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Date: June 5th, 2017

Reference: Baharoglu et al. Platelet transfusion versus standard care after acute stroke due to spontaneous cerebral haemorrhage associated with antiplatelet therapy (PATCH): a randomised, open-label, phase 3 trial. Lancet 2016.

Guest Skeptic: Dr. Robert Edmonds is an Emergency Medicine staff physician in Newport News, VA and a recent graduate of the University of Missouri-Kansas City EM residency.

DISCLAIMER – The views and opinions of this podcast/blog do not reflect the views and opinions of the US Air Force, the United States Government, or Langley Air Force Base.

Case: Your next patient is a 68-year-old with sudden onset right sided hemiparesis and facial droop.  Non-contrast head CT shows a hemorrhagic stroke.  On review of the patient’s medications you notice the patient is taking daily aspirin. You wonder if they would benefit from a platelet transfusion.

Background: In the US, daily or every other day aspirin use has been reported to be as high as 61% in adults aged 65 or older (Ajani et al Am J Prev Med 2006).  Taking antiplatelet therapy prior to a hemorrhagic stroke raises the risk of death by 27% and in high income countries more than 25% of patients with incident intracerebral hemorrhages were taking antiplatelet therapy (Thompson et al Neurology 2010).  Many physicians are faced with patients with intracerebral hemorrhage on antiplatelets, and how to best manage them.

The reversal of antiplatelet medications in intracerebral hemorrhage was covered in a Best Available Evidence (Martin and Conlon Ann Emerg Med 2013). It stated that “none of these studies showed a mortality benefit or improved functional outcome with platelet transfusion in patients with spontaneous or traumatic intracerebral hemorrhage who were receiving antiplatelet medications.”

That review further elaborated that for these patients there were “no compelling data currently supporting the use of platelet transfusion” and that “it would be within the standard of care to withhold platelet transfusion in patients with either spontaneous or traumatic intracerebral hemorrhage who are receiving antiplatelet therapy.”  The review did note that the existing evidence at that time were all based on relatively small and retrospective.

However, recommendations from the neurosurgical perspective differ.  A 2010 World of Neurosurgery literature review on the topic by Campbell et al “at present, the literature contains insufficient information to establish any guidelines or treatment recommendations. In light of this, the current authors have proposed a protocol for antiplatelet reversal in both spontaneous and traumatic acute ICH.”

Clinical Question: Does platelet transfusion reduce death or dependency in acute hemorrhagic stroke for patients on antiplatelet agents?

Reference: Baharoglu et al. Platelet transfusion versus standard care after acute stroke due to spontaneous cerebral haemorrhage associated with antiplatelet therapy (PATCH): a randomised, open-label, phase 3 trial. Lancet 2016.

  • Population: Adults 18 years or older with non-traumatic intracerebral hemorrhage with a GCS of greater than seven in whom platelets could be transfused within six hours of symptom onset and used antiplatelet therapy for at least seven days.
    • Exclusions: Epidural or subdural hematoma, underlying aneurysm or arteriovenous malformation, planned surgery within 24hrs, intraventricular blood more than sedimentation in the posterior horns, previous adverse reaction to platelet transfusion, known use of vitamin K antagonists or history of coagulopathy, know thrombocytopenia, lacking mental capacity or death appeared imminent.
  • Intervention: Platelet transfusions within six hours of ICH of symptom onset and within 90 minutes of diagnostic brain imaging.
  • Comparison: Standard care
  • Outcome:
    • Primary Outcome: Shift towards death or dependence scored with the modified Rankin Scale (mRS) at three months
    • Secondary Outcomes: Survival, poor outcome (mRS 4-6), poor outcome (mRS 3-6), hemorrhage growth after 24hrs, transfusion issues (reactions and thrombotic complications) and other serious adverse events.

mRS

Authors’ Conclusions: “Platelet transfusion seems inferior to standard care for people taking antiplatelet therapy before intracerebral haemorrhage. Platelet transfusion cannot be recommended for this indication in clinical practice.”

