{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T11:53:41Z","timestamp":1774439621863,"version":"3.50.1"},"reference-count":66,"publisher":"American Society of Hematology","issue":"1","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2004,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Much progress has been made during the past several decades in gaining understanding about the natural history of sickle cell disease and management approaches aimed at treating or even preventing certain disease complications. The characterization of the human genome now offers the opportunity to understand relationships regarding how gene polymorphisms as well as how environmental factors affect the sickle cell disease phenotype, i.e., the individual patient\u2019s overall clinical severity as well as their specific organ function. This chapter explores some of these recent advances in knowledge.<\/jats:p><jats:p>In Section I, Dr. Michael DeBaun characterizes the problem of silent stroke in sickle cell disease, comparing and contrasting its clinical and neuroimaging features with overt stroke. Combined, these events affect virtually 40% of children with sickle cell anemia. New understanding of risk factors, associated clinical findings, and imaging technologies are impacting substantially on treatment options. The appreciable cognitive dysfunction and other sequelae of silent infarct demand more effective treatments and ultimate prevention.<\/jats:p><jats:p>In Section II, Dr. Charles Quinn addresses the conundrum of why some patients with sickle cell disease do well whereas others fare poorly. Some risk factors have been known for years, based upon careful study of hundreds of patients by the Cooperative Study for Sickle Cell Disease and investigators studying the Jamaican newborn cohort. Other prognostic measures have only recently been defined. Dr. Quinn devotes special attention to stroke and chest syndrome as organ-related complications but also describes attempts to measure overall disease severity and to predict survival. Recently, investigators have attempted to predict factors responsible for early mortality in children and following onset of pulmonary hypertension in adults.<\/jats:p><jats:p>In Section III, Dr. Martin Steinberg reviews pharmacologic approaches to sickle cell disease and the rationale for their use. In addition to the inhibition of hemoglobin S polymerization, newer targets have been defined during the past one to two decades. These include the erythrocyte membrane, changes in the red cell intracellular content (especially loss of water), endothelial injury, and free radical production. Hydroxyurea treatment attracted the greatest interest, but many uncertainties remain about its long-term benefits and toxicities. Newer \u201canti-sickling\u201d agents such as decitabine and short-chain fatty acids also receive attention. Prevention of red cell dehydration, \u201canti-endothelial\u201d therapy, and marshaling the potentially beneficial effects of nitric oxide are other new and exciting approaches.