Without evidence of benefit, an intervention should not be presumed to be beneficial or safe.

- Rogue Medic

What is the effect of clopidogrel on head injuries? Part I


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.

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?

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?

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.

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.

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.

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.

Click on images to make them larger.

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.

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.

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.

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.

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.

Image credit.

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.


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

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

[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.

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

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



  1. […] What is the effect of clopidogrel on head injuries? Part I | Rogue Medic says: Wed, 13 Jun 2012 19:39:56 +0000 at Wed, 13 Jun 2012 19:39:56 +0000 […]

  2. […] from Part I, Part II, and Part III about the comparative effects of warfarin (Coumadin) and clopidogrel […]

  3. […] from Part I and Part II about the comparative effects of warfarin (Coumadin) and clopidogrel (Plavix) on tICH […]