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PlAtelet Transfusion versus standard care after acute stroke due to spontaneous Cerebral Haemorrhage associated with antiplatelet therapy

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Year of Publication: 2016

Authors: Baharoglu MI, Cordonnier C, Al-Shahi Salman R, ..., Roos YB; on behalf of The PATCH Investigators

Journal: The Lancet

Citation: Lancet 2016;387(10038):2605-2613

Link: https://doi.org/10.1016/S0140-6736(16)30392-0

Clinical Question

Does platelet transfusion reduce death or dependence compared to standard care in patients with acute spontaneous intracerebral hemorrhage who were taking antiplatelet therapy?

Bottom Line

Platelet transfusion is HARMFUL in acute ICH patients on antiplatelet therapy. It increased the odds of death or dependence by 2-fold compared to standard care and cannot be recommended for this indication.

        Major Points
        First randomized trial of platelet transfusion for acute ICH in patients on antiplatelet therapy
Platelet transfusion significantly worsened functional outcomes (adjusted OR 2.05, p=0.01)
72% of platelet transfusion group had mRS 4-6 vs 56% in standard care group
No significant reduction in hematoma growth with platelet transfusion
Findings consistent across subgroups (single vs dual antiplatelet, country, ICH volume)
Possible mechanisms of harm: pro-thrombotic effects, inflammation, impaired collateral perfusion
Trial stopped at pre-specified sample size, not for futility or harm

      

Design

Study Type: Randomized, open-label, masked endpoint (PROBE), phase 3 trial

Randomization: 1

Blinding: Open-label for participants and treating clinicians; outcome assessors and data analysts masked to treatment allocation

Enrollment Period: February 2009 to October 2015

Follow-up Duration: 3 months

Centers: 60

Countries: Netherlands, United Kingdom, France

Sample Size: 190

Analysis: Intention-to-treat; ordinal logistic regression of mRS shift adjusted for stratification variables (antiplatelet type) and ICH Score

Inclusion Criteria

Age ≥18 years
Non-traumatic supratentorial ICH confirmed by brain imaging
Glasgow Coma Scale score 8-15
Platelet transfusion could be initiated within 6 hours of symptom onset and within 90 minutes of diagnostic brain imaging
Use of antiplatelet therapy (COX inhibitor, ADP receptor inhibitor, or adenosine reuptake inhibitor) for ≥7 days pre-ICH
Pre-ICH modified Rankin Scale score 0-1

Exclusion Criteria

Epidural or subdural hematoma, or underlying aneurysm or AVM on imaging
Planned surgical evacuation of ICH within 24 hours
Intraventricular hemorrhage more than sedimentation in posterior horns of lateral ventricles
Previous adverse reaction to platelet transfusion
Known use of vitamin K antagonist (unless INR ≤1.3) or history of coagulopathy
Known thrombocytopenia <100×10⁹/L
Lacking mental capacity before ICH
Death appeared imminent

Arms

Field	Platelet Transfusion	Control
Intervention	Standard care plus platelet transfusion initiated within 6 hours of symptom onset and within 90 minutes of diagnostic brain imaging. Patients on COX inhibitor ± dipyridamole received 1 platelet concentrate; patients on ADP receptor inhibitor ± other antiplatelet received 2 platelet concentrates.	Standard care according to contemporary European and national guidelines, without platelet transfusion
Duration	Single transfusion	NA

Outcomes

Outcome	Type	Control	Intervention	HR / OR / RR	P-value
Functional outcome at 3 months rated using modified Rankin Scale (mRS 0-6), analyzed by ordinal logistic regression of the shift of all mRS categories	Primary	mRS distribution: 0=5.4%, 1=5.4%, 2=7.5%, 3=8.6%, 4=12.9%, 5=37.6%, 6=22.6%	mRS distribution: 0=3.1%, 1=4.1%, 2=4.1%, 3=16.5%, 4=14.4%, 5=25.8%, 6=32.0%	2.05	0.0114
Survival at 3 months	Secondary	72 (77.4%)	66 (68.0%)	0.62	0.15
mRS 4-6 (death or dependence) at 3 months	Secondary	52 (55.9%)	70 (72.2%)	2.04	0.0190
mRS 3-6 (poor outcome) at 3 months	Secondary	76 (81.7%)	86 (88.7%)	1.75	0.18
Median ICH growth at 24 hours (mL)	Secondary	1.16 (IQR 0.03-4.42)	2.01 (IQR 0.32-9.34)		0.81
Any Serious Adverse Event	Adverse	27 (29.0%)	41 (42.3%)	1.79	NS
Any Fatal SAE	Adverse	15 (16.1%)	24 (24.7%)	1.71	NS
SAE due to ICH complications	Adverse	13 (14.0%)	24 (24.7%)	2.02	NS
SAE due to thromboembolism	Adverse	1 (1.1%)	4 (4.1%)	3.96	NS
Transfusion reaction	Adverse	0 (0%)	1 (1.0%) - minor non-hemolytic

Subgroup Analysis

No significant interaction with treatment effect in pre-specified subgroups: single vs dual antiplatelet therapy, country of randomization (Netherlands vs France vs UK), and trichotomized baseline ICH volume (≤7mL vs >7-30mL vs >30mL). Sensitivity analysis excluding 36 protocol violations showed consistent results (adjusted OR 2.22, p=0.01).