<\/jats:p>","DOI":"10.1182\/asheducation-2004.1.35","type":"journal-article","created":{"date-parts":[[2004,11,20]],"date-time":"2004-11-20T02:03:01Z","timestamp":1100916181000},"page":"35-47","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":74,"title":["Sickle Cell Disease"],"prefix":"10.1182","volume":"2004","author":[{"given":"George R.","family":"Buchanan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael R.","family":"DeBaun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles T.","family":"Quinn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin H.","family":"Steinberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"234","reference":[{"key":"2020021215283571900_R1","doi-asserted-by":"crossref","unstructured":"Armstrong FD, Thompson RJ, Jr., Wang W, et al. Cognitive functioning and brain magnetic resonance imaging in children with sickle cell disease. Neuropsychology Committee of the Cooperative Study of Sickle Cell Disease. Pediatrics. 1996;97:864\u2013870.","DOI":"10.1542\/peds.97.6.864"},{"key":"2020021215283571900_R2","doi-asserted-by":"crossref","unstructured":"Craft S, Schatz J, Glauser TA, Lee B, DeBaun MR. Neuropsychologic effects of stroke in children with sickle cell anemia. J Pediatr. 1993;123:712\u2013717.","DOI":"10.1016\/S0022-3476(05)80844-3"},{"key":"2020021215283571900_R3","doi-asserted-by":"crossref","unstructured":"Miller ST, Macklin EA, Pegelow CH, et al. Silent infarction as a risk factor for overt stroke in children with sickle cell anemia: a report from the Cooperative Study of Sickle Cell Disease. 2001;139(3):385\u2013390.","DOI":"10.1067\/mpd.2001.117580"},{"key":"2020021215283571900_R4","doi-asserted-by":"crossref","unstructured":"Pegelow CH, Macklin EA, Moser FG, et al. Longitudinal changes in brain magnetic resonance imaging findings in children with sickle cell disease. Blood. 2002;99:3014\u20133018.","DOI":"10.1182\/blood.V99.8.3014"},{"key":"2020021215283571900_R5","doi-asserted-by":"crossref","unstructured":"Schatz J, Brown RT, Pascual JM, Hsu L, DeBaun MR. Poor school and cognitive functioning with silent cerebral infarcts and sickle cell disease. Neurology. 2001;56:1109\u20131111.","DOI":"10.1212\/WNL.56.8.1109"},{"key":"2020021215283571900_R6","doi-asserted-by":"crossref","unstructured":"Wang WC, Langston JW, Steen RG, et al. Abnormalities of the central nervous system in very young children with sickle cell anemia. J Pediatr. 1998;132:994\u2013998.","DOI":"10.1016\/S0022-3476(98)70397-X"},{"key":"2020021215283571900_R7","doi-asserted-by":"crossref","unstructured":"Kinney TR, Sleeper LA, Wang WC, et al. Silent cerebral infarcts in sickle cell anemia: a risk factor analysis. The Cooperative Study of Sickle Cell Disease. Pediatrics. 1999;103:640\u2013645.","DOI":"10.1542\/peds.103.3.640"},{"key":"2020021215283571900_R8","doi-asserted-by":"crossref","unstructured":"Hoppe C, Klitz W, Cheng S, et al. Gene interactions and stroke risk in children with sickle cell anemia. Blood. 2004;103:2391\u20132396.","DOI":"10.1182\/blood-2003-09-3015"},{"key":"2020021215283571900_R9","doi-asserted-by":"crossref","unstructured":"Miller ST, Macklin EA, Pegelow CH, et al. Silent infarction as a risk factor for overt stroke in children with sickle cell anemia: a report from the Cooperative Study of Sickle Cell Disease. J Pediatr. 2001;139:385\u2013390.","DOI":"10.1067\/mpd.2001.117580"},{"key":"2020021215283571900_R10","doi-asserted-by":"crossref","unstructured":"Miller ML. Treatment of systemic lupus erythematosus. Curr Opin Rheumatol. 1991;3:803\u2013808.","DOI":"10.1097\/00002281-199110000-00009"},{"key":"2020021215283571900_R11","doi-asserted-by":"crossref","unstructured":"Glauser TA, Siegel MJ, Lee BC, DeBaun MR. Accuracy of neurologic examination and history in detecting evidence of MRI-diagnosed cerebral infarctions in children with sickle cell hemoglobinopathy. J Child Neurol. 