{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:11:48Z","timestamp":1792120308682,"version":"4.4.0"},"reference-count":36,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,3,8]],"date-time":"2019-03-08T00:00:00Z","timestamp":1552003200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013297","name":"Eurostars","doi-asserted-by":"publisher","award":["estar18105"],"award-info":[{"award-number":["estar18105"]}],"id":[{"id":"10.13039\/100013297","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["MD009124"],"award-info":[{"award-number":["MD009124"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In sickle cell disease (SCD), sickle hemoglobin (HbS) polymerizes upon deoxygenation, resulting in sickling of red blood cells (RBCs). These sickled RBCs have strongly reduced deformability, leading to vaso\u2010occlusive crises and chronic hemolytic anemia. To date, there are no reliable laboratory parameters or assays capable of predicting disease severity or monitoring treatment effects. We here report on the oxygenscan, a newly developed method to measure RBC deformability (expressed as Elongation Index \u2010 EI) as a function of pO<jats:sub>2<\/jats:sub>. Upon a standardized, 22\u2009minute, automated cycle of deoxygenation (pO<jats:sub>2<\/jats:sub> median 16\u2009mmHg\u2009\u00b1 0.17) and reoxygenation, a number of clinically relevant parameters are produced in a highly reproducible manner (coefficients of variation &lt;5%). In particular, physiological modulators of oxygen affinity, such as, pH and 2,3\u2010diphosphoglycerate showed a significant correlation (respectively R\u2009=\u2009\u20110.993 and R\u2009= 0.980) with Point of Sickling (PoS<jats:sub>5%<\/jats:sub>), which is defined as the pO<jats:sub>2<\/jats:sub> where a 5% decrease in EI is observed during deoxygenation. Furthermore, in vitro treatment with antisickling agents, including GBT440, which alter the oxygen affinity of hemoglobin, caused a reproducible left\u2010shift of the PoS, indicating improved deformability at lower oxygen tensions. When RBCs from 21 SCD patients were analyzed, we observed a significantly higher PoS in untreated homozygous SCD patients compared to treated patients and other genotypes. We conclude that the oxygenscan is a state\u2010of\u2010the\u2010art technique that allows for rapid analysis of sickling behavior in SCD patients. The method is promising for personalized treatment, development of new treatment strategies and could have potential in prediction of complications.<\/jats:p>","DOI":"10.1002\/ajh.25443","type":"journal-article","created":{"date-parts":[[2019,2,20]],"date-time":"2019-02-20T05:37:15Z","timestamp":1550641035000},"page":"575-584","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":73,"title":["Rapid and reproducible characterization of sickling during automated deoxygenation in sickle cell disease patients"],"prefix":"10.1002","volume":"94","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8306-8726","authenticated-orcid":false,"given":"Minke A.E.","family":"Rab","sequence":"first","affiliation":[{"name":"Laboratory of Clinical Chemistry &amp; Hematology University Medical Center Utrecht, Utrecht University  Utrecht The Netherlands"},{"name":"Van Creveldkliniek University Medical Center Utrecht, Utrecht University  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte A.","family":"van Oirschot","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Chemistry &amp; Hematology University Medical Center Utrecht, Utrecht University  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Bos","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Chemistry &amp; Hematology University Medical Center Utrecht, Utrecht University  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tesy H.","family":"Merkx","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Chemistry &amp; Hematology University Medical Center Utrecht, Utrecht University  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annet C.W.","family":"van Wesel","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Chemistry &amp; Hematology University Medical Center Utrecht, Utrecht University  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osheiza","family":"Abdulmalik","sequence":"additional","affiliation":[{"name":"Division of Hematology The Children's Hospital of Philadelphia  Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin K.","family":"Safo","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Institute for Structural Biology, Drug Discovery and Development, School of Pharmacy Virginia Commonwealth University  Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgitta A.","family":"Versluijs","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology University Medical Center Utrecht, Utrecht University  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maite E.","family":"Houwing","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology Erasmus University Medical Center\u2013 Sophia Children's Hospital  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjon H.","family":"Cnossen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology Erasmus University Medical Center\u2013 Sophia Children's Hospital  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jurgen","family":"Riedl","sequence":"additional","affiliation":[{"name":"Result Laboratory Albert Schweitzer Hospital  Dordrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger E.G.","family":"Schutgens","sequence":"additional","affiliation":[{"name":"Van Creveldkliniek University Medical Center Utrecht, Utrecht University  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard","family":"Pasterkamp","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Chemistry &amp; 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