Criticisms

Small sample size (n=190) relative to other acute stroke trials, resulting in some baseline imbalances
Baseline imbalances: platelet transfusion group had larger median ICH volume (13.1 vs 8.0 mL) but fewer with IVH extension (12.6% vs 21.7%)
Majority of participants used aspirin; relatively few on ADP inhibitors (clopidogrel) - limits generalizability to clopidogrel users
No screening logs maintained - potential selection bias
Antiplatelet adherence was self-reported; no platelet function testing performed
19% of participants (36/190) met at least one exclusion criterion (protocol deviations)
Open-label design (though outcome assessment was masked)
No clear mechanism identified to explain harmful effect of platelet transfusion
Unknown generalizability to low-middle income countries

Funding

Netherlands Organization for Health Research and Development (ZonMW, 170881002), Sanquin Blood Supply, Chest Heart and Stroke Scotland (CHSS project grant Ref. Res10), Le Programme Hospitalier de Recherche Clinique (PHRC)

Based on: PATCH (The Lancet, 2016)

Authors: Baharoglu MI, Cordonnier C, Al-Shahi Salman R, ..., Roos YB; on behalf of The PATCH Investigators

Citation: Lancet 2016;387(10038):2605-2613

Content summarized and formatted by NeuroTrials.ai.

PATCH

(2016)

Objective

To test whether platelet transfusion reduces death or dependence compared to standard care in patients with acute spontaneous intracerebral hemorrhage associated with antiplatelet therapy use

Study Summary

• Platelet transfusion WORSENED outcomes compared to standard care (adjusted OR 2.05 for worse mRS, p=0.01)
• Higher rates of death or dependence (mRS 4-6) with platelet transfusion: 72% vs 56%
• No reduction in hematoma growth with platelet transfusion

Intervention

Platelet transfusion (1 concentrate for COX inhibitor users, 2 concentrates for ADP inhibitor users) within 6 hours of symptom onset and 90 minutes of imaging

Inclusion Criteria

Age ≥18, supratentorial ICH on imaging, GCS 8-15, antiplatelet therapy ≥7 days pre-ICH (aspirin, clopidogrel, or dipyridamole), pre-ICH mRS 0-1, transfusion possible within 6h of onset

Study Design

Arms: Platelet transfusion + standard care vs Standard care alone

Patients per Arm: 97 vs 93

Outcome

• Primary: Adjusted OR 2.05 (95% CI 1.18-3.56, p=0.01) favoring standard care (platelet transfusion harmful)
• mRS 4-6: 72.2% vs 55.9% (OR 2.04, p=0.02)
• Mortality: 32% vs 23% (NS)

Bottom Line

Major Points

First randomized trial of platelet transfusion for acute ICH in patients on antiplatelet therapy
Platelet transfusion significantly worsened functional outcomes (adjusted OR 2.05, p=0.01)
72% of platelet transfusion group had mRS 4-6 vs 56% in standard care group
No significant reduction in hematoma growth with platelet transfusion
Findings consistent across subgroups (single vs dual antiplatelet, country, ICH volume)
Possible mechanisms of harm: pro-thrombotic effects, inflammation, impaired collateral perfusion
Trial stopped at pre-specified sample size, not for futility or harm

Study Design

Study Type: Randomized, open-label, masked endpoint (PROBE), phase 3 trial
Randomization: Yes
Blinding: Open-label for participants and treating clinicians; outcome assessors and data analysts masked to treatment allocation
Sample Size: 190
Follow-up: 3 months
Centers: 60
Countries: Netherlands, United Kingdom, France

Primary Outcome

Definition: Functional outcome at 3 months rated using modified Rankin Scale (mRS 0-6), analyzed by ordinal logistic regression of the shift of all mRS categories

Control	Intervention	HR/OR	P-value
mRS distribution: 0=5.4%, 1=5.4%, 2=7.5%, 3=8.6%, 4=12.9%, 5=37.6%, 6=22.6%	mRS distribution: 0=3.1%, 1=4.1%, 2=4.1%, 3=16.5%, 4=14.4%, 5=25.8%, 6=32.0%	2.05 (1.18-3.56)	0.0114

Limitations & Criticisms

Small sample size (n=190) relative to other acute stroke trials, resulting in some baseline imbalances
Baseline imbalances: platelet transfusion group had larger median ICH volume (13.1 vs 8.0 mL) but fewer with IVH extension (12.6% vs 21.7%)
Majority of participants used aspirin; relatively few on ADP inhibitors (clopidogrel) - limits generalizability to clopidogrel users
No screening logs maintained - potential selection bias
Antiplatelet adherence was self-reported; no platelet function testing performed
19% of participants (36/190) met at least one exclusion criterion (protocol deviations)
Open-label design (though outcome assessment was masked)
No clear mechanism identified to explain harmful effect of platelet transfusion
Unknown generalizability to low-middle income countries

Citation

Lancet 2016;387(10038):2605-2613

View Original Publication →

PATCH

PlAtelet Transfusion versus standard care after acute stroke due to spontaneous Cerebral Haemorrhage associated with antiplatelet therapy

Clinical Question

Bottom Line

Major Points

Design

Inclusion Criteria

Exclusion Criteria

Arms

Outcomes

Subgroup Analysis

Criticisms

Funding

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