1995;10:88\u201392.","DOI":"10.1177\/088307389501000203"},{"key":"2020021215283571900_R12","doi-asserted-by":"crossref","unstructured":"Adams RJ, McKie VC, Hsu L, et al. Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial Doppler ultrasonography. N Engl J Med. 1998;339:5\u201311.","DOI":"10.1056\/NEJM199807023390102"},{"key":"2020021215283571900_R13","unstructured":"Moser FG, Miller ST, Bello JA. The spectrum of brain MR abnormalities in sickle-cell disease: a report from the cooperative study of sickle cell disease. Am J Neuroradiol. 1996;17:965\u2013972."},{"key":"2020021215283571900_R14","doi-asserted-by":"crossref","unstructured":"Brown RT, Davis PC, Lambert R, et al. Neurocognitive functioning and magnetic resonance imaging in children with sickle cell disease. J Pediatr Psychol. 2000;25:503\u2013513.","DOI":"10.1093\/jpepsy\/25.7.503"},{"key":"2020021215283571900_R15","doi-asserted-by":"crossref","unstructured":"Craft S, Schatz J, Glauser T, Lee B, DeBaun M. The effects of bifrontal stroke during childhood on visual attention: Evidence from children with sickle cell disease. Developmental Neuropsychology. 1994;10:285\u2013297.","DOI":"10.1080\/87565649409540584"},{"key":"2020021215283571900_R16","doi-asserted-by":"crossref","unstructured":"Brandling-Bennett E, White DA, Armstrong M, Christ SE, DeBaun MR. Patterns of verbal long-term and working memory performance reveal deficits in strategic processing in children with frontal infarcts related to sickle cell disease. Develop Neuropsychol. 2003;24:1\u201312","DOI":"10.1207\/S15326942DN2401_01"},{"key":"2020021215283571900_R17","doi-asserted-by":"crossref","unstructured":"White DA, Salorio CF, Schatz J, DeBaun M. Preliminary study of working memory in children with stroke related to sickle cell disease. J Clin Exper Neuropsychol. 2000;22:257\u2013264.","DOI":"10.1076\/1380-3395(200004)22:2;1-1;FT257"},{"key":"2020021215283571900_R18","doi-asserted-by":"crossref","unstructured":"Yerys BE, White DA, Salorio CF, McKinstry RC, Moinuddin A, DeBaun MR. Memory strategy training in children with cerebral infarcts related to sickle cell disease. J Pediatr Hematol\/Oncol. 2003;25:495\u2013498.","DOI":"10.1097\/00043426-200306000-00014"},{"key":"2020021215283571900_R19","doi-asserted-by":"crossref","unstructured":"Scothorn DJ, Price C, Schwartz D, et al. Risk of recurrent stroke in children with sickle cell disease receiving blood transfusion therapy for at least five years after initial stroke. J Pediatr. 2002;140:348\u2013354.","DOI":"10.1067\/mpd.2002.122498"},{"key":"2020021215283571900_R20","doi-asserted-by":"crossref","unstructured":"Pegelow CH, Wang W, Granger S, et al. Silent infarcts in children with sickle cell anemia and abnormal cerebral artery velocity. Arch Neurol. 2001;58:2017\u20132021.","DOI":"10.1001\/archneur.58.12.2017"},{"key":"2020021215283571900_R21","doi-asserted-by":"crossref","unstructured":"Bernaudin F, Verlhac S, Freard F, et al. Multicenter prospective study of children with sickle cell disease: radiographic and psychometric correlation. J Child Neurol. 2000;15:333\u2013343.","DOI":"10.1177\/088307380001500510"},{"key":"2020021215283571900_R22","doi-asserted-by":"crossref","unstructured":"Kirkham FJ, Prengler M, Hewes DK, Ganesan V. Risk factors for arterial ischemic stroke in children. J Child Neurol. 