EBQ:Platelet transfusion versus standard care after acute stroke due to spontaneous cerebral haemorrhage associated with antiplatelet therapy (PATCH): a randomized, open-label, phase 3 trial

incomplete Journal Club Article

. "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. :2605-13.
PubMed Full text

Clinical Question

In patients on antiplatelet therapy with acute spontaneous primary intracranial hemorrhage, does a platelet transfusion with standard care result in reduced death or spread of the intracerebral hemorrhage compared to standard care alone?

Conclusion

• In patients who are on antiplatelet therapy who suffer from a primary intracranial hemorrhage (ICH), had increased serious adverse events during hospital stay.
• Platelets are not routinely recommended for patients on antiplatelet therapy who have an ICH.

Major Points

• Hemorrhagic stroke is responsible for half of all stroke deaths with atraumatic ICH accounting for 2.3 of hemorrhagic strokes
• Given than over a quarter of all patients with ICH are on antiplatelet therapy and that platelet transfusions have been used in these patients 18, this study sought to do a randomized controlled trial to see if data supports its use

Study Design

• Multicenter, randomized, open-label, parallel-group trial in 36 hospitals in the Netherlands, 13 hospitals in UK and 11 hospitals in France
• Randomized with number generator
• Stratified by
  • type of ICH
  • antiplatelet therapy whether ASA, clopidogrel, ASA+ dipyramidole, ASA +clopidogrel)
• NIHSS calculated for all patients
• Brain imaging done
• Standard care- leucocyte-depleted platelet transfusions
• Platelet transfusion initiated within 6 hours of ICH symptom onset and within 90 minutes
  • One platelet for patients on ASA or ASA+dipyramidole
  • Two platelets for patients on ASA+clopidogrel
• Measured Rankin score 3 months from initial platelet transfusion
• Imaging at 24 hours after randomization
• Stratified the analysis
  • ICH volume size
  • hospitals where treatments took place
• Adverse events
  • Transfusion reactions, thrombotic complications
  • Hemorrhage enlargement
  • Intraventricular extension
  • Hydrocephalus
  • Edema
  • Brain herniation
  • Epileptic seizures
  • Infection

Population

Patients greater than 18 on an anti-platelet agent with atraumatic ICH presenting to 60 hospitals in Netherlands, UK and France

Inclusion Criteria

• Must meet all the criteria
  • 18 years or older with nontraumatic supratentorial intracerebral hemorrhage confirmed by brain imaging
  • GCS>8
  • Platelet transfusion could be initiated within
    • 6 hours of symptom onset and
    • 90 min of brain imaging
  • On antiplatelet therapy for at least 7 days prior either
    • Aspirin, Carbasalate calcium, clopidogrel, dipyridamole
  • Pre-intracerbral hemorrhage modified Rankin Scale of 0 or 1

Exclusion Criteria

• Treating physician thinks imaging suggestive of epidural or subdural hematoma
• Underlying anseurysm, AVM
• Planned surgical evacuation of ICH within 24 hours of admission
• IV blood more than sedimentation in the posterior horns of the lateral ventricles
• Previous adverse reaction to platelet transfusion
• Known use of vitamin K antagonist
• History of coagulopathy
• Known thrombocytopenia
• Lacking mental capacity by national legal standards prior to ICH
• Death appeared imminent
• Infratentorial or large IVH 2/2 likely to undergo surgical Interventions

Interventions

• 1 or 2 unit platelet transfusion

Outcomes

Primary Outcome

Death at three months or growth of ICH at three months

Secondary Outcomes

• Any adverse events
  • 42% in platelet transfusion had adverse event
  • 29% in standard therapy had adverse event
• ICH enlargement, brain edema, brain herniation, intraventricular extension, hydrocephalus
• Urinary or pulmonary infections
• Thromboembolism – ischemic stroke, myocardial infarction, extremity embolism, pulmonary embolism
• Transfusion reactions- nonhemolytic, anaphylactic, acute lung injury, post-transfusion purpura, graft versus host disease, transmitted bacterial infection

seizures

Criticisms & Further Discussion

• Randomized trial of 189 participants who were taking antiplatelet therapy with atraumatic ICH
• platelet transfusion did not improve patient outcomes

• European countries (high income countries- can this be generalized to lower income countries)
• Small sample size
• most patients were on Aspirin unclear if this can be generalized to patients on only Plavix
• unknown if patients were actually compliant with medications, did it based on self report
• 19% of participants met at least one of the exclusion outcomes