{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T21:19:27Z","timestamp":1777497567119,"version":"3.51.4"},"reference-count":58,"publisher":"SAGE Publications","issue":"2-3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CH"],"published-print":{"date-parts":[[2018,3,28]]},"DOI":"10.3233\/ch-189011","type":"journal-article","created":{"date-parts":[[2018,3,30]],"date-time":"2018-03-30T10:17:02Z","timestamp":1522405022000},"page":"251-262","source":"Crossref","is-referenced-by-count":28,"title":["Autonomic nervous system involvement in sickle cell disease"],"prefix":"10.1177","volume":"68","author":[{"given":"Thomas D.","family":"Coates","sequence":"first","affiliation":[{"name":"Section of Hematology, Children\u2019s Center for Cancer and Blood Diseases, Children\u2019s Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patjanaporn","family":"Chalacheva","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lonnie","family":"Zeltzer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Pediatric Pain and Palliative Care Program Division of Hematology-Oncology, Department of Pediatrics, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael C.K.","family":"Khoo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","reference":[{"key":"10.3233\/CH-189011_ref1","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1111\/j.1537-2995.2006.00823.x","article-title":"Rheologic behavior of sickle and normal red blood cell mixtures in sickle plasma: Implications for transfusion therapy","volume":"46","author":"Alexy","year":"2006","journal-title":"Transfusion"},{"key":"10.3233\/CH-189011_ref2","doi-asserted-by":"crossref","first-page":"155","DOI":"10.3233\/CH-2010-1270","article-title":"Sickle cell disease: Selected aspects of pathophysiology","volume":"44","author":"Alexy","year":"2010","journal-title":"Clin Hemorheol Microcirc"},{"key":"10.3233\/CH-189011_ref3","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1056\/NEJMoa1611770","article-title":"Crizanlizumab for the prevention of pain crises in sickle cell disease","volume":"376","author":"Ataga","year":"2017","journal-title":"N Engl J Med"},{"key":"10.3233\/CH-189011_ref4","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/j.hoc.2005.07.008","article-title":"Pain management of sickle cell disease","volume":"19","author":"Ballas","year":"2005","journal-title":"Hematol Oncol Clin North Am"},{"key":"10.3233\/CH-189011_ref5","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.2147\/JPR.S131859","article-title":"The effect of hypnosis on pain and peripheral blood flow in sickle-cell disease: A pilot study","volume":"10","author":"Bhatt","year":"2017","journal-title":"J Pain Res"},{"key":"10.3233\/CH-189011_ref6","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/0165-1838(81)90003-5","article-title":"Cardiac rhythmicity of skin sympathetic activity recorded from peripheral nerves in man","volume":"4","author":"Bini","year":"1981","journal-title":"J Auton Nerv Syst"},{"key":"10.3233\/CH-189011_ref7","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1097\/j.pain.0000000000000104","article-title":"Sensitization of nociceptive spinal neurons contributes to pain in a transgenic model of sickle cell disease","volume":"156","author":"Cataldo","year":"2015","journal-title":"Pain"},{"key":"10.3233\/CH-189011_ref8","first-page":"3","article-title":"Autonomic responses to cold face stimulation in sickle cell disease: A time-varying model analysis","author":"Chalacheva","year":"2015","journal-title":"Physiol Rep"},{"key":"10.3233\/CH-189011_ref9","doi-asserted-by":"crossref","first-page":"e0178353","DOI":"10.1371\/journal.pone.0178353","article-title":"Biophysical markers of the peripheral vasoconstriction response to pain in sickle cell disease","volume":"12","author":"Chalacheva","year":"2017","journal-title":"PLoS One"},{"key":"10.3233\/CH-189011_ref10","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1111\/bjh.14064","article-title":"Changes in autonomic nervous activity during vaso-occlusive crisis in patients with sickle cell anaemia","volume":"177","author":"Charlot","year":"2017","journal-title":"Br J Haematol"},{"key":"10.3233\/CH-189011_ref11","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.nicl.2017.04.023","article-title":"Hemoglobin and mean platelet volume predicts diffuse T1-MRI white matter volume decrease in sickle cell disease patients","volume":"15","author":"Choi","year":"2017","journal-title":"Neuroimage Clin"},{"key":"10.3233\/CH-189011_ref12","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1529\/biophysj.104.051250","article-title":"Understanding the shape of sickled red cells","volume":"88","author":"Christoph","year":"2005","journal-title":"Biophys J"},{"key":"10.3233\/CH-189011_ref13","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1529\/biophysj.104.051250","article-title":"Understanding