2000;15:299\u2013307.","DOI":"10.1177\/088307380001500506"},{"key":"2020021215283571900_R23","unstructured":"Ohene-Frempong K, Weiner SJ, Sleeper LA, et al. Cerebrovascular accidents in sickle cell disease: rates and risk factors. Blood. 1998;91:288\u2013294."},{"key":"2020021215283571900_R24","doi-asserted-by":"crossref","unstructured":"Wang WC, Gallagher DM, Pegelow CH, et al. Multicenter comparison of magnetic resonance imaging and transcranial Doppler ultrasonography in the evaluation of the central nervous system in children with sickle cell disease. J Pediatr Hematol Oncol. 2000;22:335\u2013339.","DOI":"10.1097\/00043426-200007000-00010"},{"key":"2020021215283571900_R25","doi-asserted-by":"crossref","unstructured":"Quinn CT, Miller ST. Risk factors and prediction of outcomes in children and adolescents with sickle cell anemia. Hematol Oncol Clin North Am. 2004. In press.","DOI":"10.1016\/j.hoc.2004.07.004"},{"key":"2020021215283571900_R26","doi-asserted-by":"crossref","unstructured":"Adams RJ, McKie VC, Hsu L, et al. Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial Doppler ultrasonography. N Engl J Med. 1998;339:5\u201311.","DOI":"10.1056\/NEJM199807023390102"},{"key":"2020021215283571900_R27","doi-asserted-by":"crossref","unstructured":"Miller ST, Macklin EA, Pegelow CH, et al. Silent infarction as a risk factor for overt stroke in children with sickle cell anemia: a report from the Cooperative Study of Sickle Cell Disease. J Pediatr. 2001;139:385\u2013390.","DOI":"10.1067\/mpd.2001.117580"},{"key":"2020021215283571900_R28","doi-asserted-by":"crossref","unstructured":"Driscoll MC, Hurlet A, Styles L, et al. Stroke risk in siblings with sickle cell anemia. Blood. 2003;101:2401\u20132404.","DOI":"10.1182\/blood.V101.6.2401"},{"key":"2020021215283571900_R29","doi-asserted-by":"crossref","unstructured":"Styles LA, Hoppe C, Klitz W, Vichinsky E, Lubin B, Trachtenberg E. Evidence for HLA-related susceptibility for stroke in children with sickle cell disease. Blood. 2000;95:3562\u20133567.","DOI":"10.1182\/blood.V95.11.3562"},{"key":"2020021215283571900_R30","doi-asserted-by":"crossref","unstructured":"Hoppe C, Klitz W, Noble J, Vigil L, Vichinsky E, Styles L. Distinct HLA associations by stroke subtype in children with sickle cell anemia. Blood. 2003;101:2865\u20132869.","DOI":"10.1182\/blood-2002-09-2791"},{"key":"2020021215283571900_R31","doi-asserted-by":"crossref","unstructured":"Hoppe C, Klitz W, Cheng S, et al. Gene interactions and stroke risk in children with sickle cell anemia. Blood. 2004;103:2391\u20132396.","DOI":"10.1182\/blood-2003-09-3015"},{"key":"2020021215283571900_R32","doi-asserted-by":"crossref","unstructured":"Taylor JGt, Tang DC, Savage SA, et al. Variants in the VCAM1 gene and risk for symptomatic stroke in sickle cell disease. Blood. 2002;100:4303\u20134309.","DOI":"10.1182\/blood-2001-12-0306"},{"key":"2020021215283571900_R33","doi-asserted-by":"crossref","unstructured":"Kirkham FJ, Hewes DK, Prengler M, Wade A, Lane R, Evans JP. Nocturnal hypoxaemia and central-nervous-system events in sickle-cell disease. Lancet. 2001;357:1656\u20131659.","DOI":"10.1016\/S0140-6736(00)04821-2"},{"key":"2020021215283571900_R34","doi-asserted-by":"crossref","unstructured":"Wierenga KJ, Serjeant BE, Serjeant GR. Cerebrovascular complications and parvovirus infection in homozygous sickle cell disease. J Pediatr. 