Abstract
In transfusion medicine, there has been a decades-long debate about whether the age of stored red blood cells (RBCs) is a factor in transfusion efficacy. Existing clinical studies investigating whether older RBCs cause worse clinical outcomes have provided conflicting information: some have shown that older blood is less effective, while others have shown no such difference. The controversial results could have been biased by the vastly different conditions of the patients involved in the clinical studies; however, another source of inconsistency is a lack of understanding of how well and quickly stored RBCs can recover their key parameters, such as stiffness and ATP concentration, after transfusion. In this work, we quantitatively studied the stiffness and ATP recovery of stored RBCs in 37 °C human serum. The results showed that in 37 °C human serum, stored RBCs are able to recover their stiffness and ATP concentration to varying extents depending on how long they have been stored. Fresher RBCs (1–3 weeks old) were found to have a significantly higher capacity for stiffness and ATP recovery in human serum than older RBCs (4–6 weeks old). For instance, for 1-week-old RBCs, although the shear modulus before recovery was 1.6 times that of fresh RBCs, 97% of the cells recovered in human serum to have 1.1 times the shear modulus of fresh RBCs, and the ATP concentration of 1-week-old RBCs after recovery showed no difference from that of fresh RBCs. However, for 6-week-old RBCs, only ~70% of the RBCs showed stiffness recovery in human serum; their shear modulus after recovery was still 2.1 times that of fresh RBCs; and their ATP concentration after recovery was 25% lower than that of fresh RBCs. Our experiments also revealed that the processes of stiffness recovery and ATP recovery took place on the scale of tens of minutes. We hope that this study will trigger the next steps of comprehensively characterizing the recovery behaviors of stored RBCs (e.g., recovery of normal 2,3-DPG [2,3-Diphosphoglycerate]and SNO [S-nitrosation] levels) and quantifying the in vivo recovery of stored RBCs in transfusion medicine.
Highlights
Introduction According to the World HealthOrganization, 92 million units of blood are collected annually in 164 countries[1]
These results confirmed that stored Red blood cells (RBCs) are capable of recovering their shear modulus in human serum, and the recovery process was on the time scale of tens of minutes
The results provide quantitative evidence to answer the following questions: whether the stiffness and ATP of stored RBCs can recover in human serum and how storage duration causes differences in the recovery of stiffness and ATP concentration
Summary
Introduction According to the World HealthOrganization, 92 million units of blood are collected annually in 164 countries[1]. Regulations stipulated by the US Food and Drug Administration (FDA) and many other countries specify 42 days as the shelf life for stored RBCs3. This “gold standard” was established based on the criterion of posttransfusion RBC survival of 75% or higher after 24 h4, where posttransfusion RBC survival was measured by monitoring transfused RBCs labeled with 51Cr5. More than 40 clinical studies reported that the use of older RBCs was associated with a significantly increased risk of adverse complications after transfusion[8]. These studies examined the effect of RBC
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