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However, ischemic end\u2010organ injury remains common suggesting that tissue oxygen delivery may be impaired by microvascular dysregulation or damage. To test this hypothesis, we performed fingertip laser Doppler flowmetry measurements at the base of the nailbed and regional oxygen saturation (rSO<jats:sub>2<\/jats:sub>) on the dorsal surface of the same hand. This was done during flow mediated dilation (FMD) studies in 26 chronically transfused SCD, 75 non\u2010transfused SCD, and 18 control subjects. Chronically transfused SCD patients were studied prior to and following a single transfusion and there was no acute change in rSO<jats:sub>2<\/jats:sub> or perfusion. Laser Doppler estimates of resting perfusion were 76% higher in non\u2010transfused and 110% higher in transfused SCD patients, compared to control subjects. In contrast, rSO<jats:sub>2<\/jats:sub> was 12 saturation points lower in non\u2010transfused SCD patients, but normal in the transfused SCD patients. During cuff occlusion, rSO<jats:sub>2<\/jats:sub> declined at the same rate in all subjects suggesting similar intrinsic oxygen consumption rates. Upon cuff release, laser doppler post occlusive hyperemia was blunted in SCD patients in proportion to their resting perfusion values. Transfusion therapy did not improve the hyperemia response. FMD was impaired in SCD subjects but partially ameliorated in transfused SCD subjects. Taken together, non\u2010transfused SCD subjects demonstrate impaired conduit artery FMD, impaired microcirculatory post\u2010occlusive hyperemia, and resting hypoxia in the hand despite compensated oxygen delivery, suggesting impaired oxygen supply\u2010demand matching. Transfusion improves FMD and oxygen supply\u2010demand matching but not microcirculation hyperemic response.<\/jats:p>","DOI":"10.1002\/ajh.25476","type":"journal-article","created":{"date-parts":[[2019,3,28]],"date-time":"2019-03-28T00:17:51Z","timestamp":1553732271000},"page":"678-688","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Sickle cell microvascular paradox\u2014oxygen supply\u2010demand mismatch"],"prefix":"10.1002","volume":"94","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2086-9569","authenticated-orcid":false,"given":"Jon A.","family":"Detterich","sequence":"first","affiliation":[{"name":"Division of Cardiology, Children's Hospital Los Angeles University of Southern California Keck School of Medicine  Los Angeles California"},{"name":"Department of Physiology and Neuroscience University of Southern California Keck School of Medicine  Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Kato","sequence":"additional","affiliation":[{"name":"Division of Pediatric Pulmonology Children's Hospital Los Angeles  Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Bush","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Southern California Viterbi School of Engineering"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9023-7903","authenticated-orcid":false,"given":"Patjanaporn","family":"Chalacheva","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Southern California Viterbi School of Engineering"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek","family":"Ponce","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Children's Hospital Los Angeles University of Southern California Keck School of Medicine  Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madushka","family":"De Zoysa","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Children's Hospital Los Angeles University of Southern California Keck School of Medicine  Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Payal","family":"Shah","sequence":"additional","affiliation":[{"name":"Division of Hematology Oncology, Children's Hospital Los Angeles University of Southern California Keck School of Medicine  Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C.","family":"Khoo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Southern California Viterbi School of Engineering"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herbert J.","family":"Meiselman","sequence":"additional","affiliation":[{"name":"Department of Physiology and Neuroscience University of Southern California Keck School of Medicine  Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9878-6029","authenticated-orcid":false,"given":"Thomas D.","family":"Coates","sequence":"additional","affiliation":[{"name":"Division of Hematology Oncology, Children's Hospital Los Angeles University of Southern California Keck School of Medicine  Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Wood","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Children's Hospital Los Angeles University of Southern California Keck School of Medicine  Los Angeles California"},{"name":"Department of Biomedical Engineering University of Southern California Viterbi School of Engineering"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,4,19]]},"reference":[{"issue":"1","key":"e_1_2_9_2_1","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1182\/blood.V4.1.66.66","article-title":"A rapid diagnostic test for sickle cell anemia","volume":"4","author":"Itano HA","year":"1949","journal-title":"Blood"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.110.2865.543"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI106273"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199406093302303"},{"key":"e_1_2_9_6_1","unstructured":"SteinerCA MillerJL.Sickle cell disease patients in U.S. Hospitals 2004: Statistical Brief #21. 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