Can Temperature Modulation be the Answer to Extending Platelet Shelf Life?

Wayne ZhaoBy Wayne Zhao, PhD Student, Devine Lab

For every 25 units of platelets collected, 1 unit will be thrown away due to expiration or storage induced lesions.1 This wastage costs our health care system approximately 5 million dollars a year. The most common cause of having to discard units is the short storage life of platelet concentrates (PCs). Researchers have proposed an alternative storage condition for platelets in the hopes of extending platelet shelf life.

PCs are given primarily to two groups of patients. The first comprise patients with cancer who are undergoing chemotherapy, and consequently develop low platelet levels (thrombocytopenia) due to the drugs suppressing bone marrow production of platelets. PCs are transfused as often as once every two weeks to boost their platelet counts. The second group comprises patients who are actively bleeding due to a variety of reasons (e.g., post-surgery, trauma, obstetrical complications, gastrointestinal lesions) and in whom PC transfusions may help in achieving hemostasis.

Currently, PCs are stored at room temperature (22°C) under constant agitation. There are several problems associated with this storage condition, including a limited shelf life (7 days), a risk of bacterial growth, and a progressive decrease in their quality, the latter referred to as “storage lesion”. To solve these challenges, researchers are investigating the alternative of storing platelets under hypothermic conditions (4°C). Storing platelets in cold temperatures slows down microorganism growth, and may increase PC shelf life. Furthermore, platelet haemostatic activity is superior in cold-stored platelets (CT) compared to room temperature stored platelets (RT).2 The CT storage method was widely practiced from the 1960s until the 1980s. However, the protocol was replaced by RT storage after it was found that CT alters platelet structure, morphology, and activation characteristics, resulting in short post-transfusion circulation survival in patients.

From previously published work, researchers discovered, using murine models, that some of the cold induced damage to platelets, such as morphologic changes and cell surface glycoprotein clustering, could be reversed by re-warming the platelets and limiting CT storage to less than 18 hours.3 From this, a method was proposed whereby platelet storage temperatures are cycled (TC) between 4°C for 11 hours and 37°C for 1 hour. They hypothesized that any cold induced damage would be reduced during the 1 hour at 37°C. In subsequent murine models, TC stored platelets exhibited superiority with respect to in vitro platelet properties and in vivo recovery compared to CT platelets and RT platelets.4

In a study published in the November issue of Transfusion, Vostal, J et al. further investigated the TC method by conducting a clinical trial to test the in vivo recovery and survival of TC platelets compared RT and CT platelets in healthy human volunteers. Stored platelets were radiolabelled, transfused into the volunteers, and the recovery and survival of the platelets were monitored. Similar to the murine model, TC platelets had better in vivo recovery and survival compared to CT platelets.

In comparison to RT platelets, however, TC platelets had significantly lower recovery and reduced survival, which was inconsistent with the murine model. The authors speculated that the reasons for this disparity might be attributable to experimental design, platelet handling, and the small sample size (n=10). The authors proposed that TC platelets would be most effective in treating actively bleeding patients who do not require significant prolongation in platelet survival time.

Temperature modulation is just one of the important factors that contribute to the outcome of stored platelets. While this paper provided a glimpse into the complexity of platelet storage and preservation, further procedural development is needed to improve the in vivo survival and recovery of CT platelets.

  1. Collins, R. A., Wisniewski, M. K., Waters, J. H., Triulzi, D. J., & Yazer, M. H. (2015). Effectiveness of multiple initiatives to reduce blood component wastage. American Journal of Clinical Pathology, 143(3), 329–335. https://doi.org/10.1309/AJCP42WMHSSTPHXI
  2. Nair, P. M., Pandya, S. G., Dallo, S. F., Reddoch, K. M., Montgomery, R. K., Pidcoke, H. F., Ramasubramanian, A. K. (2017). Platelets stored at 4°C contribute to superior clot properties compared to current standard-of-care through fibrin-crosslinking. British Journal of Haematology, 178(1), 119–129. https://doi.org/10.1111/bjh.14751
  3. McGill, M. (1978). Temperature cycling preserves platelet shape and enhances in vitro test scores during storage at 4 degrees. The Journal of Laboratory and Clinical Medicine, 92(6), 971–82. Retrieved from http://europepmc.org/abstract/MED/739175
  4. Xu, F., Gelderman, M. P., Farrell, J., & Vostal, J. G. (2013). Temperature cycling improves in vivo recovery of cold-stored human platelets in a mouse model of transfusion. Transfusion, 53(6), 1178–1186. https://doi.org/10.1111/j.1537-2995.2012.03896.x

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