Editorial
An Oasis in the Platelet Desert?
Matthew D. Neal, Philip C. Spinella, Lucy Z. Kornblith
JAMA Published Online: December 8, 2025
doi: 10.1001/jama.2025.24442
A substantial proportion of the global population lacks reliable, timely access to platelet transfusions, largely due to constraints in donor supply and the inherently short shelf life of platelets. Even in high-income countries, including the US, platelet availability remains limited, as an aging donor population is not being sufficiently replenished by younger donors. As a result, the platelet supply is increasingly at risk of failing to meet clinical demand, particularly for cardiac surgery, the management of hypoproliferative thrombocytopenia in oncology patients, and the treatment of patients with acute or chronic bleeding disorders—needs that are all expected to rise as the population ages.1
The requirement to store platelets at room temperature, combined with their limited 5- to 7-day shelf life, further constrains availability. In high-income countries, hospitals with low utilization rates, such as rural or nontertiary care hospitals, often cannot maintain platelet inventories because the likelihood of product expiration and waste is prohibitively high.2 These gaps in access have resulted in so-called platelet deserts. Importantly, platelet deserts can also arise in other high-resource systems under specific operational conditions. For example, deployed military hospitals frequently face severe platelet shortages that limit their ability to treat bleeding due to combat injuries. At a global level, platelet deserts are most prevalent in low- and middle-income countries, where systemic supply constraints and limited storage capacity deprive the world’s most vulnerable populations of timely, lifesaving platelet transfusions that are necessary due to bleeding after surgery, trauma, gastrointestinal hemorrhage, or peripartum complications.
Hemostatic resuscitation research has demonstrated that platelets may save lives when given early,3,4 and international guidelines support early platelet transfusion in bleeding patients.5 As such, a rapidly evolving area of investigation involves the search for an “oasis in the platelet desert”—a product that works at least as well as room temperature–stored liquid platelets to stop bleeding but that does not have the same storage limitations and risk of wastage, allowing access in remote and austere environments.
In this issue of JAMA, Reade and colleagues6 provide data from a randomized clinical trial testing one such candidate product. The Cryopreserved vs Liquid Platelets II (CLIP-II) trial was a randomized, double-blind, multicenter, parallel-group, noninferiority trial that tested platelets cryopreserved in dimethyl sulfoxide (DMSO) compared with liquid-stored platelets for bleeding after cardiac surgery. CLIP-II was designed based on the observations from CLIP-I7 and other small randomized and observational studies that suggested cryopreserved platelets not only overcome the storage limitations of room temperature–stored liquid platelets, but also have a potential for greater hemostatic efficacy. A noninferiority design was chosen due to the advantages of a product with greater availability, and patients with a high risk of requiring platelet transfusion were enrolled. Patients were given up to 3 units of study platelets, after which open-label use of room temperature–stored liquid platelets was permitted. The primary outcome was surgical chest drain output in the first 24 hours after intensive care unit admission, with secondary, tertiary, and safety outcomes including mortality, thrombosis, transfusion requirements, and length of stay.
Although there was no statistically significant difference between chest drain output between groups, the noninferiority of cryopreserved platelets could not be established for the primary outcome because the confidence intervals extended beyond prespecified thresholds. The higher absolute volume of surgical chest drain output in the cryopreserved platelet group aligns with multiple secondary outcomes suggesting that bleeding was worse in patients who received cryopreserved platelets. Most secondary and tertiary outcomes related to hemostasis and transfusion were significantly worse in the cryopreserved platelet group, and the increase in blood loss may have been as high as 34%.
A major concern in the present trial is the presence of unblinding. Twenty five percent of patients in the cryopreserved platelet group received open-label, room temperature–stored liquid platelets after the first study cryopreserved platelet unit but before all 3 study units were transfused. This dwarfs the 3.1% open-label transfusion rate in the liquid platelet group and may threaten the integrity of the trial due to bias from unblinding. The reasons for these transfusions are unknown. However, given the overall poor performance of cryopreserved platelets compared with room temperature liquid platelets in bleeding indices, the potential of the treating clinician to react to worsening bleeding with open-label use of their standard product exists. The dilution of cryopreserved platelets with room temperature liquid platelets may have reduced observed differences between the study groups. If there was higher adherence to using cryopreserved platelets, it is possible that there may have been even worse bleeding in the cryopreserved platelet group.
The reasons for the apparent conflict in results between CLIP-II, CLIP-I, and prior studies of cryopreserved platelets are not immediately apparent. The authors note that in at least 1 prior study8 in which cryopreserved platelets had improved hemostatic effects, there was a difference in the preparation of the cryopreserved platelets such that the DMSO preservative was washed. DMSO preservation of platelets may induce toxicity to function and destruction of cells,9 and it is likely that the methods of processing to include washing may affect the final hemostatic function of the product.
An important question remains in the context of platelet deserts. Even if cryopreserved platelets are inferior to room temperature–stored liquid platelets, which we conclude from the present study, are they better than no platelets at all? In other words, in scenarios where room temperature–stored liquid platelets are not available, could cryopreserved platelets be an option? Reade and colleagues opine this may be the case based on their interpretation of an overall favorable safety profile of cryopreserved platelets. However, the numerically higher absolute risk of mortality, reoperation, infectious complications, and longer duration of mechanical ventilation and intensive care unit and hospital stays in the cryopreserved platelet group raise concerns about the true safety of the product. This, combined with the limitations in power of the present study along with the increased bleeding indices in the cryopreserved platelet group, leaves us with limited enthusiasm for this specific product. These cryopreserved platelets may be more of a mirage than an oasis.
Research around platelet products and substitutes is rapidly evolving, and we believe likely represents the single greatest area of opportunity in bleeding control in the coming years. Of great interest and relevance to the findings of the CLIP-II trial will be the results of another cryopreserved platelet trial, the DMSO Cryopreserved Platelets in Cardiopulmonary Bypass Surgery (CRYPTICS; NCT04709705) randomized trial.10 Although data are not yet publicly available, the trial was reportedly terminated early by an independent data monitoring committee due to meeting a primary end point of noninferiority as reported at the 2025 Association for the Advancement of Blood & Biotherapies annual symposium.11 Examination of these results alongside CLIP-II will be critical, as will understanding differences in the products, processing, and patient population.
Additional strategies to address the challenges of platelet deserts are also underway. Cold storage of platelets at 4 °C has recently been shown to be feasible and safe in trauma, both in hemorrhagic shock12 and traumatic brain injury.13 Cold storage can extend shelf life from 5-7 days to 21 days and may enhance access to platelets at hospitals with lower utilization rates, which is likely to reduce waste. However, efforts to further increase the shelf life and remove cold chain storage requirements in remote or far forward locations (particularly relevant to military applications and large-scale combat operations) are needed. These currently include lyophilized platelet–derived products14 and synthetic strategies. Both have the potential advantage of extended storage duration and portability without cold chain requirements. Lyophilized platelets are currently in human trials (NCT05771831). Synthetic platelet mimicry, while still in a preclinical phase, may address additional challenges associated with donor dependency, scale, and storage of donor-derived platelets.15 Together, these and other advances on the cutting edge of hemostasis and transfusion carry great promise that an oasis may be on the horizon and that a solution to the public health crisis of platelet access may soon come.
