Background
Phase 3, multicenter, randomized, partially blinded, Bayesian adaptive, noninferiority, storage duration-ranging trial at 27 sites in the US and Australia, December 2021 to March 2025. Pediatric and adult patients undergoing cardiac surgery with planned cardiopulmonary bypass who developed active bleeding requiring platelet transfusion. N=1000 transfused; 989 in the primary analysis (mean age 42.1 y, SD 30.1; 67.8% male). Platelets are conventionally stored at room temperature (20–24°C) for 5–7 days because of bacterial-contamination risk; cold storage (1–6°C) suppresses bacterial growth and may preserve or enhance hemostatic function, potentially allowing far longer dating and reducing wastage and shortages.
Results
Interventions and follow up: Arm A: Cold-stored platelets (CSP), 1–6°C, maximum 21 days of storage (n=650)
Arm B: Room-temperature platelets (RTP), 20–24°C, maximum 7 days of storage (n=339)
Randomization: 2:1 (CSP:RTP), adaptive across cold-storage durations
Primary endpoint: Intraoperative hemostatic efficacy score (1–5; higher = greater bleeding); noninferiority margin 1 point; success required ≥1 cold-storage duration of ≥7 days with posterior probability of noninferiority ≥97.5%
Secondary endpoint: 24-hour chest tube output
mFollow up: perioperative and in-hospital outcomes; duration NR
Results: Hemostatic efficacy score (primary): CSP noninferior to RTP at every cold-storage duration tested, posterior probability of noninferiority >99.9%
Pooled mean difference (CSP − RTP): 0.09 (95% credible interval −0.06 to 0.23)
Post hoc pooled score: 3.08 (SD 1.15) CSP vs 2.99 (SD 1.10) RTP
24-h chest tube output: median 8.9 mL/kg (IQR 5.2–15.4) vs 8.4 mL/kg (IQR 5.5–15.9); difference in medians 0.4 (95% CI −1.0 to 1.5), not significant
Surgical reexploration: increased in the CSP group (rate NR)
Arm B: Room-temperature platelets (RTP), 20–24°C, maximum 7 days of storage (n=339)
Randomization: 2:1 (CSP:RTP), adaptive across cold-storage durations
Primary endpoint: Intraoperative hemostatic efficacy score (1–5; higher = greater bleeding); noninferiority margin 1 point; success required ≥1 cold-storage duration of ≥7 days with posterior probability of noninferiority ≥97.5%
Secondary endpoint: 24-hour chest tube output
mFollow up: perioperative and in-hospital outcomes; duration NR
Results: Hemostatic efficacy score (primary): CSP noninferior to RTP at every cold-storage duration tested, posterior probability of noninferiority >99.9%
Pooled mean difference (CSP − RTP): 0.09 (95% credible interval −0.06 to 0.23)
Post hoc pooled score: 3.08 (SD 1.15) CSP vs 2.99 (SD 1.10) RTP
24-h chest tube output: median 8.9 mL/kg (IQR 5.2–15.4) vs 8.4 mL/kg (IQR 5.5–15.9); difference in medians 0.4 (95% CI −1.0 to 1.5), not significant
Surgical reexploration: increased in the CSP group (rate NR)
Adverse events
Venous or arterial thrombotic events: no difference between groups
Transfusion-associated adverse events: no difference
ARDS: no difference
Kidney failure / septic shock: no difference
Mortality: no difference
Reexploration for bleeding: higher with cold-stored platelets (the only between-group safety signal); numeric rates NR
Transfusion-associated adverse events: no difference
ARDS: no difference
Kidney failure / septic shock: no difference
Mortality: no difference
Reexploration for bleeding: higher with cold-stored platelets (the only between-group safety signal); numeric rates NR
Conclusions
In actively bleeding cardiac surgery patients on cardiopulmonary bypass, cold-stored platelets held for up to 21 days were noninferior to standard room-temperature platelets for hemostatic efficacy, with no difference in chest tube output, thrombosis, ARDS, renal failure, septic shock, or mortality. Extending platelet dating from 7 to 21 days would substantially reduce outdating and wastage and could allow platelet inventory at sites where the short room-temperature shelf life currently makes stocking impractical, including rural hospitals and prehospital settings. The higher reexploration rate in the cold-stored arm is the one discordant finding and warrants explanation before broad adoption.
Key Limitations
The primary endpoint is a subjective 1–5 surgeon-assessed hemostatic efficacy score, and the trial was only partially blinded, so assessment bias cannot be excluded. A 1-point noninferiority margin on a 5-point scale is wide relative to the observed between-group difference of 0.09, and the clinical meaning of a 1-point shift is not well anchored. The increased reexploration rate with cold-stored platelets is unexplained, was not the primary endpoint, and is clinically consequential. The 2:1 adaptive duration-ranging design means individual storage durations were tested with unequal and in places small numbers. The cohort mixes pediatric and adult patients (mean age 42.1 y with SD 30.1), limiting precision for either group separately. Findings apply to surgical bleeding on cardiopulmonary bypass and should not be extrapolated to prophylactic transfusion in hypoproliferative thrombocytopenia, where cold-stored platelets have shorter circulatory survival.
Clinical Context
Room-temperature storage with a 5- to 7-day shelf life has been the transfusion standard for decades and is the dominant driver of platelet wastage and of chronic supply shortages. Cold-stored platelets have re-entered US practice in limited fashion for actively bleeding patients under shortened dating, but randomized efficacy data at extended durations have been lacking; CHIPS is the first large phase 3 to test durations up to 21 days head to head. No regulatory change has been announced on the basis of this trial, and AABB standards and FDA guidance continue to govern permitted storage duration and indication. For hematologists, the practical implication is inventory and supply resilience rather than a change in transfusion thresholds; the reexploration signal should be tracked as further data emerge.