2001;139:438\u2013442.","DOI":"10.1067\/mpd.2001.117070"},{"key":"2020021215283571900_R35","doi-asserted-by":"crossref","unstructured":"Styles LA, Aarsman AJ, Vichinsky EP, Kuypers FA. Secretory phospholipase A(2) predicts impending acute chest syndrome in sickle cell disease. Blood. 2000;96:3276\u20133278.","DOI":"10.1182\/blood.V96.9.3276"},{"key":"2020021215283571900_R36","doi-asserted-by":"crossref","unstructured":"Miller ST, Sleeper LA, Pegelow CH, et al. Prediction of adverse outcomes in children with sickle cell disease. N Engl J Med. 2000;342:83\u201389.","DOI":"10.1056\/NEJM200001133420203"},{"key":"2020021215283571900_R37","doi-asserted-by":"crossref","unstructured":"Quinn CT, Rogers ZR, Buchanan GR. Survival of children with sickle cell disease. Blood. 2004;103:4023\u20134027.","DOI":"10.1182\/blood-2003-11-3758"},{"key":"2020021215283571900_R38","doi-asserted-by":"crossref","unstructured":"Okpala I, Daniel Y, Haynes R, Odoemene D, Goldman J. Relationship between the clinical manifestations of sickle cell disease and the expression of adhesion molecules on white blood cells. Eur J Haematol. 2002;69:135\u2013144.","DOI":"10.1034\/j.1600-0609.2002.02775.x"},{"key":"2020021215283571900_R39","doi-asserted-by":"crossref","unstructured":"Gladwin MT, Sachdev V, Jison ML, et al. Pulmonary hypertension as a risk factor for death in patients with sickle cell disease. N Engl J Med. 2004;350:886\u2013895.","DOI":"10.1056\/NEJMoa035477"},{"key":"2020021215283571900_R40","doi-asserted-by":"crossref","unstructured":"Weatherall DJ. Phenotype-genotype relationships in monogenic disease: lessons from the thalassaemias. Nat Rev Genet. 2001;2:245\u2013255.","DOI":"10.1038\/35066048"},{"key":"2020021215283571900_R41","doi-asserted-by":"crossref","unstructured":"Steinberg MH. Management of sickle cell disease. N Engl J Med. 1999;340:1021\u20131030.","DOI":"10.1056\/NEJM199904013401307"},{"key":"2020021215283571900_R42","doi-asserted-by":"crossref","unstructured":"Cokic VP, Smith RD, Beleslin-Cokic BB, et al. Hydroxyurea induces fetal hemoglobin by the nitric oxide-dependent activation of soluble guanylyl cyclase. J Clin Invest. 2003;111:231\u2013239.","DOI":"10.1172\/JCI200316672"},{"key":"2020021215283571900_R43","doi-asserted-by":"crossref","unstructured":"Steinberg MH, Barton F, Castro O, et al. Effect of hydroxyurea on mortality and morbidity in adult sickle cell anemia: risks and benefits up to 9 years of treatment. JAMA. 2003;289:1645\u20131651.","DOI":"10.1001\/jama.289.13.1645"},{"key":"2020021215283571900_R44","doi-asserted-by":"crossref","unstructured":"Ware RE, Eggleston B, Redding-Lallinger R, et al. Predictors of fetal hemoglobin response in children with sickle cell anemia receiving hydroxyurea therapy. Blood. 2002;99:10\u201314.","DOI":"10.1182\/blood.V99.1.10"},{"key":"2020021215283571900_R45","doi-asserted-by":"crossref","unstructured":"Zimmerman SA, Schultz WH, Davis JS, et al. Sustained long-term hematologic efficacy of hydroxyurea at maximum tolerated dose in children with sickle cell disease. Blood. 2004;103:2039\u20132045.","DOI":"10.1182\/blood-2003-07-2475"},{"key":"2020021215283571900_R46","doi-asserted-by":"crossref","unstructured":"Ware RE, Zimmerman SA, Schultz WH. Hydroxyurea as an alternative to blood transfusions for the prevention of recurrent stroke in children with sickle cell disease. Blood. 1999;94:3022\u20133026.","DOI":"10.1182\/blood.V94.9.3022"},{"key":"2020021215283571900_R47","doi-asserted-by":"crossref","unstructured":"Fung EB, Barden EM, Kawchak DA, et al. Effect of hydroxyurea therapy on resting energy expenditure in children with sickle cell disease. J Pediatr Hematol Oncol. 