Development of a contact-free assay to evaluate stored blood quality using ultrasound viscoelasticity techniques

PROJECT SUMMARY
Blood transfusion is the most commonly performed hospital procedure, with over 11 million red blood cell (RBC)
units transfused each year in the United States alone. To accommodate time lags between blood donation and
transfusion, blood units are preserved and refrigerated until use. Current FDA guidelines limit the shelf life of
Adsol-preserved stored RBCs to 42 days. Beyond this window, efficacy of the transfusion product is thought to
be compromised. This is because storage alters the RBC membrane permeability and eventually leads to RBC
stiffening and loss of flexibility, irreversible sphericity, and a diminished ability to pass through the
microcirculation once transfused. Despite standard FDA guidelines, these adverse changes are known to
progress at varying rates and are thought to have a differential impact on transfusion outcomes in vulnerable
populations. Whether RBCs should be transfused after a 35-day limit is a topic of debate; however, substantial
evidence suggests that a tailored approach, accounting for the wide variation in RBC deterioration rates, should
be implemented rather than a universal expiration date. Blood has been described as a viscoelastic fluid, with
quantifiable elasticity, viscosity, and relaxation time that alter with storage age and with the proportion of stiffened
RBCs. However, the deterioration rates (e.g., stiffening) of RBCs vary widely by the blood donor, and storage
age alone is not a reliable indicator of RBC quality. Our group has been developing acoustic radiation force
impulse (ARFI) ultrasound, a promising approach for monitoring blood characteristics through sono-transparent
surroundings, such as polyvinylchloride blood bags. The advantage of a contact-free assay is two-fold: 1).
Human blood is a biohazard and exposure risks should be minimized, and 2). Sampling blood units by standard
techniques breaks the sterility of the blood bag, rendering the blood product unusable. A point-of-care, contact-
free assay to evaluate stored RBC quality prior to transfusion has the potential to transform clinical practice by
implementing a precision medicine approach to transfusion efficacy. Although shear wave elastography imaging
(SWEI) is a commercially available ultrasound technique for assessing viscoelasticity of solid tissues, it is not
amenable to anticoagulated blood because shear waves rapidly attenuate in fluid media. Unlike SWEI; however,
ARFI does not depend upon shear wave propagation, making it more suitable for the evaluation of fluids. In this
3-year project, we will accomplish the following: 1). Optimize the ARFI beam sequences to assess stored blood
viscoelascity, using ektacytometry (i.e., elongation index, a measure of bulk RBC deformability) and viscometry
as comparative references for ARFI metrics, 2). Validate the clinical relevance of ARFI viscoelasticity by
analyzing pre-transfusion ARFI metrics and post-transfusion hemoglobin increment, in an observational study
enrolling 50 study participants undergoing clinically indicated RBC transfusion, and 3). Compare ARFI metrics
versus storage age as predictors of transfusion outcomes.

Grant Number: 5R21EB035312-04
NIH Institute/Center: NIH
Principal Investigator: MELISSA CAUGHEY