the shape of sickled red cells","volume":"88","author":"Christoph","year":"2005","journal-title":"Biophysical Journal"},{"key":"10.3233\/CH-189011_ref14","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1182\/blood-2010-11-314484","article-title":"So what if blood is thicker than water?","volume":"117","author":"Coates","year":"2011","journal-title":"Blood"},{"key":"10.3233\/CH-189011_ref15","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1164\/rccm.201105-0941ED","article-title":"Altered autonomic nervous system function in sickle cell disease","volume":"184","author":"Connes","year":"2011","journal-title":"Am J Respir Crit Care Med"},{"key":"10.3233\/CH-189011_ref16","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.blre.2015.08.005","article-title":"The role of blood rheology in sickle cell disease","volume":"30","author":"Connes","year":"2016","journal-title":"Blood Rev"},{"key":"10.3233\/CH-189011_ref17","doi-asserted-by":"crossref","first-page":"L1","DOI":"10.1088\/0967-3334\/29\/9\/L01","article-title":"Comment on \u2018Abnormal autonomic cardiac response to transient hypoxia in sickle cell anemia\u2019","volume":"29","author":"Connes","year":"2008","journal-title":"Physiol Meas"},{"key":"10.3233\/CH-189011_ref18","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.crvi.2012.09.003","article-title":"Autonomic nervous system dysfunction: Implication in sickle cell disease","volume":"336","author":"Connes","year":"2013","journal-title":"C R Biol"},{"key":"10.3233\/CH-189011_ref19","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1111\/j.1475-097X.2006.00655.x","article-title":"Nocturnal autonomic nervous system activity impairment in sickle cell trait carriers","volume":"26","author":"Connes","year":"2006","journal-title":"Clin Physiol Funct Imaging"},{"key":"10.3233\/CH-189011_ref20","doi-asserted-by":"crossref","first-page":"E212","DOI":"10.1002\/ajh.23819","article-title":"Factors predicting future ACS episodes in children with sickle cell anemia","volume":"89","author":"DeBaun","year":"2014","journal-title":"Am J Hematol"},{"key":"10.3233\/CH-189011_ref21","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1182\/blood-2014-12-614370","article-title":"Chronic transfusion therapy improves but does not normalize systemic and pulmonary vasculopathy in sickle cell disease","volume":"126","author":"Detterich","year":"2015","journal-title":"Blood"},{"key":"10.3233\/CH-189011_ref22","doi-asserted-by":"crossref","first-page":"2719","DOI":"10.1182\/blood-2017-02-765891","article-title":"Treating sickle cell disease by targeting HbS polymerization","volume":"129","author":"Eaton","year":"2017","journal-title":"Blood"},{"key":"10.3233\/CH-189011_ref23","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1182\/blood.V47.4.621.621","article-title":"Editorial: Delay time of gelation: A possible determinant of clinical severity in sickle cell disease","volume":"47","author":"Eaton","year":"1976","journal-title":"Blood"},{"key":"10.3233\/CH-189011_ref24","doi-asserted-by":"crossref","first-page":"3224","DOI":"10.1161\/01.CIR.96.9.3224","article-title":"Sympathovagal balance: A critical appraisal","volume":"96","author":"Eckberg","year":"1997","journal-title":"Circulation"},{"key":"10.3233\/CH-189011_ref25","first-page":"354","article-title":"Standards of measurement, physiological interpretation, and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology","volume":"17","author":"ESC\/NASPE Heart rate variability","year":"1996","journal-title":"Eur Heart J"},{"key":"10.3233\/CH-189011_ref26","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/0022-2836(85)90174-3","article-title":"Kinetics of sickle hemoglobin polymerization I. Studies using temperature-jump and laser photolysis techniques","volume":"183","author":"Ferrone","year":"1985","journal-title":"J Mol Biol"},{"key":"10.3233\/CH-189011_ref27","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/0022-2836(85)90175-5","article-title":"Kinetics of sickle hemoglobin polymerization. II. A double nucleation mechanism","volume":"183","author":"Ferrone","year":"1985","journal-title":"J Mol Biol"},{"key":"10.3233\/CH-189011_ref28","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1056\/NEJM198005013021803","article-title":"Erythrocyte adherence to endothelium in sickle-cell anemia. A possible determinant of disease severity","volume":"302","author":"Hebbel","year":"1980","journal-title":"N Engl J Med"},{"key":"10.3233\/CH-189011_ref29","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1172\/JCI109646","article-title":"Abnormal adherence of sickle erythrocytes to cultured vascular endothelium: Possible mechanism for microvascular occlusion in sickle cell disease","volume":"65","author":"Hebbel","year":"1980","journal-title":"J Clin Invest"},{"key":"10.3233\/CH-189011_ref30","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/0022-2836(86)90324-4","article-title":"Kinetics of sickle hemoglobin polymerization III. Nucleation rates determined from stochastic fluctuations in polymerization progress curves","volume":"189","author":"Hofrichter","year":"1986","journal-title":"J Mol Biol"},{"key":"10.3233\/CH-189011_ref31","doi-asserted-by":"crossref","unstructured":"Hofrichter J , Ross PD , Eaton WA . Kinetics and mechanism of deoxyhemoglobin S gelation: A new approach to understanding sickle cell disease. Proceedings of the National Academy of Sciences of the United States of America. 