = 15) – 932 (87.6%).

752 (70.7%) patients had physical examination findings of head trauma above the clavicles, but only 707 of those patients had CT scans and 50/707 (7.1%) had immediate tICH. 45 patients with physical examination findings of head trauma above the clavicles do not appear to have had a CT scan. 45 (70.3%) of the 64 patients who did not have a CT scan, do appear to have had physical examination findings of head trauma above the clavicles. When reading the results in Table 4, this appears to be the explanation for the differences in the numbers. It would be nice if this were clearer on the first reading of the paper.

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To be continued in Part III and Part IV.

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Footnotes:

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^[1] Immediate and delayed traumatic intracranial hemorrhage in patients with head trauma and preinjury warfarin or clopidogrel use.
Nishijima DK, Offerman SR, Ballard DW, Vinson DR, Chettipally UK, Rauchwerger AS, Reed ME, Holmes JF; Clinical Research in Emergency Services and Treatment (CREST) Network.
Ann Emerg Med. 2012 Jun;59(6):460-468.e7.
PMID: 22626015 [PubMed – in process]

There is a podcast covering this at Annals of Emergency Medicine. Podcast on this article in Mp3 format.

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^[2] Management of Minor Head Injury in Patients Receiving Oral Anticoagulant Therapy: A Prospective Study of a 24-Hour Observation Protocol.
Menditto VG, Lucci M, Polonara S, Pomponio G, Gabrielli A.
Ann Emerg Med. 2012 Jan 13. [Epub ahead of print]
PMID: 22244878 [PubMed – as supplied by publisher]

Free Full Text from Annals of Emergency Medicine

There is a separate podcast covering this article at Annals of Emergency Medicine. Podcast on this article in Mp3 format.

I covered this in January in This is the Way to Bad Medicine.

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Menditto, V., Lucci, M., Polonara, S., Pomponio, G., & Gabrielli, A. (2012). Management of Minor Head Injury in Patients Receiving Oral Anticoagulant Therapy: A Prospective Study of a 24-Hour Observation Protocol Annals of Emergency Medicine DOI: 10.1016/j.annemergmed.2011.12.003

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Nishijima, D., Offerman, S., Ballard, D., Vinson, D., Chettipally, U., Rauchwerger, A., Reed, M., & Holmes, J. (2012). Immediate and Delayed Traumatic Intracranial Hemorrhage in Patients With Head Trauma and Preinjury Warfarin or Clopidogrel Use Annals of Emergency Medicine, 59 (6), 460-2147483647 DOI: 10.1016/j.annemergmed.2012.04.007

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This is the final paper on head trauma and anticoagulants from the current Annals of Emergency Medicine. I wrote about the pair of editorials and the other article earlier.^[1],^[2] There is a lot to write about in this paper, so I am glad that this is a very well done paper. It is a pleasure to read research on an important topic and not be disappointed.

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What question this study addressed
What is the incidence and prevalence of immediate and delayed traumatic intracranial hemorrhage in patients with blunt head trauma who are receiving clopidogrel and warfarin?^[3]

Some anticoagulated patients who hit their heads will initially not appear injured, will even have CT (Computerized Tomography) scans that show no injury, but will later develop significant intracranial bleeding.

How many are Some?

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The potential risk for both immediate and delayed traumatic intracranial hemorrhage has generated guidelines recommending routine cranial CT imaging and hospital admission for neurologic observation in head-injured patients receiving warfarin.^{11-14 [3]}

Unfortunately, this is the first good study of these patients, so these guidelines have not been based on good evidence.

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We hypothesized that the prevalence for immediate traumatic intracranial hemorrhage was similar between patients receiving clopidogrel and those receiving warfarin and that the cumulative incidence of delayed traumatic intracranial hemorrhage in both groups was less than 1%.^[3]

The lack of good evidence for traumatic ICH (IntraCranial Hemorrhage) with clopidogrel (Plavix) compared with warfarin (Coumadin) highlight the problem of being overly optimistic with new drugs.

We act as if the newer drugs magically solve the problems of the older drugs. The newer drugs may not provide more safety. The only thing we can be sure of is that the newer drugs do provide more uncertainty.^[4] Without good research, we are only praying for better outcomes.

