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A Feasibility Study Examining the Potential for a Predictive Test for Vaso-Occlusive Crises in Sickle Cell Disease Patients

Bullock, T. E. (2020) A Feasibility Study Examining the Potential for a Predictive Test for Vaso-Occlusive Crises in Sickle Cell Disease Patients. Doctoral thesis (Other), Manchester Metropolitan University, DClinSci.

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Abstract

Background There are 15,000 adults and children with Sickle Cell Disease (SCD) in England. Patients with homozygous (HbSS) SCD are at risk of painful Vaso-Occlusive Crises (VOCs), and haemolysis, caused by deoxygenated, sickle shaped erythrocytes occluding the microcirculation. VOCs may be exacerbated by the release of procoagulant Red Cell Derived Particles (RCDP), including autophagic vesicles (AV) into the bloodstream. RCDP release occurs during erythrocyte maturation and as part of sickling and unsickling of the erythrocyte upon repeated deoxygenation and reoxygenation. Aims The primary aim is to determine if AV numbers are elevated in SCD patients who are in SCD crisis when compared with steady state and healthy controls. Secondary aims include; whether levels of microvesicles correlate with VOC; whether levels of microvesicles correlate with length of admission and whether levels of microvesicles correlate with numbers of circulating reticulocytes in SCD patients admitted in VOC. Methods Samples from 11 SCD patients, admitted to University College London Hospital (UCLH) in VOC were analysed using confocal microscopy and flow cytometry techniques during admission, to quantify RCDP and AV on the RBC and in their plasma, respectively. Results were compared to healthy control samples and patients in a steady state of SCD. Results In confocal microscopy studies, statistically significant (p<0.0001) numbers of PS-positive RCDP, and GPA-pos RCDP were identified which is concordant with previous studies. In flow cytometry studies, a heterogeneous population of RCDP was present in the plasma of both healthy controls and SCD patients in steady state and in VOC. RCDP of an inside out orientation, most likely AVs, were present in the plasma of SCD patients in both steady state and VOC but were not significantly increased in either cohort. This is a novel finding. No population of MV was found to be a statistically significant predictor of VOC, which was limited by the experimental methodology. Conclusion The study of MV in SCD provides research opportunities into the prevention of SCD symptoms. Future studies should utilise imaging flow cytometry, to examine potentiators of the symptoms of SCD. They must be used to build a complete picture of the complex interactions in SCD patients; addressing the current slow progress in treatment and monitoring.

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