2001;23:604\u2013608.","DOI":"10.1097\/00043426-200112000-00010"},{"key":"2020021215283571900_R48","doi-asserted-by":"crossref","unstructured":"Steinberg MH, Nagel RL, Brugnara C. Cellular effects of hydroxyurea in Hb SC disease. Br J Haematol. 1997;98:838\u2013844.","DOI":"10.1046\/j.1365-2141.1997.3173132.x"},{"key":"2020021215283571900_R49","doi-asserted-by":"crossref","unstructured":"Miller MK, Zimmerman SA, Schultz WH, Ware RE. Hydroxyurea therapy for pediatric patients with hemoglobin SC disease. J Pediatr Hematol Oncol. 2001;23:306\u2013308.","DOI":"10.1097\/00043426-200106000-00014"},{"key":"2020021215283571900_R50","doi-asserted-by":"crossref","unstructured":"Saunthararajah Y, Hillery CA, Lavelle D, et al. Effects of 5-aza-2\u2032-deoxycytidine on fetal hemoglobin levels, red cell adhesion, and hematopoietic differentiation in patients with sickle cell disease. Blood. 2003;102:3865\u20133870.","DOI":"10.1182\/blood-2003-05-1738"},{"key":"2020021215283571900_R51","doi-asserted-by":"crossref","unstructured":"Cao H, Stamatoyannopoulos G, Jung M. Induction of human gamma globin gene expression by histone deacetylase inhibitors. Blood. 2004;103:701\u2013709.","DOI":"10.1182\/blood-2003-02-0478"},{"key":"2020021215283571900_R52","unstructured":"Atweh GF, Sutton M, Nassif I, et al. Sustained induction of fetal hemoglobin by pulse butyrate therapy in sickle cell disease. Blood. 1999;93:1790\u20131797."},{"key":"2020021215283571900_R53","doi-asserted-by":"crossref","unstructured":"De Franceschi L, Bachir D, Galacteros F, et al. Oral magnesium pidolate: effects of long-term administration in patients with sickle cell disease. Br J Haematol. 2000;108:284\u2013289.","DOI":"10.1046\/j.1365-2141.2000.01861.x"},{"key":"2020021215283571900_R54","doi-asserted-by":"crossref","unstructured":"Orringer EP, Casella JF, Ataga KI, et al. Purified poloxamer 188 for treatment of acute vaso-occlusive crisis of sickle cell disease: A randomized controlled trial. JAMA. 2001;286:2099\u20132106.","DOI":"10.1001\/jama.286.17.2099"},{"key":"2020021215283571900_R55","doi-asserted-by":"crossref","unstructured":"Eberhardt RT, McMahon L, Duffy SJ, et al. Sickle cell anemia is associated with reduced nitric oxide bioactivity in peripheral conduit and resistance vessels. Am J Hematol. 2003;74:104\u2013111.","DOI":"10.1002\/ajh.10387"},{"key":"2020021215283571900_R56","doi-asserted-by":"crossref","unstructured":"Ou J, Ou Z, Jones DW, et al. L-4F, an apolipoprotein A-1 mimetic, dramatically improves vasodilation in hypercholesterolemia and sickle cell disease. Circulation. 2003;107:2337\u20132341.","DOI":"10.1161\/01.CIR.0000070589.61860.A9"},{"key":"2020021215283571900_R57","doi-asserted-by":"crossref","unstructured":"Ansell BJ, Navab M, Hama S, et al. Inflammatory\/antiinflammatory properties of high-density lipoprotein distinguish patients from control subjects better than high-density lipoprotein cholesterol levels and are favorably affected by simvastatin treatment. Circulation. 2003;108:2751\u20132756.","DOI":"10.1161\/01.CIR.0000103624.14436.4B"},{"key":"2020021215283571900_R58","doi-asserted-by":"crossref","unstructured":"Weiner DL, Hibberd PL, Betit P, et al. Preliminary assessment of inhaled nitric oxide for acute vaso-occlusive crisis in pediatric patients with sickle cell disease. JAMA. 2003;289:1136\u20131142.","DOI":"10.1001\/jama.289.9.1136"},{"key":"2020021215283571900_R59","doi-asserted-by":"crossref","unstructured":"Solovey AA, Solovey AN, Harkness J, Hebbel RP. Modulation of endothelial cell activation in sickle cell disease: a pilot study. Blood. 