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Setting and Selection of Participants
Adult (aged ≥18 years) emergency department (ED) patients with blunt head trauma and preinjury warfarin or clopidogrel use (within the previous 7 days) were enrolled. We defined blunt head trauma as any blunt head injury regardless of loss of consciousness or amnesia. We excluded patients with known injuries who were transferred from outside facilities because their inclusion would falsely inflate the prevalence of traumatic intracranial hemorrhage. Additionally, patients with concomitant warfarin and clopidogrel use were excluded.^[3]

These are reasonable exclusions. This limits the patients to adult patients transported from the scene having taken clopidogrel or warfarin in the past week, but not taking both. We shouldn’t try to answer every question at once.

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Click on images to make them larger.

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Delayed traumatic intracranial hemorrhage was defined as traumatic intracranial hemorrhage on cranial CT scan, occurring within 14 days after an initial normal CT scan result and in the absence of repeated head trauma.^[3]

Any intracranial bleeding after the initial assessment.

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Patients were admitted to the hospital at the discretion of the emergency physician. Patients with normal cranial CT scan results and therapeutic international normalized ratio levels are not reversed at the participating centers.^[3]

The authors do appear to be more conservative, intervention-wise, than many trauma centers, but they also appear to be demonstrating a very good understanding of what is important in research.

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While they did not scan everyone, they did come close to everyone – 94% of all patients. This is not the study to cite to avoid scanning head injuries.

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Our study is unique in that a majority of patients were evaluated at community hospitals. Furthermore, we included all patients with any degree of head trauma.^[3]

They are looking at the patients in the setting that matters – not just in the trauma center with all of the specialists in house.

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The cumulative incidence of delayed traumatic intracranial hemorrhage was assessed in the 930 patients with an initial normal cranial CT scan by telephone survey (843; 90.6%) or electronic medical record review (83; 8.9%). Of the 4 patients lost to follow-up, none was identified in the Social Security Death Index.^[3]

This is quite a bit different from the massaged small numbers used to produce a 6% delayed ICH rate that would justify keeping the patient in the hospital for 24 hours.

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Image credit.

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How many days are in a 24 hour observation period?

Three of the four patients with delayed ICH were admitted to the hospital from the ED (Emergency Department), but two of them did not have the ICH detected until several days later. The one delayed ICH patient discharged home did not appear to have symptoms until three days later.

The protocol to keep everyone for 24 hours, then re-scan everyone, would probably have missed three of these four patients. We cannot be sure, but three appear to have been asymptomatic for a couple of days beyond the 24 hour observation period recommended by some. The only patient with a delayed ICH detected within a day was discharged home at four days without treatment and without any known complications.

What about the immediate ICH patients? That will be in Part II and there will be further discussion of the delayed ICH patients in Part III and Part IV.

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Footnotes:

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^[1] Validation of the Dime
Rogue Medic
Thu, 24 May 2012
Article

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^[2] This is the Way to Bad Medicine
Rogue Medic
Tue, 24 Jan 2012
Article

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^[3]Immediate and delayed traumatic intracranial hemorrhage in patients with head trauma and preinjury warfarin or clopidogrel use.
Nishijima DK, Offerman SR, Ballard DW, Vinson DR, Chettipally UK, Rauchwerger AS, Reed ME, Holmes JF; Clinical Research in Emergency Services and Treatment (CREST) Network.
Ann Emerg Med. 2012 Jun;59(6):460-468.e7.
PMID: 22626015 [PubMed – in process]

There is supposed to be a podcast covering this at Annals of Emergency Medicine, but the podcast for June has not yet been posted. Page for all Annals of Emergency Medicine podcast.

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^[4] Newer and Better Medications
Rogue Medic
Thu, 31 May 2012
Article

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Nishijima, D., Offerman, S., Ballard, D., Vinson, D., Chettipally, U., Rauchwerger, A., Reed, M., & Holmes, J. (2012). Immediate and Delayed Traumatic Intracranial Hemorrhage in Patients With Head Trauma and Preinjury Warfarin or Clopidogrel Use Annals of Emergency Medicine, 59 (6), 460-2147483647 DOI: 10.1016/j.annemergmed.2012.04.007

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