Modelling of Red Blood Cell Morphological and Deformability Changes during In-Vitro Storage

Nadeeshani Geekiyanage,Yuantong Gu,Robert Flower,Emilie Sauret,Suvash Saha

doi:10.3390/app10093209

Abstract

Storage lesion is a critical issue facing transfusion treatments, and it adversely affects the quality and viability of stored red blood cells (RBCs). RBC deformability is a key indicator of cell health. Deformability measurements of each RBC unit are a key challenge in transfusion medicine research and clinical haematology. In this paper, a numerical study, inspired from the previous research for RBC deformability and morphology predictions, is conducted for the first time, to investigate the deformability and morphology characteristics of RBCs undergoing storage lesion. This study investigates the evolution of the cell shape factor, elongation index and membrane spicule details, where applicable, of discocyte, echinocyte I, echinocyte II, echinocyte III and sphero-echinocyte morphologies during 42 days of in-vitro storage at 4 °C in saline-adenine-glucose-mannitol (SAGM). Computer simulations were performed to investigate the influence of storage lesion-induced membrane structural defects on cell deformability and its recoverability during optical tweezers stretching deformations. The predicted morphology and deformability indicate decreasing quality and viability of stored RBCs undergoing storage lesion. The loss of membrane structural integrity due to the storage lesion further degrades the cell deformability and recoverability during mechanical deformations. This numerical approach provides a potential framework to study the RBC deformation characteristics under varying pathophysiological conditions for better diagnostics and treatments.

Highlights

A red blood cell (RBC) transfusion is a critical and lifesaving medical procedure for anaemia caused by disease leading to inadequate bone marrow production or increased red blood cells (RBCs) breakdown, or by blood loss due to trauma or surgery [1,2,3,4]
This paper proposes a numerical approach inspired from the previous research for RBC morphology predictions [74,75,76] and for analysis of RBC deformations [39,58] to investigate, for the first time, the deformability and morphology changes of RBCs subjected to storage lesion
The correlations of storage time-dependent evolution of cell morphology index, shear modulus and bending modulus of the membrane, and cell surface area and volume were determined based on analogous experimental observations

Summary

Introduction

A red blood cell (RBC) transfusion is a critical and lifesaving medical procedure for anaemia caused by disease leading to inadequate bone marrow production or increased RBC breakdown, or by blood loss due to trauma or surgery [1,2,3,4]. RBCs undergo several biochemical, structural and functional changes, usually known as storage lesion [2,4,5,12,13,14,15,16,17,18,19,20] These changes include slowed metabolism with a decrease of adenosine triphosphate (ATP) concentration, oxidative damage with structural changes to band 3 protein and lipid peroxidation, functional loss of cation pumps and consequent loss of intracellular potassium and accumulation of sodium, and apoptotic changes of membrane phospholipids and membrane vesiculation [3,19,21,22,23]. Protein and lipid modifications, morphology changes, and membrane vesiculation are not reversible under in vivo conditions [15,22]

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