Red Blood Cell Mechanical Fragility as a Potential Predictor of Long-Term Hemolysis from Ventricular Assist Devices

Abstract

Introduction: Recent improvement in design and performance of Left Ventricular Assist Devices facilitate their use for destination therapy. The shear stresses in such devices can damage patients’ red blood cells (RBC), leading to increased hemolysis, which has been associated with pump thrombosis and patient mortality. Here we report an investigation assessing RBC mechanical fragility as a potential metric of blood damage and its potential utility in monitoring LVAD performance. Methods: Twenty subjects were recruited from the Center for Circulatory Support at the University of Michigan. Thirteen were implanted with the HeartWare HVAD (Medtronic, Inc.) and 7 with HeartMate 3® LVAD (HM3; Abbott Labs). Blood samples were obtained before surgery and at 1 hour, 24 hours, 1 week and 4 weeks after. Hemolysis biomarkers, total lactate dehydrogenase (LDH) and LDH isoenzymes, bilirubin, haptoglobin, and serum hemoglobin were determined through standard clinical tests. Mechanical fragility, as a metric of sub-hemolytic RBC damage, was determined using electromagnetically driven bead milling in a tube with a cylindrical bead, combined with non-invasive spectrophotometric analysis of induced hemolysis upon selected durations of the stress application. Certain variations of the stressing regime were employed for comparison. Results: RBC mechanical fragility, as assessed through some of the stress application regimes, was correlated with certain hemolysis metrics like bilirubin, LDH, and LDH1. Specifically, a subset of pre-surgery RBC mechanical fragility markers were strongly correlated with bilirubin levels measured 1 day, 1 week, and 1 month (though not immediately) after the surgery. While such correlation with unconjugated bilirubin declined in significance over time, the correlation to conjugated bilirubin reached significance at 1 month. Mechanical fragility values determined in albumin-supplemented medium at 1-day post-surgery, showed strong correlation to total LDH and LDH1 at 1-month post-surgery (p < 0.01, R2 up to 0.45), with the correlation with LDH1 stronger than with total LDH. Conclusions: These data demonstrate the potential for some RBC mechanical fragility metrics as predictive prognostic biomarkers for hemolysis induced by implantable circulatory support systems. With appropriate tailoring of testing parameters to best suit the application, mechanical fragility assays could help facilitate the transition to greater utilization of ventricular assist devices.