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We have shown that mental stress, pain and cold, and events reported by patients to trigger SCD vaso\u2010occlusive crisis (VOC), cause rapid and significant decrease in blood flow, reducing the likelihood that RBC could transit the microvasculature before sickling occurs. However, the critical link between decrease in microvascular blood flow and the incidence of future sickle VOC has never been established experimentally in humans. Using data from centrally adjudicated, overnight polysomnograms (PSG), previously collected in a prospective multi\u2010center cohort sleep study, we analyzed the beat\u2010to\u2010beat amplitudes of vasoconstriction reported by the fingertip photoplethysmogram in 212 children and adolescents with SCD and developed an algorithm that detects vasoconstriction events and quantifies the magnitude (M<jats:sub>vasoc<\/jats:sub>), duration, and frequency of vasoconstriction that reflect the individual's inherent peripheral vasoreactivity. The propensity to vasoconstrict, quantified by median M<jats:sub>vasoc<\/jats:sub>, predicted the incidence rate of post\u2010PSG severe acute vaso\u2010occlusive pain events (<jats:italic>P<\/jats:italic> = .006) after accounting for age and hemoglobin. Indices of sleep\u2010disordered breathing contributed to median M<jats:sub>vasoc<\/jats:sub> but did not predict future pain rate. Median M<jats:sub>vasoc<\/jats:sub> was not associated with vaso\u2010occlusive pain events that occurred prior to each PSG. These results show that SCD individuals with high inherent propensity to vasoconstrict have more frequent severe acute pain events. Our empirical findings are consistent with the fundamental SCD hypothesis that decreased microvascular flow promotes microvascular occlusion.<\/jats:p>","DOI":"10.1002\/ajh.26014","type":"journal-article","created":{"date-parts":[[2020,10,7]],"date-time":"2020-10-07T18:45:43Z","timestamp":1602096343000},"page":"60-68","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Nocturnal peripheral vasoconstriction predicts the frequency of severe acute pain episodes in children with sickle cell disease"],"prefix":"10.1002","volume":"96","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9023-7903","authenticated-orcid":false,"given":"Patjanaporn","family":"Chalacheva","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering Carnegie Mellon University  Pittsburgh Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunhua","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Southern California  Los Angeles California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carol L.","family":"Rosen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Pulmonary Allergy\/Immunology and Sleep, University Hospitals\u2010Cleveland Medical Center, Rainbow Babies and Children's Hospitals  Cleveland Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0574-1604","authenticated-orcid":false,"given":"Michael R.","family":"DeBaun","sequence":"additional","affiliation":[{"name":"Division of Hematology\u2010Oncology, Department of Pediatrics Vanderbilt University School of Medicine  Nashville Tennessee"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael C. K.","family":"Khoo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Southern California  Los Angeles California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9878-6029","authenticated-orcid":false,"given":"Thomas D.","family":"Coates","sequence":"additional","affiliation":[{"name":"Cancer and Blood Disease Institute, Children's Hospital Los Angeles, Department of Pediatrics University of Southern California Keck School of Medicine  Los Angeles California"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,10,23]]},"reference":[{"issue":"2835","key":"e_1_2_9_2_1","first-page":"443","article-title":"Sickle cell anemia, a molecular disease","volume":"109","author":"Pauling L","year":"1949","journal-title":"Science"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.71.12.4864"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3233\/CH-189011"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.24858"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2018.211391"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm8101690"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201103-0537OC"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.12463"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCP.0b013e3283318585"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/19.suppl_10.S193"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1996.80.5.1627"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1109\/TBME.2005.859789"},{"issue":"7","key":"e_1_2_9_14_1","first-page":"899","article-title":"Periodic limb movements and disrupted sleep in children with sickle cell disease","volume":"34","author":"Rogers VE","year":"2011","journal-title":"Sleep"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11325-017-1476-7"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25048"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25013"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1088\/0967-3334\/28\/3\/R01"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.2174\/157340312801215782"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00111.2019"},{"issue":"3","key":"e_1_2_9_21_1","first-page":"354","article-title":"Standards of measurement, physiological interpretation, and clinical use. 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