Smith, RA;
Mankelow, TJ;
Drizou, D;
Bullock, T;
Latham, T;
Trompeter, S;
Blair, A;
(2021)
Large red cell-derived membrane particles are major contributors to hypercoagulability in sickle cell disease.
Scientific Reports
, 11
, Article 11035. 10.1038/s41598-021-90477-z.
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Abstract
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.
Type: | Article |
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Title: | Large red cell-derived membrane particles are major contributors to hypercoagulability in sickle cell disease |
Location: | England |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.1038/s41598-021-90477-z |
Publisher version: | http://dx.doi.org/10.1038/s41598-021-90477-z |
Language: | English |
Additional information: | This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
Keywords: | Anemia, Sickle Cell, Blood Coagulation, Erythrocyte Membrane, Phosphatidylserines, Thrombin, Thrombophilia |
UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics |
URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10184641 |
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