Large red cell-derived membrane particles are major contributors to hypercoagulability in sickle cell disease.

Autor:	Smith RA; Bristol Institute for Transfusion Sciences, National Health Service Blood and Transplant, Northway, Filton, Bristol, BS34 7QH, UK.; NIHR Blood and Transplant Research Unit, University of Bristol, Bristol, UK.; School of Biochemistry, University of Bristol, Bristol, UK., Mankelow TJ; Bristol Institute for Transfusion Sciences, National Health Service Blood and Transplant, Northway, Filton, Bristol, BS34 7QH, UK. tosti.mankelow@nhsbt.nhs.uk.; NIHR Blood and Transplant Research Unit, University of Bristol, Bristol, UK. tosti.mankelow@nhsbt.nhs.uk., Drizou D; Bristol Institute for Transfusion Sciences, National Health Service Blood and Transplant, Northway, Filton, Bristol, BS34 7QH, UK.; NIHR Blood and Transplant Research Unit, University of Bristol, Bristol, UK.; School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK., Bullock T; Bristol Institute for Transfusion Sciences, National Health Service Blood and Transplant, Northway, Filton, Bristol, BS34 7QH, UK., Latham T; Bristol Institute for Transfusion Sciences, National Health Service Blood and Transplant, Northway, Filton, Bristol, BS34 7QH, UK., Trompeter S; Joint Red Cell Unit, Haematology Department, University College London National Health Service Foundation Trust, London, UK., Blair A; Bristol Institute for Transfusion Sciences, National Health Service Blood and Transplant, Northway, Filton, Bristol, BS34 7QH, UK.; NIHR Blood and Transplant Research Unit, University of Bristol, Bristol, UK.; School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK., Anstee DJ; Bristol Institute for Transfusion Sciences, National Health Service Blood and Transplant, Northway, Filton, Bristol, BS34 7QH, UK.; NIHR Blood and Transplant Research Unit, University of Bristol, Bristol, UK.
Jazyk:	angličtina
Zdroj:	Scientific reports [Sci Rep] 2021 May 26; Vol. 11 (1), pp. 11035. Date of Electronic Publication: 2021 May 26.
DOI:	10.1038/s41598-021-90477-z
Abstrakt:	Sickle cell disease (SCD) is one of the most common inherited single gene disorders. Polymerisation of sickle hemoglobin results in erythrocytes that are inflexible and adherent, leading to coagulation, vascular and cellular activation and resultant blood vessel blockage. Previous studies have observed elevated numbers of red cell-derived particles (RCDP), also denoted extracellular vesicles, in SCD plasma. Here, imaging flow cytometry was used to quantify all RCDP in SCD plasma. A more heterogenous population of RCDP was observed than previously reported. Significantly, large right side-out red cell macrovesicles (MaV), 7 µm in diameter, were identified. Most RCDP were right side-out but a minor population of inside-out vesicles was also present. Electron micrographs confirmed the heterogenous nature of the RCDP detected. All MaV are decorated with prothrombotic phosphatidylserine (PS) and their removal from plasma lengthened clotting times by more than three-fold. Removal of all right side-out RCDP from SCD patient plasma samples resulted in a seven-fold increase in clotting time. These results indicate that MaV comprise a large area of prothrombotic membrane and are thus major contributors to hypercoagulation in SCD. Consequently, controlled removal of MaV and PS exposed RCDP from plasma could provide a novel therapy for managing this disease.
Databáze:	MEDLINE
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