Platelet storage: a license to chill!

T he recent National Institutes of Health (NIH) State of the Science in Transfusion Medicine meeting, held in Bethesda, Maryland, in March 2015, revealed the alarmingly weak evidence base underpinning current practices in platelet (PLT) transfusion. As a scientific community, we do not know if prophylactic PLT transfusions before invasive procedures in patients with thrombocytopenia are effective. We have no high-quality data to guide PLT transfusion for patients with active bleeding, even though we understand that PLTs are absolutely vital to hemostasis. We currently base transfusion decisions on PLT counts rather than on function, despite substantial evidence of PLT dysfunction in bleeding trauma patients and the widespread use of anti-PLT drugs. Incredibly, with six decades of PLT transfusion history behind us, we have no standards for judging the in vitro or clinical hemostatic efficacy of PLT transfusion. This situation is all the more inexcusable given that we have acknowledged the loss of hemostatic and metabolic function over storage time, the so-called “PLT storage lesion,” since the very beginning of PLT transfusion therapy. Nevertheless, hard experience in cancer patients with thrombocytopenia, cardiac surgery patients with thrombocytopenia and PLT dysfunction from cardiopulmonary bypass, and more recently, military and civilian trauma patients teaches us that PLT transfusion is critical to hemostatic, lifesaving resuscitation. Unfortunately, as also highlighted at the NIH meeting, our collective ability to meet the needs of our bleeding patients is severely limited by the current 5day, 228C PLT storage paradigm. Storage at 228C was adopted because posttransfusion PLT recovery and survival, thought to be important in prophylactic transfusion by reducing donor exposure while maximizing the probability of PLT repair of damaged endothelium, was superior to that observed after refrigerated storage at 48C. Ironically, PLTs stored at 48C were known to be highly effective for acute hemostasis and obviously less vulnerable to bacterial contamination. In the end, 228C PLTs were adopted because of their perceived superiority for prophylaxis, while their hemostatic function was thought to be acceptable for bleeding patients. This decision was also driven by the logistic challenges faced by donor centers in managing two PLT inventories. A fundamental, and apparently flawed, assumption was made by pioneers in PLT transfusion in equating recovery and survival with “viability.” The unfortunate conflation of vital PLT functions like adhesion, aggregation, granule release, thrombin catalysis, and clot retraction with circulation time has left us struggling with the untenable proposition that the voluminous evidence of PLT decay during 228C storage can be ignored. Wishful thinking that PLTs miraculously recover lost function upon transfusion does not make it so. There are no clinical trial data documenting that such recovery occurs or that a dose–response relationship between current PLT products and hemostasis can be demonstrated. On the other hand, it has been clearly shown that 228C-stored PLTs, well known to lose aggregation responses to multiple agonists over storage, fail to reverse pharmacologic PLT inhibition. By contrast, 48C-stored PLTs, which maintain in vitro aggregation responses, are effective in restoring hemostatic function inhibited by aspirin. Loss of aggregation response has unquestionable clinical meaning both in the setting of anti-PLT therapy and in diagnosis of genetic PLT disorders. Thus, we have applied a “one-size-fits-all” storage solution, optimized to increase circulating PLT counts, to all patient populations without regard to their specific PLT function needs, such as acute hemostasis. In doing so, we have incurred enormous costs largely driven by the increased risk of bacterial growth in 228C PLTs: shorter shelf life means reduced availability of a lifesaving product; increased sepsis risk drives higher testing costs and reduced availability due to quarantine; a residual sepsis risk despite extensive and expensive testing undermines health system outcomes; requirements for dedicated incubators and agitators consume valuable blood bank space, power, and maintenance costs; reduced shelf life imposes greater burdens on donors and donor recruitment; reduced shelf life limits shipping of PLTs to smaller or outlying hospitals and clinics as well as the ability to resupply across state or international boundaries in times of emergency need; and reduced product efficacy due to the storage lesion drives waste. Counting PLTs is easy and following a daily PLT count simplifies inpatient rounds, but we The opinions or assertions contained herein are the private views of the author and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense. doi:10.1111/trf.13433 Published 2016. This article is a U.S. Government work and is in the public domain in the USA TRANSFUSION 2016;56;13–16