{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T10:51:32Z","timestamp":1791283892152,"version":"4.1.0"},"reference-count":55,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,11,23]],"date-time":"2015-11-23T00:00:00Z","timestamp":1448236800000},"content-version":"vor","delay-in-days":326,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2015,1,1]],"date-time":"2015-01-01T00:00:00Z","timestamp":1420070400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["www.tandfonline.com"],"crossmark-restriction":true},"short-container-title":["J of Extracellular Vesicle"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Circulating microparticles (MP) have been described in sickle cell anaemia (SCA); however, their interaction with endothelial markers remains unclear. We investigated the relationship between MP, protein C (PC), free protein S (PS), nitric oxide (NO), endothelin\u20101 (ET\u20101) and adrenomedullin (ADM) in a large cohort of paediatric patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>A total of 111 children of African ethnicity with SCA: 51\u00a0in steady state; 15\u00a0in crises; 30 on hydroxyurea (HU) therapy; 15 on transfusion; 17 controls (HbAA) of similar age\/ethnicity. MP were analysed by flow cytometry using: Annexin V (AV), CD61, CD42a, CD62P, CD235a, CD14, CD142 (tissue factor), CD201 (endothelial PC receptor), CD62E, CD36 (TSP\u20101), CD47 (TSP\u20101 receptor), CD31 (PECAM), CD144 (VE\u2010cadherin). Protein C, free PS, NO, pro\u2010ADM and C\u2010terminal ET\u20101 were also measured.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Total MP AV was lower in crisis (1.26\u00d710<jats:sup>6<\/jats:sup> ml<jats:sup>\u22121<\/jats:sup>; 0.56\u20132.44\u00d710<jats:sup>6<\/jats:sup>) and steady state (1.35\u00d710<jats:sup>6<\/jats:sup> ml<jats:sup>\u22121<\/jats:sup>; 0.71\u20133.0\u00d710<jats:sup>6<\/jats:sup>) compared to transfusion (4.33\u00d710<jats:sup>6<\/jats:sup> ml<jats:sup>\u22121<\/jats:sup>; 1.6\u20139.2\u00d710<jats:sup>6<\/jats:sup>, p&lt;0.01). Protein C levels were significantly lower in crisis (median 0.52 IU ml<jats:sup>\u22121<\/jats:sup>; interquartile range 0.43\u20130.62) compared with all other groups: HbAA (0.72 IU ml<jats:sup>\u22121<\/jats:sup>; 0.66\u20130.82, p&lt;0.001); HU (0.67 IU ml<jats:sup>\u22121<\/jats:sup>; 0.58\u20130.77, p&lt;0.001); steady state (0.63 IU ml<jats:sup>\u22121<\/jats:sup>; 0.54\u20130.70, p&lt;0.05) and transfusion (0.60 IU ml<jats:sup>\u22121<\/jats:sup>; 0.54\u20130.70, p&lt;0.05). In addition, levels were significantly reduced in steady state (0.63 IU ml<jats:sup>\u22121<\/jats:sup>; 0.54\u20130.70) compared with HbAA (0.72 IU ml<jats:sup>\u22121<\/jats:sup>; 0.66\u20130.80, p&lt;0.01). PS levels were significantly higher in HbAA (0.85 IU ml<jats:sup>\u22121<\/jats:sup>; 0.72\u20130.97) compared with crisis (0.49 IU ml<jats:sup>\u22121<\/jats:sup>; 0.42\u20130.64, p&lt;0.001), HU (0.65 IU ml<jats:sup>\u22121<\/jats:sup>; 0.56\u20130.74, p&lt;0.01) and transfusion (0.59 IU ml<jats:sup>\u22121<\/jats:sup>; 0.47\u20130.71, p&lt;0.01). There was also a significant difference in crisis patients compared with steady state (0.49 IU ml<jats:sup>\u22121<\/jats:sup>; 0.42\u20130.64 vs. 0.68 IU ml<jats:sup>\u22121<\/jats:sup>; 0.58\u20130.79, p&lt;0.05). There was high correlation (R&gt;0.9, p&lt;0.05) between total numbers of AV\u2010positive MP (MP AV) and platelet MP