Rheological consequences of sickle-cell dehydration

Article type: Review Article

Authors: Stuart, John

Affiliations: Department of Haematology, Medical School, The University of Birmingham, Birmingham B15 2TT, UK

Abstract: Sickle-cell anaemia is the classical example of a rheological disorder, the poorly deformable sickle cell being responsible for impaired blood flow in the microcirculation causing intermittent tissue ischaemia. Loss of cation and water is a striking feature of the sickle cell, the consequential increase in concentration and polymerization of sickle haemoglobin causing an increase in cytoplasmic viscosity as quantified by impaired cell filterability through pores of 5μm diameter. Filtration methodology has been of particular value for studying the pathogenesis of cellular dehydration, for monitoring rheological changes during vaso-occlusive crisis, and for studying the action of drugs that inhibit cation flux across the cell membrane and thus preserve cell water. Such membrane active drugs include Ca2+-channel blockers (nitrendipine and nifedipine), Gardos channel inhibitors (cetiedil citrate, bepridil and nitrendipine), KCl cotransporter inhibitors, and drugs with a less specific or uncertain action (ticlopidine, oxpentifylline and piracetam). Serial ex vivo rheological studies during clinical trials of anti-sickling drugs offer an attractive method of monitoring efficacy. Such rheological measurements can be used instead of clinical end-points in pilot studies or to complement clinical end-points in multi-centre therapeutic trials. The application of rheological methods has substantially improved understanding of the pathogenes is of sickling and now provides a scientific basis for the evaluation of anti-sickling drugs.

Keywords: Rheology, erythrocyte deformability, sickle-cell anaemia,

DOI: 10.3233/CH-1992-12205

Journal: Clinical Hemorheology and Microcirculation, vol. 12, no. 2, pp. 203-216, 1992