2001;97:1937\u20131941.","DOI":"10.1182\/blood.V97.7.1937"},{"key":"2020021215283571900_R60","doi-asserted-by":"crossref","unstructured":"Kaul DK, Liu XD, Choong S, et al. Anti-inflammatory therapy ameliorates leukocyte adhesion and microvascular flow abnormalities in transgenic sickle mice. Am J Physiol Heart Circ Physiol. 2004;287:H293\u2013301.","DOI":"10.1152\/ajpheart.01150.2003"},{"key":"2020021215283571900_R61","doi-asserted-by":"crossref","unstructured":"Kaul DK, Tsai HM, Liu XD, et al. Monoclonal antibodies to \u03b1V\u03b23 (7E3 and LM609) inhibit sickle red blood cell-endothelium interactions induced by platelet-activating factor. Blood. 2000;95:368\u2013374.","DOI":"10.1182\/blood.V95.2.368"},{"key":"2020021215283571900_R62","doi-asserted-by":"crossref","unstructured":"Barabino GA, Liu XD, Ewenstein BM, Kaul DK. Anionic polysaccharides inhibit adhesion of sickle erythrocytes to the vascular endothelium and result in improved hemodynamic behavior. Blood. 1999;93:1422\u20131429.","DOI":"10.1182\/blood.V93.4.1422"},{"key":"2020021215283571900_R63","doi-asserted-by":"crossref","unstructured":"Kaul DK, Liu X, Nagel RL. Ameliorating effects of fluorocarbon emulsion on sickle red blood cell-induced obstruction in an ex vivo vasculature. Blood. 2001;98:3128\u20133131.","DOI":"10.1182\/blood.V98.10.3128"},{"key":"2020021215283571900_R64","doi-asserted-by":"crossref","unstructured":"Turhan A, Jenab P, Bruhns P, et al. Intravenous immune globulin prevents venular vaso-occlusion in sickle cell mice by inhibiting leukocyte adhesion and the interactions between sickle erythrocytes and adherent leukocytes. Blood. 2004;103:2397\u20132400.","DOI":"10.1182\/blood-2003-07-2209"},{"key":"2020021215283571900_R65","doi-asserted-by":"crossref","unstructured":"Matsui NM, Varki A, Embury SH. Heparin inhibits the flow adhesion of sickle red blood cells to P-selectin. Blood. 2002;100:3790\u20133796.","DOI":"10.1182\/blood-2002-02-0626"},{"key":"2020021215283571900_R66","doi-asserted-by":"crossref","unstructured":"Solovey A, Kollander R, Shet A, et al. Endothelial cell expression of tissue factor in sickle mice is augmented by hypoxia\/reoxygenation and inhibited by lovastatin. Blood. 2004;104:840\u2013846. Epub 2004 Apr 08.","DOI":"10.1182\/blood-2003-10-3719"}],"container-title":["Hematology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ashpublications.org\/hematology\/article-pdf\/2004\/1\/35\/1634545\/035_047ash.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/ashpublications.org\/hematology\/article-pdf\/2004\/1\/35\/1634545\/035_047ash.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,30]],"date-time":"2023-04-30T10:31:28Z","timestamp":1682850688000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/hematology\/article\/2004\/1\/35\/18698\/Sickle-Cell-Disease"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,1,1]]},"references-count":66,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2004,1,1]]}},"URL":"https:\/\/doi.org\/10.1182\/asheducation-2004.1.35","relation":{},"ISSN":["1520-4391","1520-4383"],"issn-type":[{"value":"1520-4391","type":"print"},{"value":"1520-4383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,1,1]]}}}