Hemolysis Testing In Vitro: A Review of Challenges and Potential Improvements

Abstract

Many medical devices such as cardiopulmonary bypass systems, mechanical heart valves, or ventricular assist devices are intended to come into contact with blood flow during use. In vitro hemolysis testing can provide valuable information about the hemocompatibility of prototypes and thus help reduce the number of animal experiments required. Such tests play an important role as research and development tools for objective comparisons of prototypes and devices as well as for the extrapolation of their results to clinical outcomes. Therefore, it is important to explore and provide new ways to improve current practices. In this article, the main challenges of hemolysis testing are described, namely the difficult blood sourcing, the high experimental workload, and the low reproducibility of test results. Several approaches to address the challenges identified are proposed and the respective literature is reviewed. These include the replacement of blood as the "shear-sensitive fluid" by alternative test fluids, the replacement of sparse, manual sampling and blood damage assessment by a continuous and automated monitoring, as well as an analysis of categories and causes of variability in hemolysis test results that may serve as a structural template for future studies.

In-vitro and In-vivo Feasibility Study for a Mobile VV-ECMO and ECCO2R System

“…The prototype status of the oxygenator may have caused a significant increase in hemolysis, because the entire casing was printed. Recently, Petersdorff-Campen et al [32] showed an increase in hemolysis in printed blood pumps of 620 %, which may explain our results. Last, we have successfully used a mobile gas blender that allows quick, individual, and automatable gas mixtures of medical oxygen and ambient air.…”

A reflection on ‘Protein coronas suppress the hemolytic activity of hydrophilic and hydrophobic nanoparticles’

“…30 Challenges for the translatability of nanomaterials between in vitro and in vivo applications include issues with stability, activity, and biocompatibility of nanomaterials. 31 The interplay of hemolysis and protein corona formation can contribute to this discrepancy between in vitro and in vivo studies. 32 Mailänder and co-workers compared the protein corona profile between coronas formed in mouse blood and in vivo .…”

Chitosan-Based Hemostatic Hydrogels: The Concept, Mechanism, Application, and Prospects

“…Studies have shown that hemolysis is a major challenge to the preparation of hemocompatible hemostatic materials [ 82 , 83 , 84 , 85 ]. Therefore, the hemocompatibility of a hemostatic material is evaluated by the degree of erythrocyte lysis and hemoglobin dissociation.…”