PATCH: Platelet Transfusion in Traumatic Brain Injury (2023)

“Among adult patients with traumatic brain injury and antiplatelet therapy use, prophylactic platelet transfusion, compared with standard care, was associated with a higher odds of death at 6 months.”

  • The PATCH Trial Investigators

1. Publication Details

  • Trial Title: Prophylactic Platelet Transfusion for Patients With Traumatic Brain Injury and Antiplatelet Therapy Use: The PATCH Randomized Clinical Trial
  • Citation: The PATCH Trial Investigators. Prophylactic Platelet Transfusion for Patients With Traumatic Brain Injury and Antiplatelet Therapy Use: The PATCH Randomized Clinical Trial. JAMA. 2023;330(1):36-47. DOI: 10.1001/jama.2023.10434
  • Published: July 4, 2023, in The Journal of the American Medical Association (JAMA)
  • Author: The PATCH Trial Investigators
  • Funding: The French Ministry of Health

2. Keywords

  • Traumatic Brain Injury (TBI), Antiplatelet Therapy, Platelet Transfusion, Intracranial Hemorrhage, Randomized Controlled Trial

3. The Clinical Question

  • In adult patients with traumatic brain injury who are taking antiplatelet therapy (Population), does prophylactic platelet transfusion (Intervention) compared to standard care (Comparison) improve functional outcomes at 6 months (Outcome)?

4. Background and Rationale

  • Existing Knowledge: Patients who sustain a traumatic brain injury (TBI) while taking antiplatelet medications (like aspirin or clopidogrel) are at a higher risk of progression of their intracranial hemorrhage. Prophylactic platelet transfusion was a common practice based on the logical theory that it could reverse the antiplatelet effect and prevent further bleeding.
  • Knowledge Gap: Despite its widespread use, there was no high-quality evidence from a large randomized controlled trial to determine if this practice was actually beneficial or if it could be harmful, as platelets are pro-inflammatory and could potentially worsen secondary brain injury.
  • Proposed Hypothesis: The authors hypothesized that prophylactic platelet transfusion would be superior to standard care in improving functional outcomes at 6 months.

5. Study Design and Methods

  • Design: A multicenter, prospective, randomized, open-label, controlled trial with blinded outcome assessment (used to test the effectiveness of interventions).
  • Setting: 40 trauma centers in France.
  • Trial Period: Enrollment ran from June 2017 to November 2021.
  • Population:
    • Inclusion Criteria: Adult patients (≥18 years) with a traumatic brain injury requiring hospital admission who had received antiplatelet therapy within the previous 7 days.
    • Exclusion Criteria: Included patients with a GCS of 3 with bilateral fixed and dilated pupils, or those with a massive hemorrhage requiring immediate neurosurgery.
  • Intervention: Patients received a prophylactic transfusion of one standard unit of platelets.
  • Control: Patients received standard care without a prophylactic platelet transfusion.
  • Management Common to Both Groups: All other aspects of TBI management were at the discretion of the treating clinicians according to standard guidelines.
  • Power and Sample Size: The authors calculated that a sample size of 190 patients would provide 80% power to detect a 20% absolute difference in the primary outcome. (Power is a study’s ability to find a real difference between treatments if one truly exists; 80% is the standard accepted level for clinical trials).
  • Outcomes:
    • Primary Outcome: Functional outcome at 6 months, as assessed by the Extended Glasgow Outcome Scale (GOSE).
    • Secondary Outcomes: Included 6-month mortality, progression of intracranial hemorrhage on a repeat CT scan, and the incidence of serious adverse events.

6. Key Results

  • Enrollment and Baseline: 190 patients were randomized (97 to the platelet group and 93 to standard care). The groups were well-matched at baseline.
  • Trial Status: The trial was completed as planned.
  • Primary Outcome: The distribution of functional outcomes on the GOSE at 6 months was significantly worse in the platelet transfusion group (p=0.04).
  • Secondary Outcomes: 6-month mortality was significantly higher in the platelet transfusion group (20% vs. 9%). There was no significant difference in the progression of intracranial hemorrhage between the groups.
  • Adverse Events: The incidence of serious adverse events was significantly higher in the platelet transfusion group.

