You Can't PATCH Up An ICH

Clinical Scenario: A 65-year-old male with a history of coronary artery disease, hypertension, and diabetes presents to the ED complaining of a severe headache, nausea, and vomiting. He is protecting his airway and has no focal neuro deficits. A head CT shows a large left-sided intraparenchymal hemorrhage. As you’re about to page Neurosurgery, you scroll through his medication list and notice that he takes aspirin and clopidogrel daily. You know that the neurosurgeons frequently ask for platelet transfusions in these patients- should you just go ahead and order a couple of packs now?

Clinical Question: Does platelet transfusion improve short- or long-term outcomes for patients with spontaneous intracerebral hemorrhage (ICH) who are taking antiplatelet agents?

Literature Review: The first high-quality RCT on this topic, the PATCH trial, was recently published in the Lancet. Baharoglu and colleagues performed a multi-national, multi-center, randomized, open-label, masked-endpoint trial to assess the efficacy of platelet transfusion for patients taking antiplatelet agents who develop a non-traumatic ICH. Patients were eligible for enrollment if they met the following criteria:

  • 18+ years old
  • Non-traumatic ICH and a GCS of 8-15
  • Able to receive platelets within 6 hours of last known normal and within 90 minutes of brain imaging
  • Known to have been taking aspirin, carbasalate (an aspirin derivative that is frequently used in the UK), clopidogrel, or dipyridamole for at least 7 days
  • Pre-event modified Rankin score of 0 or 1.

Patients were excluded if they met any of the following criteria:

  • Presence of comorbid neurosurgical conditions (epidural hematoma, subdural hematoma
  • CT findings suspicious for underlying AVM or aneurysm
  • Significant intraventricular hemorrhage,
  • Expected surgical intervention for clot evacuation within 24 hours
  • Previous history of severe reaction to platelet transfusion
  • Use of vitamin K antagonists (unless INR <1.3 on presentation)
  • Known coagulopathy or thrombocytopenia with platelet count <100k,
  • Inability to provide consent prior to ICH due to mental disability, or imminent death.

Patients were randomized in a 1:1 ratio to receive “standard care” (not strictly defined, but presumed by the authors to correspond to current European neurosurgical guidelines) or “standard care” plus platelet transfusion. Randomization was blinded by means of a secure computerized system. Patients and treating physicians were aware of allocations, but outcome assessors and study investigators not involved in direct patient care were blinded. The primary outcome was shift towards death or dependence rated on the modified Rankin scale (mRS) at 3 months.

Overall, 190 patients were enrolled and randomized, 97 to transfusion and 93 to standard care. Baseline characteristics including severity of hemorrhage, GCS score on presentation, and comorbidities (other than PVD, more common in the platelet group) were similar between the groups. In the intention-to-treat analysis, the odds of a shift towards death or dependence on the mRS were actually higher in the transfusion group (adjusted common OR 2.05, 95% CI 1.18-3.56, p = 0.014). Secondary analysis showed that patients in the transfusion group were more likely to have a mRS of 4-6 (moderately severe disability, severe disability, or death) at 3 months (OR 2.04, 95% CI 1.12-3.74, p=0.0195). 42% (n=40)of participants receiving platelets had a “serious adverse event” during their index hospitalization, as compared to 29% (n=28) of participants receiving standard care.  The most serious adverse events were ICH enlargement or urinary or pulmonary infections.

The study did have some weaknesses. It was relatively small compared to other stroke trials, leading some chance imbalances between the groups; however, standard size calculations were performed and enrollment targets were achieved. It had very rigorous exclusion criteria (19% met at least one exclusion criteria), which render the trial inapplicable to a large number of patients presenting with ICH (especially the requirement that no surgery be planned within 24 hours). Study investigators did not keep screening logs, so it is not possible to evaluate the trial for inclusion bias. Finally, the investigators relied on patient/relative report and/or chart review rather than objective lab platelet function testing (which is expensive and not widely available) to identify patients taking antiplatelet agents, raising the possibility that some patients included were not actually taking these medications

Overall, however, the PATCH trial strongly suggests that the routine practice of treating patients with non-traumatic ICH who are taking antiplatelet agents with platelet transfusion is not helpful, and possibly harmful. It may be time to start discussing the risks and benefits of this treatment more thoroughly with our patients and consultants.

References:

  1. 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; 387: 2605–13

Kevin Baumgartner PGY2

Faculty Reviewed by Peter Panagos, MD, FACEP, FAHA

Washington University Emergency Medicine1 Comment