1974;71:4864\u20138.","DOI":"10.1073\/pnas.71.12.4864"},{"key":"10.3233\/CH-189011_ref32","doi-asserted-by":"crossref","first-page":"4864","DOI":"10.1073\/pnas.71.12.4864","article-title":"Kinetics and mechanism of deoxyhemoglobin S gelation: A new approach to understanding sickle cell disease","volume":"71","author":"Hofrichter","year":"1974","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.3233\/CH-189011_ref33","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","year":"1949","journal-title":"Blood"},{"key":"10.3233\/CH-189011_ref34","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.blre.2006.07.001","article-title":"Deconstructing sickle cell disease: Reappraisal of the role of hemolysis in the development of clinical subphenotypes","volume":"21","author":"Kato","year":"2007","journal-title":"Blood Rev"},{"key":"10.3233\/CH-189011_ref35","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1172\/JCI89741","article-title":"Intravascular hemolysis and the pathophysiology of sickle cell disease","volume":"127","author":"Kato","year":"2017","journal-title":"J Clin Invest"},{"key":"10.3233\/CH-189011_ref36","doi-asserted-by":"crossref","unstructured":"Khaleel M , Puliyel M , Shah P , Sunwoo J , Kato RM , Chalacheva P , Thuptimdang W , Detterich J , Wood JC , Tsao J , Zeltzer L , Sposto R , Khoo MCK , Coates TD . Individuals with sickle cell disease have a significantly greater vasoconstriction response to thermal pain than controls and have significant vasoconstriction in response to anticipation of pain. Am J Hematol. 2017.","DOI":"10.1002\/ajh.24858"},{"key":"10.3233\/CH-189011_ref37","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1007\/s10558-007-9041-9","article-title":"Modeling of autonomic control in sleep-disordered breathing","volume":"8","author":"Khoo","year":"2008","journal-title":"Cardiovasc Eng"},{"key":"10.3233\/CH-189011_ref38","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1016\/S0140-6736(00)04821-2","article-title":"Nocturnal hypoxaemia and central-nervous-system events in sickle-cell disease","volume":"357","author":"Kirkham","year":"2001","journal-title":"Lancet"},{"key":"10.3233\/CH-189011_ref39","doi-asserted-by":"crossref","first-page":"H381","DOI":"10.1152\/ajpheart.00077.2015","article-title":"Neural control of circulation and exercise: A translational approach disclosing interactions between central command, arterial baroreflex, and muscle metaboreflex","volume":"309","author":"Michelini","year":"2015","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"10.3233\/CH-189011_ref40","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.3324\/haematol.2011.047365","article-title":"Frequency of pain crises in sickle cell anemia and its relationship with the sympatho-vagal balance, blood viscosity and inflammation","volume":"96","author":"Nebor","year":"2011","journal-title":"Haematologica"},{"key":"10.3233\/CH-189011_ref41","doi-asserted-by":"crossref","unstructured":"Niss O , Fleck R , Makue F , Alsaied T , Desai P , Towbin JA , Malik P , Taylor MD , Quinn CT . Association between diffuse myocardial fibrosis and diastolic dysfunction in sickle cell anemia. Blood. 2017.","DOI":"10.1182\/blood-2017-02-767624"},{"key":"10.3233\/CH-189011_ref42","doi-asserted-by":"crossref","first-page":"69","DOI":"10.4149\/endo_2010_02_69","article-title":"Multilevel interactions between the sympathetic and parasympathetic nervous systems: A minireview","volume":"44","author":"Ondicova","year":"2010","journal-title":"Endocr Regul"},{"key":"10.3233\/CH-189011_ref43","first-page":"443","article-title":"Sickle cell anemia, a molecular disease","volume":"109","author":"Pauling","year":"1949","journal-title":"Science"},{"key":"10.3233\/CH-189011_ref44","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1007\/s10286-005-0300-9","article-title":"Autonomic reactivity and clinical severity in children with sickle cell disease","volume":"15","author":"Pearson","year":"2005","journal-title":"Clin Auton Res"},{"key":"10.3233\/CH-189011_ref46","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1056\/NEJM199107043250103","article-title":"Pain in sickle cell disease. Rates and risk factors","volume":"325","author":"Platt","year":"1991","journal-title":"N