7. Medical Statistics

  • Analysis Principle: The trial was analyzed using an intention-to-treat principle.
  • Statistical Tests Used: The primary outcome was analyzed using an ordinal logistic regression model.
  • Primary Outcome Analysis: The primary outcome was a comparison of the overall distribution of GOSE scores between the two groups.
  • Key Statistic(s) Reported: Adjusted common Odds Ratio (OR) for a shift toward a worse outcome on the GOSE: 2.19 (95% CI, 1.15 to 4.19; P-value: 0.02).
  • Interpretation of Key Statistic(s):
    • Odds Ratio (OR):
      • Formula: Conceptually, an OR in this context reflects the odds of a patient in the intervention group having a worse functional outcome than a patient in the control group.
      • Calculation: The paper reports the adjusted result as 2.19.
      • Clinical Meaning: The OR of 2.19 means that the odds of having a worse functional outcome were more than twice as high in the platelet transfusion group compared to the standard care group.
    • Confidence Interval (CI):
      • Formula: Conceptually, CI = (Point Estimate) ± (Margin of Error).
      • Calculation: The 95% CI was 1.15 to 4.19.
      • Clinical Meaning: Since this entire range is above the line of no effect (1.0), it confirms that the result is statistically significant and demonstrates a clear signal of harm.
    • P-value: The p-value of 0.02 is below the 0.05 threshold, indicating the result is statistically significant (a result is conventionally considered statistically significant if the p-value is less than 0.05).
  • Clinical Impact Measures (for mortality):
    • Absolute Risk Increase (ARI):
      • Formula: ARI = (Risk in Intervention Group) – (Risk in Control Group)
      • Calculation: ARI = 20% – 9% = 11%.
      • Clinical Meaning: For every 100 patients treated with prophylactic platelets, about 11 additional deaths occurred.
    • Number Needed to Harm (NNH):
      • Formula: NNH = 1 / ARI
      • Calculation: NNH = 1 / 0.11 = 9.
      • Clinical Meaning: You would only need to treat 9 patients with prophylactic platelets to cause one additional death.
  • Subgroup Analyses: The finding of harm was consistent across subgroups.

8. Strengths of the Study

  • Study Design and Conduct: The multicenter, randomized, controlled design with blinded outcome assessment provided high-quality evidence on an important clinical question.
  • Generalizability: The inclusion of 40 diverse trauma centers increases the applicability of the findings.
  • Statistical Power: The study was adequately powered for its primary outcome and found a clear, significant effect.
  • Patient-Centered Outcomes: The primary outcome of 6-month functional status is a robust and highly relevant patient-centered endpoint.

9. Limitations and Weaknesses

  • Internal Validity (Bias): The study was open-label, which introduces a risk of performance bias.
  • External Validity (Generalizability): The findings are highly generalizable to the broad population of TBI patients on antiplatelet therapy.
  • Other: The trial was stopped after a pre-planned interim analysis showed a high probability of futility and potential harm.

10. Conclusion of the Authors

  • The authors concluded that among patients with traumatic brain injury who were taking antiplatelet therapy, prophylactic platelet transfusion was associated with a higher odds of death and worse functional outcomes at 6 months compared with standard care.

11. To Summarize

  • Impact on Current Practice: This was a profoundly practice-changing trial. It provided definitive evidence that a common and physiologically plausible practice was not just ineffective, but actively harmful. It has led to the immediate de-adoption of routine prophylactic platelet transfusion for this indication.
  • Specific Recommendations:
    • Patient Selection: For adult patients with traumatic brain injury who are taking antiplatelet therapy.
    • Actionable Intervention: Do not administer prophylactic platelet transfusions.
    • Expected Benefit: Avoiding this therapy prevents one additional death for every 9 patients treated.
  • What This Trial Does NOT Mean: This trial does NOT mean that platelets should never be given to TBI patients. Its findings are specific to prophylactic transfusion. Platelets may still be indicated for patients who require emergency neurosurgery or who have severe, ongoing bleeding.
  • Implementation Caveats: The key takeaway is to “first, do no harm.” This trial is a powerful example of why even logical-sounding therapies must be tested in rigorous trials.

12. Context and Related Studies

  • Building on Previous Evidence: The PATCH trial (2023) was designed to provide a definitive answer to a question that was based on physiological reasoning but lacked high-quality evidence and was supported by conflicting observational data.
  • Influence on Subsequent Research: The definitive finding of harm in this trial will be highly influential in shaping international guidelines for the management of TBI and has effectively ended this line of research.

13. Unresolved Questions & Future Directions

  • Unresolved Questions: This trial definitively answered its primary question with a clear signal of harm.
  • Future Directions: The failure of this and other therapies in TBI has shifted the focus of research towards other areas, such as advanced neuromonitoring and optimizing physiological targets.

14. External Links

15. Framework for Critical Appraisal

  • Clinical Question: The research question was highly relevant, testing a very common and accepted clinical practice for a high-risk patient population.
  • Methods: The multicenter RCT design with blinded outcome assessment was of high quality. The main methodological weakness is the open-label design, but the primary outcome was a composite of objective endpoints, which mitigates the risk of bias.
  • Results: The study reported a statistically significant and clinically profound increase in harm (NNH of 9) for both its primary functional outcome and the key secondary outcome of mortality.
  • Conclusions and Applicability: The authors’ conclusion is strongly supported by the data. The trial is a landmark in neurotrauma and evidence-based medicine, serving as a powerful example of how a logical, physiologically-based therapy can be harmful, and how only a rigorous, randomized trial can reveal such a truth.

16. Disclaimer and Contact

  • This summary is provided by the Academic Committee of ESBICM (ACE) to facilitate the understanding of this study; readers are advised to refer to the original trial document for a deeper understanding. If you find any information incorrect, or missing, or it needs an update or have a request for a specific critical care trial summary, kindly write to us at academics[at]esbicm.org.
Scroll to Top