CHIP trial extends shelf life compared with conventional room-temperature storage

Key Takeaways

• A randomized trial tested cold-stored platelets for treatment of active bleeding in people undergoing complex cardiac surgery.
• These cold-stored platelets stayed effective out to 21 days in meeting noninferiority criteria for hemostatic efficacy against standard room-temperature platelets.
• The clinical implication is that cold-stored platelets can be used safely and effectively, and the longer shelf life is an answer to shortages and waste.

Extending the shelf life of platelets with refrigeration didn’t hurt their hemostatic function for people undergoing complex cardiac surgery, the landmark CHIPS trial found.

Platelets stored at 1-6°C (33.8-42.8°F) for up to 21 days were noninferior to platelets stored up to 7 days at room temperature in terms of control of active surgical bleeding in the 1,000-person trial. Hemostatic efficacy scores, on a scale of 1 to 5, were virtually the same between cold and room temperature platelet storage groups (3.08 vs 2.99; mean difference 0.09, 95% credible interval [CrI] -0.06 to 0.23; probability of noninferiority greater than 99.9%).

In addition, median chest tube output at 24 hours was comparable between cold storage and room temperature platelets (8.9 vs 8.4 mL/kg, difference 0.4, 95% CI -1.0 to 1.5). There were also no significant differences in thrombotic events, morbidity, or mortality outcomes between study groups, reported researchers led by Philip Spinella, MD, of the University of Pittsburgh.

“Use of CSPs [cold-storage platelets] may allow for increased availability of platelets by reducing wastage and shortages and may allow for incorporation of platelets into inventory at locations where platelets cannot be maintained due to the 5- to 7-day shelf life of RTPs [room-temperature platelets],” study authors wrote in JAMA.

Indeed, in the current era, approximately 10-20% of platelets expire before use.

With CHIP, the pendulum thus swings back to favor cold-stored platelets. Refrigeration had been the norm for storing platelets, which were used primarily for active bleeding, until studies dating back to around 1970 showed better post-transfusion recovery if the units had been stored at room temperature.

Renewed interest in cold-stored platelets was driven by military and trauma systems with a need for immediate bleeding control, and the FDA has already responded by allowing for platelets in cold storage up to 14 days to be used in active bleeding, explained Anthony Estrera, MD, and Charles Miller III, PhD, both of McGovern Medical School at UTHealth Houston.

“The [CHIP] findings are noteworthy because they challenge a storage paradigm that has remained largely unchanged for more than 5 decades. Although CSP recipients experienced lower posttransfusion platelet count increments and somewhat greater use of blood products, these differences did not translate into worse clinical hemostatic outcomes,” Estrera and Miller wrote in an accompanying editorial in JAMA Surgery.

“The overall message is clear: refrigerated platelets retained clinical effectiveness for managing hemostasis in cardiac surgery patients, despite storage periods nearly 3 times longer than conventional RTPs,” they stressed.

CHIPS was a phase III partially blinded trial conducted at 27 sites in the U.S. and Australia. Included were 989 adults and children undergoing cardiac surgery with cardiopulmonary bypass. Participants were randomized 2:1 to cold-stored platelets or room-temperature platelets, with no standardized indication for platelets.

The study cohort averaged 42.1 years of age, and two-thirds of participants were male. Preintervention platelet counts were just over 100×10⁹/L. During surgery, median cardiopulmonary bypass time was 164 minutes.

Of note, Spinella and colleagues reported that the cold-stored platelets did not meet superiority criteria in CHIPS. Investigators could not show that any cold storage duration was statistically superior to room temperature storage regarding hemostatic efficacy.

Meanwhile, there was a higher rate of re-exploration for bleeding with cold-stored platelets (4.2% vs 1.8%). These blood products were also transfused in larger amounts at 24 and 72 hours after intensive care unit admission.

Spinella’s group had several theories to explain these findings. “CSPs may have been removed from circulation more rapidly than RTPs, which may also have led to differences in platelet count increments and influenced increased platelet transfusion,” they suggested.

“Another hypothesis for these findings is that increased platelet activation with cold storage may have led to increased platelet incorporation into clots at sites of active bleeding. As a result, fewer platelets would be circulating, leading to lower platelet counts in ex vivo assays and global hemostatic function in TEG [thromboelastography].”

The investigators cautioned that the study might have given platelets to people who were not necessarily going to benefit from them in the first place, thereby biasing the entire cohort toward noninferiority. And despite a protocol requiring both types of platelets to be in inventory on the day of heart surgery, there were shipping delays and inventory issues resulting in 14.7% nonadherence in the cold-storage group.

“A formal cost-effectiveness analysis would have strengthened the policy implications of the study and, ultimately, may be necessary to guide widespread adoption,” added Estrera and Miller. “However, the potential economic and logistical benefits are immediately apparent.”