Engl J Med"},{"key":"10.3233\/CH-189011_ref47","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.resp.2010.08.021","article-title":"Mechanisms of sympathetic activation and blood pressure elevation by intermittent hypoxia","volume":"174","author":"Prabhakar","year":"2010","journal-title":"Respir Physiol Neurobiol"},{"key":"10.3233\/CH-189011_ref48","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1111\/j.1365-2141.2007.06927.x","article-title":"Daytime steady-state haemoglobin desaturation is a risk factor for overt stroke in children with sickle cell anaemia","volume":"140","author":"Quinn","year":"2008","journal-title":"British Journal of Haematology"},{"key":"10.3233\/CH-189011_ref49","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/BF02308838","article-title":"Cardiovascular autonomic dysfunction in sickle cell anemia: A possible risk factor for sudden death?","volume":"7","author":"Romero Mestre","year":"1997","journal-title":"Clin Auton Res"},{"key":"10.3233\/CH-189011_ref50","first-page":"393","article-title":"Abnormal autonomic cardiovascular responses in patients with sickle cell anemia","volume":"40","author":"Romero-Vecchione","year":"1995","journal-title":"Sangre (Barc)"},{"key":"10.3233\/CH-189011_ref51","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1164\/rccm.201103-0537OC","article-title":"Peripheral vasoconstriction and abnormal parasympathetic response to sighs and transient hypoxia in sickle cell disease","volume":"184","author":"Sangkatumvong","year":"2011","journal-title":"Am J Respir Crit Care Med"},{"key":"10.3233\/CH-189011_ref52","first-page":"97","article-title":"Transport and peripheral bioactivities of nitrogen oxides carried by red blood cell hemoglob: Role in oxygen delivery","volume":"22","author":"Sonveaux","year":"2007","journal-title":"Physiology (Bethesda)"},{"key":"10.3233\/CH-189011_ref53","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1097\/NNR.0b013e3182186a21","article-title":"Autonomic nervous system reactivity: Children with and without sickle cell disease","volume":"60","author":"Treadwell","year":"2011","journal-title":"Nursing Research"},{"key":"10.3233\/CH-189011_ref54","doi-asserted-by":"crossref","first-page":"3047","DOI":"10.1073\/pnas.052522799","article-title":"Primary role for adherent leukocytes in sickle cell vascular occlusion: A new paradigm","volume":"99","author":"Turhan","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.3233\/CH-189011_ref55","doi-asserted-by":"crossref","first-page":"121","DOI":"10.3233\/BIR-2009-0532","article-title":"Mechanical stimulation of nitric oxide synthesizing mechanisms in erythrocytes","volume":"46","author":"Ulker","year":"2009","journal-title":"Biorheology"},{"key":"10.3233\/CH-189011_ref56","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.niox.2011.03.003","article-title":"Shear stress activation of nitric oxide synthase and increased nitric oxide levels in human red blood cells","volume":"24","author":"Ulker","year":"2011","journal-title":"Nitric Oxide: Biology and Chemistry\/Official Journal of the Nitric Oxide Society"},{"key":"10.3233\/CH-189011_ref57","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.niox.2009.03.004","article-title":"Role of hemoglobin oxygenation in the modulation of red blood cell mechanical properties by nitric oxide","volume":"21","author":"Uyuklu","year":"2009","journal-title":"Nitric Oxide"},{"key":"10.3233\/CH-189011_ref58","doi-asserted-by":"crossref","first-page":"37","DOI":"10.3233\/CH-131742","article-title":"Is there a relationship between the hematocrit-to-viscosity ratio and microvascular oxygenation in brain and muscle?","volume":"59","author":"Waltz","year":"2015","journal-title":"Clin Hemorheol Microcirc"},{"key":"10.3233\/CH-189011_ref59","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1182\/blood-2015-09-618538","article-title":"Neutrophils, platelets, and inflammatory pathways at the nexus of sickle cell disease pathophysiology","volume":"127","author":"Zhang","year":"2016","journal-title":"Blood"}],"container-title":["Clinical Hemorheology and Microcirculation"],"original-title":[],"link":[{"URL":"https:\/\/content.iospress.com\/download?id=10.3233\/CH-189011","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T15:06:42Z","timestamp":1777388802000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.medra.org\/servlet\/aliasResolver?alias=iospress&doi=10.3233\/CH-189011"}},"subtitle":[],"editor":[{"given":"P.","family":"Connes","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2018,3,28]]},"references-count":58,"journal-issue":{"issue":"2-3"},"URL":"https:\/\/doi.org\/10.3233\/ch-189011","relation":{},"ISSN":["1386-0291","1875-8622"],"issn-type":[{"value":"1386-0291","type":"print"},{"value":"1875-8622","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3,28]]}}}