Are Cold-stored Platelets Inferior to Room-temperature?

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Purpose of the Chilled Platelet Study (CHIPS)

Researchers have published the results of the Chilled Platelet Study (CHIPS) in JAMA. This trial aimed to, “determine the maximum duration of cold storage, up to 21 days, for which cold-stored platelets (CSPs) are noninferior or superior in hemostatic efficacy to standard room-temperature platelets (RTPs) [stored up to seven days] when transfused in actively bleeding pediatric and adult patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). This study is a “phase 3, multicenter, randomized, partially blinded, adaptive, noninferiority, storage duration–ranging trial.”

Eligible patients [were required to be] no younger than 28 days of age and no older than 85 years of age. Exclusion criteria described by authors included, “known bleeding disorder, planned postoperative extracorporeal membrane oxygenation, ventricular assist device and/or continuous kidney replacement therapy, platelet transfusion within 24 hours, and thrombocytopenia (platelet count <75 ×10⁹/L). [Patients were] randomized after consent to receive CSPs versus RTPs in a 2:1 ratio.”

The researchers explained that, “the indication for platelet transfusion was clinician dependent and therefore pragmatic. The intervention period, when the patient could receive study platelet infusions, extended 24 hours after the first infusion. Initially, the two trial study treatments were RTPs and CSPs stored for up to 7 days. Then, at each planned interim analysis, the maximum storage duration for CSPs was to be increased (or decreased if increased earlier and subsequent data were less promising) up to a maximum possible storage duration of 21 days, according to a prespecified algorithm and the bayesian posterior probability of noninferiority at each cold-storage duration.”

Additionally, they noted that the U.S. Food and Drug Administration (FDA) issued “guidance permitting CSP use stored up to 14 days for active bleeding when RTPs were not available or practical” during the trial after 280 individuals had been enrolled in CHIPS. “At trial initiation, the maximum allowed dose of CSPs was six units or six 15-mL/kg pediatric doses. At the 600-patient interim analysis, the maximum dose was increased to eight units or eight pediatric doses based on safety data and the need to reduce use of RTPs in the CSP group for patients needing more than the maximum allowed dose.”

The authors wrote that the study’s primary outcome was, “5-level ordinal hemostatic efficacy score adapted from the universal definition for perioperative bleeding score, with values ranging from 1 to 5 and higher values indicating greater bleeding. [The one secondary] outcome measure was 24-hour total chest tube output (mL/kg). This secondary outcome was only evaluated for superiority.” CHIPS took place from December 2021 to March 2025, and platelets were transfused “to 660 patients in the interventional CSP group and 340 patients in the standard-of-care RTP group. [There were 989 patients included in the primary analysis, with 650 in the CSP group and 339 in the RTP group.]”

Findings

The researchers found that, “[t]he posterior probability that CSPs were noninferior to RTPs on the primary outcome was greater than 99.9 percent for all durations up to and including 21 days. If CSPs were pooled across storage durations, the mean of the primary outcome was 3.08 (95 percent credible interval [CrI], 2.99-3.17) versus RTPs of 2.99 (95 percent CrI, 2.88-3.11) for a difference of 0.09 (95 percent CrI, −0.06 to 0.23). For the primary outcome, no storage duration of CSPs was statistically superior to RTPs. [Within all subgroups] analyzed, CSPs were noninferior to RTPs for the primary outcome.” Additionally, the study found that, “increasing the storage age of CSPs to 21 days did not appear to affect 24-hour chest tube output. [There were no] differences in venous or arterial thrombotic events, transfusion-associated adverse events, acute respiratory distress syndrome, kidney failure, septic shock, and mortality between the study groups, except for increased re-exploration rates in the CSP group.”

CHIPS Conclusions

The paper concluded that, “CSPs stored for up to 21 days were noninferior to RTPs stored up to 5 to 7 days for the primary outcome of the hemostatic efficacy score based on a noninferiority margin of one point, with a greater than 99.9 percent posterior probability of noninferiority. Platelet supply is often not sufficient to meet demand, and many hospitals cannot maintain RTP inventory due to their short shelf life. Utilizing CSPs with a storage duration to 21 days, for use in the treatment of active bleeding, has the potential to reduce waste and shortages and increase platelet availability where they cannot be currently kept in inventory due to the short storage duration of RTPs transfused in this study.” Limitations of the paper acknowledged by the authors were: “[t]here was no standardized indication for platelets, which may have led to the inclusion of patients who may not have benefited from a platelet transfusion, thereby biasing the entire cohort toward noninferiority; 11 patients were excluded from the primary analysis for receiving treatments that made calculation of cold-storage duration impossible or for missing primary outcomes; other participants in both groups received mixtures of CSPs and RTPs, which may have biased the trial results toward demonstrating noninferiority; despite the trial methods requiring both RTPs and CSPs to be in inventory on the day of surgery, delays in shipping times, allocation of the wrong product from the blood bank, and exhaustion of the blood bank inventory of the study product led to nonadherence to the randomized intervention.”

Editorial

An accompanying editorial titled “A World With Platelets Stored Cold for 21 Days Chill and Tender” explained that the CHIPS results, “herald a possible revolution in the availability, safety, and cost of an essential medical therapy.” The editorial highlighted that, “RTP production is expensive, fragile, and complicated, with a frustrating combination of a high wastage rate and short supply. Additionally, historically, RTPs were developed to meet the needs of patients with cancer from an early era of chemotherapy. However, CHIPS provides high-quality evidence that CSPs stored for 21 days achieve clinical results that are noninferior to conventional RTPs.” The author concluded the editorial by explaining that, “[p]latelets are an essential medical therapy, and CHIPS is only the first major trial of CSPs. More trials are needed, particularly studying prophylactic uses in cancer, but also in other therapeutic contexts, such as trauma and liver transplant. [Many of these studies] are already being planned and prepared. If CSPs are proven to be a real alternative to RTPs in these situations, then we may be able to provide more platelets to patients who need them and, maybe, astonishingly, with greater ease and security and at less risk and cost.”

Citations: Spinella, P.C. Zantek, N.D. VanBuren, J.M. et al. “Cold and Room-Temperature Platelets in Cardiac Surgery: The CHIPS Randomized Clinical Trial.”

JAMA. 2026 Hess, A.S. “A World With Platelets Stored Cold for 21 Days: Chill and Tender.” JAMA. 2026.