expressing non\u2010activation platelet markers. There was a lower correlation between MP AV and MP CD62P (R=0.73, p&lt;0.05) (platelet activation marker), and also a lower correlation between percentage of MP expressing CD201 (%MP CD201) and %MP CD14 (R=0.627, p&lt;0.001). %MP CD201 was higher in crisis (11.6%) compared with HbAA (3.2%, p&lt;0.05); %MP CD144 was higher in crisis (7.6%) compared with transfusion (2.1%, p&lt;0.05); %CD14 (0.77%) was higher in crisis compared with transfusion (0.0%, p&lt;0.05) and steady state (0.0%, p&lt;0.01); MP CD14 was detectable in a higher number of samples (92%) in crisis compared with the rest (40%); %MP CD235a was higher in crisis (17.9%) compared with transfusion (8.9%), HU (8.7%) and steady state (9.9%, p&lt;0.05); %CD62E did not differ significantly across the groups and CD142 was undetectable. Pro\u2010ADM levels were raised in chest crisis: 0.38\u00a0nmol L<jats:sup>\u22121<\/jats:sup> (0.31\u20130.49) versus steady state: 0.27\u00a0nmol L<jats:sup>\u22121<\/jats:sup> (0.25\u20130.32; p&lt;0.01) and control: 0.28\u00a0nmol L<jats:sup>\u22121<\/jats:sup> (0.27\u20130.31; p&lt;0.01). CT\u2010proET\u20101 levels were reduced in patients on HU therapy: 43.6 pmol L<jats:sup>\u22121<\/jats:sup> (12.6\u201349.6) versus control: 55.1 pmol L<jats:sup>\u22121<\/jats:sup> (45.2\u201363.9; p&lt;0.05). NO levels were significantly lower in chest crisis (19.3\u00a0mmol L<jats:sup>\u22121<\/jats:sup> plasma; 10.7\u201319.9) compared with HU (22.2\u00a0mmol L<jats:sup>\u22121<\/jats:sup> plasma; 18.3\u201328.4; p&lt;0.05), and HbSC (30.6\u00a0mmol L<jats:sup>\u22121<\/jats:sup> plasma; 20.8\u201339.5; p&lt;0.05) and approach significance when compared with steady state (22.5mmol L<jats:sup>\u22121<\/jats:sup> plasma; 16.9\u201328.2; p=0.07).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Protein C and free PS are reduced in crisis with lower numbers of platelet MP and higher percentage of markers of endothelial damage and of red cell origin. During chest crisis, ADM and ET\u20101 were elevated suggesting a role for therapy inhibiting ET\u20101\u00a0in chest crisis.<\/jats:p><\/jats:sec>","DOI":"10.3402\/jev.v4.28414","type":"journal-article","created":{"date-parts":[[2015,11,23]],"date-time":"2015-11-23T08:09:24Z","timestamp":1448266164000},"update-policy":"https:\/\/doi.org\/10.1080\/tandf_crossmark_01","source":"Crossref","is-referenced-by-count":57,"title":["Circulating microparticles, protein C, free protein S and endothelial vascular markers in children with sickle cell anaemia"],"prefix":"10.1002","volume":"4","author":[{"given":"Andrea","family":"Piccin","sequence":"first","affiliation":[{"name":"Irish Blood Transfusion Service Dublin Ireland"},{"name":"Our Lady's Children Hospital Dublin Ireland"},{"name":"Department of Haematology Trinity College Dublin Dublin Ireland"},{"name":"Haematology Department San Maurizio Regional Hospital Bolzano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciaran","family":"Murphy","sequence":"additional","affiliation":[{"name":"Irish Blood Transfusion Service Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elva","family":"Eakins","sequence":"additional","affiliation":[{"name":"Irish Blood Transfusion Service Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Kunde","sequence":"additional","affiliation":[{"name":"B.R.A.H.M.S. 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