The Storage Lesion
Early this year I discussed the potential implications of the “storage lesion” for RBC transfusions in a previous blog post, The Storage Lesion, Soldier On and Stay Tuned. Several studies were cited and questions put forth that remained with the conclusion to soldier on and stay tuned. Recently there have been publications that provide additional information, which continue to fuel the fire surrounding the controversy of “fresh” vs. “old” blood. Let’s revisit these original questions and see where the literature is today.
One of the initial questions was whether or not there is clear evidence that “older” RBC units fail to provide adequate tissue oxygenation in vivo and thus are associated with adverse outcomes. Two recent studies have some very interesting findings. Heddle et al. (INFORM-P Study) report on a single-site random controlled trial (RCT) involving over 900 patients in which the mortality was slightly increased in those patients receiving “fresh” RBC units1. This was intended to be a pilot study of the feasibility of a larger well-powered RCT, but certainly provides a surprising finding. Similarly, the ABLE Study showed a slight increase in mortality in the “fresh” group, but confidence intervals were high and this too was intended to be a pilot study2. The just-published ARIPI Study found no significant adverse outcomes in stable pediatric ICU patients when utilizing “older” RBCs for transfusion3. Yet the meta-analysis just completed by Wang and colleagues found the relative risk of death associated with older blood to be as high as 16%4. Data from the RECESS Study and the NIH study of RBC units used in CVS are yet to be completed5,6.
Another important question was how the age of blood should be defined. The above-mentioned studies continue to feed this frenzy as well, given that the age of RBCs is different in each study. The INFORM-P characterized fresh vs. old as 12d vs. 26 days on average and the ABLE Study utilized <8d as the definition of fresh units. Aubron et al. comment in their publication that three studies imply a 14-day “rule” yet their two-site RCT utilized 12d vs. 23 day definitions plus or minus several days7. This suggests to me that we have not gotten our arms around this issue. And, what is so “magical” about one date vs. another? Is there truly a specific day beyond which the RBCs begin their ultimate demise? Keep in mind that these studies also differ in the RBC storage solutions, leukoreduction, patient subsets with multiple comorbidities and the analytics. These differences in study design beg the next questions: Is there possible recovery of RBC function when transfused into an individual patient’s intravascular milieu? Are only certain patients at risk for the purported effects of this storage lesion?
The remaining questions apply to the ethics of transfusion and stewardship of this resource. Until the storage lesion is truly and adequately defined in terms of its exact mechanism and affects, how are we to proceed within our facilities and communities? Are we to arbitrarily assign certain patient subsets to receive older vs. fresher units based on our own definitions? Those patients with blood group B and AB will, by nature of availability, likely receive “older” units. And certainly our more critical patients that absolutely and appropriately may necessitate transfusion could be exposed more frequently to “older” units as a result of inventory issues.
So the bottom line is that even with these recently published studies, we are not necessarily any closer to an answer than we were in early 2012. I can only reiterate the same message as before: soldier on and stay tuned because the saga continues!