Cold-stored platelets maintained noninferior hemostatic efficacy compared with conventional room-temperature platelets in patients undergoing cardiac surgery with cardiopulmonary bypass, even after storage for up to 21 days. However, patients receiving cold-stored platelets had higher rates of surgical reexploration for bleeding and received greater volumes of blood products.
The phase 3 Chilled Platelet Study (CHIPS) was a multicenter, randomized, partially blinded, adaptive noninferiority trial conducted at 27 sites in the US and Australia from December 2021 to March 2025. Investigators evaluated pediatric and adult patients undergoing complex cardiac surgery with planned cardiopulmonary bypass and anticipated bleeding requiring platelet transfusion. Of 1,811 randomized patients, 1,000 received platelet transfusions, including 660 in the cold-stored platelet and 340 in the room-temperature platelet group. The primary efficacy analysis included 989 patients, of whom 650 received cold-stored platelets and 339 received room-temperature platelets. The mean age was 42.1 years, and 67.8% were male.
Patients were randomized in a 2:1 ratio to receive cold-stored platelets maintained at 1°C to 6°C for up to 21 days or conventional platelets stored at 20°C to 24°C for up to 7 days. The primary outcome was a 5-level hemostatic efficacy score assessing bleeding during the 24 hours following the first platelet transfusion, with higher scores indicating greater bleeding. The prespecified noninferiority margin was 1 point, and the trial required a posterior probability of noninferiority of at least 97.5% for at least 1 cold-storage duration of 7 days or longer. The secondary outcome was chest tube output at 24 hours.
Cold-stored platelets met the primary noninferiority criterion at every evaluated storage duration through 21 days, with a posterior probability exceeding 99.9%. Pooled across storage durations, the estimated mean hemostatic efficacy score was 3.08 in the cold-stored group compared with 2.99 in the room-temperature group, representing an estimated difference of 0.09 points. No cold-storage duration demonstrated superiority over conventional storage.
There was no statistically significant between-group difference in the secondary outcome. Median chest tube output at 24 hours was 8.9 mL/kg among patients receiving cold-stored platelets compared with 8.4 mL/kg among those receiving room-temperature platelets, a difference of 0.4 mL/kg. Increasing the storage duration of cold-stored platelets to 21 days did not appear to affect chest tube output.
Prespecified subgroup analyses demonstrated consistent noninferiority across all evaluated patient groups, including different age categories, patients who had received antiplatelet agents within 7 days of enrollment, and those receiving ABO-incompatible or pathogen-reduced platelets. The primary outcome also did not differ statistically across platelet manufacturing methods. A per-intervention analysis produced findings similar to those of the primary analysis.
Despite comparable hemostatic efficacy, several exploratory outcomes differed between groups. Reexploration for bleeding within 24 hours of the first platelet transfusion occurred in 28 of 660 patients (4.2%) receiving cold-stored platelets compared with 6 of 340 patients (1.8%) receiving room-temperature platelets, an absolute difference of 2.5 percentage points. Patients in the cold-stored group also received greater volumes of total blood products, red blood cells, plasma, and platelets at 24 and 72 hours after intensive care unit admission.
Platelet count increases at 6 and 24 hours following the initial transfusion were greater in the room-temperature group. Cold-stored platelets may have been removed from circulation more rapidly or incorporated into clots at sites of active bleeding, potentially contributing to lower circulating platelet counts. These differences may have influenced subsequent transfusion decisions, although the authors acknowledged that lower hemostatic efficacy of cold-stored platelets could also explain the increased blood product use.
Exploratory safety analyses identified no statistically significant differences in arterial or venous thrombotic events, transfusion-associated adverse events, acute respiratory distress syndrome, kidney failure, septic shock, or mortality. Arterial thrombotic events occurred in 2.6% of patients receiving cold-stored platelets vs 3.8% receiving room-temperature platelets, while venous thrombotic events occurred in 2.6% vs 1.8%, respectively. Kidney failure occurred in 6.2% vs 6.8%, and 28-day mortality was 3.2% vs 1.8%.
Platelet transfusion indications were not standardized, potentially including patients who may not have benefited from transfusion and biasing the findings toward noninferiority. Some patients received both platelet types because of protocol deviations and inventory limitations, which may also have favored noninferiority. Additionally, modifications to the hemostatic efficacy score for patients weighing 50 kg or less had not been validated, and transfusion thresholds for blood components and other interventions were not standardized. The authors emphasized that the findings should be interpreted within the context of existing platelet transfusion practices in patients undergoing complex cardiac surgery.
The findings support cold storage as a potential approach to extending platelet availability for active bleeding, particularly in hospitals unable to maintain conventional platelet inventories because of their limited shelf life. However, the increased reexploration rates and blood product requirements in the cold-stored group remain important considerations.
“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,” wrote lead study author Philip C. Spinella, MD, of the University of Pittsburgh, and colleagues.
Disclosures: The study was funded by the Defense Health Agency. Several authors reported grants, consulting fees, or other financial relationships with pharmaceutical, medical device, and blood product companies.
Source: JAMA