Quality Checklist for Randomized Clinical Trials:

  1. checklistThe study population included or focused on those in the emergency department. Unsure. Not explicitly stated.
  2. The patients were adequately randomized. Yes
  3. The randomization process was concealed. Yes
  4. The patients were analyzed in the groups to which they were randomized. Yes. They performed an intention-to-treat protocol but also did an as-treated analysis.
  5. The study patients were recruited consecutively (i.e. no selection bias). Unsure. It was not mentioned in the paper or the study protocol that was published in 2010.
  6. The patients in both groups were similar with respect to prognostic factors. Yes. With the exception of a difference in peripheral arterial disease (16% in the treatment group and 4% in the standard group).
  7. All participants (patients, clinicians, outcome assessors) were unaware of group allocation. No. Patients and clinicians were aware of group allocation-the outcome assessors were not.
  8. All groups were treated equally except for the intervention. Yes
  9. Follow-up was complete (i.e. at least 80% for both groups). Yes. There was 100% follow-up.
  10. All patient-important outcomes were considered. Yes
  11. The treatment effect was large enough and precise enough to be clinically significant. Yes

Key Results: There were 190 patients randomized in this study (97 in the treatment group and 93 in the standard care group) with a mean age of 74 years.

Odds of death or dependence (mRS 4-6) was greater in the platelet transfusion group.

  • Primary Outcome:
    • Unadjusted OR of mRS 4-6 was 1.84 (95% CI; 1.10 to 3.08, p=0.02) in the treatment group
    • Adjusted OR of mRS 4-6 was 2.05 (95% CI; 1.18 to 3.56, p=0.0114) in the treatment group (note the adjustment was for pre-intracerebral hemorrhage antiplatelet therapy and known prognostic factors)
  • Secondary Outcomes:
    • PATCH Secondary outcomesTransfusion issues (reactions and thrombotic complications: One patient had a minor transfusion reaction while there was no difference in thrombotic complicaitons (four in treatment vs. one in standard)
    • Any Serious Adverse Events: 42% treatment vs. 29% standard OR 1.79 (95 CI; 0.98 to 3.27) in the intention-to treat analysis.

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1) Emergency Department Patients: We are not sure if these patients were emergency department patients because it was not explicitly stated in the paper. Given the nature of the complaint, it seems likely that they were.

2) Consecutive Recruitment: It was not documented whether patients were recruited consecutively. However, it does say in the paper that PATCH investigators did not need to keep a screening log. This means we are unable to know if there was any selection bias introduced into the study.

3) Lack of Blinding: Participants and local investigators were not masked to treatment allocation and this does have the potential to introduce some bias.  However, it was contrary to the study hypothesis that platelet transfusion would have positive patient oriented effect. This makes the results more believable.

4) Effect Size and Precision: The adjusted OR for the primary outcome was 2.05 but the lower end of the 95% confidence interval was close to one. In addition, the confidence interval was fairly wide.

5) More Data: They say in the discussion that a similar RCT is nearing completion (NCT00699621). When that study is searched for on ClinicalTrials.gov no results are posted and the page says: “The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years”.

Comment on Authors’ Conclusion Compared to SGEM Conclusion: We generally support the authors’ conclusion and do not recommend platelet transfusion for reversal of antiplatelet drugs in spontaneous intracereberal hemorrhage.

SGEM Bottom Line: There appears to be evidence of harm if platelet transfusion is given to reverse antiplatelet agents in patients with atraumatic intracerebral hemorrhage, so this practice cannot be recommended.

Case Resolution: You discuss care with the patient and manage their case without the use of a platelet transfusion.  The patient is transferred to the neuro ICU and a month later, ambulates to your emergency department to thank you for their care.

Dr. Robert Edmonds

Dr. Robert Edmonds

Clinically Application: Hemorrhagic stroke patients on antiplatelet drugs appear to have a risk of harm from platelet transfusion, so it should not be part of their care unless future studies show benefit.

What Do I Tell My Patient? Although you are on medications that inhibit the function of your body’s platelets, a cell that assists with clotting, giving fresh platelets would not be helpful, and based on recent evidence, might actually be harmful.

Keener Contest: Last weeks’ winner was Shyam Murali a medical student from Texas A&M. They knew that an abdominal and pelvic CT is equivalent to about three years of background radiation (RadiologyInfo).

Listen to the episode on iTunes to here the question for this week.  If you know the answer then send an email to TheSGEM@gmail.com with “keener” in the subject line. The first correct answer will receive a cool skeptical prize.

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Remember to be skeptical of anything you learn, even if you heard it on the Skeptics’ Guide to Emergency Medicine.

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