{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:18:21Z","timestamp":1784074701253,"version":"3.55.0"},"reference-count":63,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2021,1,7]],"date-time":"2021-01-07T00:00:00Z","timestamp":1609977600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Clinical Hemorheology and Microcirculation"],"published-print":{"date-parts":[[2022,2,17]]},"abstract":"<jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Red blood cell (RBC)-modifying therapies have provided new opportunities for patients with sickle cell disease, although the absence of validated biomarkers of RBC function is a barrier to FDA approval and clinical adoption. Flow Adhesion (FA) and Mechanical Fragility (MF) biomarkers objectively stratify individuals with SCD into pro-adhesive vs pro-hemolytic phenotypes respectively, which may potentially help predict therapeutic responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>OBJECTIVE:<\/jats:title>\n                    <jats:p>A Phase 3 clinical trial to determine the effectiveness of vepoloxamer, an RBC-modifying therapy in sickle cell disease (SCD), failed to meet its primary clinical outcome. The aim of this study was to determine whether standardized flow adhesion and mechanical fragility bioassays could differentiate cellular level \u201cresponders\u201d from \u201cnon-responders\u201d to vepoloxamer treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      Standardized biomarkers of RBC function (adhesion and mechanical fragility) were utilized in this study to assess the effect of veploxamer on blood samples collected from SCD subjects and to determine whether our assays could differentiate cellular-level \u201cresponders\u201d from \u201cnon-responders\u201d to vepoloxamer treatment. A Wilcoxon signed-rank test was used to test for differences in adhesion in response to varying vepoloxamer treatments and a Wilcoxon Mann-Whitney test was used to assess differences in mechanical fragility, pre- and post-vepoloxamer treatment. A\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      -value&lt;0.05 was considered significant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      In this study, we report that\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      treatment with vepoloxamer reduced adhesion by &gt;75%in 54%of patient samples and induced changes in the membranes of sickle erythrocytes (SSRBCs) making sickle cells behave more like normal erythrocytes (AARBCs) in terms of their resistance to hemolysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>CONCLUSION:<\/jats:title>\n                    <jats:p>This study demonstrates that the standardized flow adhesion and mechanical fragility biomarkers described here may be useful tools to predict clinical responders to RBC-modifying therapies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/ch-200944","type":"journal-article","created":{"date-parts":[[2021,1,12]],"date-time":"2021-01-12T17:38:24Z","timestamp":1610473104000},"page":"127-138","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Can red blood cell function assays assess response to red cell-modifying therapies?"],"prefix":"10.1177","volume":"80","author":[{"given":"Jennell","family":"White","sequence":"first","affiliation":[{"name":"Wayne State University","place":["USA"]},{"name":"Functional Fluidics, Detroit, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moira","family":"Lancelot","sequence":"additional","affiliation":[{"name":"Emory University","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiufeng","family":"Gao","sequence":"additional","affiliation":[{"name":"Functional Fluidics, Detroit, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Tarasev","sequence":"additional","affiliation":[{"name":"Functional Fluidics, Detroit, MI, USA"},{"name":"Blaze Medical Devices, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumita","family":"Chakraborty","sequence":"additional","affiliation":[{"name":"Blaze Medical Devices, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marty","family":"Emanuele","sequence":"additional","affiliation":[{"name":"Mast therapeutics, Inc., San Diego, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick C.","family":"Hines","sequence":"additional","affiliation":[{"name":"Functional Fluidics, Detroit, MI, USA"},{"name":"Critical Care Medicine, Children\u2019s Hospital of Michigan, Detroit, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2021,1,7]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198005013021803"},{"key":"e_1_3_4_3_2","first-page":"94","article-title":"Erytrocyte adherence to endothelium as a determinant of vasocclusive severity in sickle cell disease","volume":"93","author":"Hebbel RP","year":"1980","unstructured":"HebbelRP, BoogaertsMA, KoresawaS, JacobHS, EatonJW, SteinbergMH. 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