{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:33:26Z","timestamp":1791275606133,"version":"4.1.0"},"reference-count":50,"publisher":"Archives of Pathology and Laboratory Medicine","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,5]]},"abstract":"\n Context<\/jats:italic>\n .\u2014Vascular occlusion in sickle cell disease causes increased levels of plasma cell-free DNA as a result of cell death and tissue damage.\n <\/jats:p>\n \n Objectives<\/jats:italic>\n .\u2014This study investigates plasma cell-free DNA concentrations in sickle cell disease patients, and aims at exploring the significance of plasma cell-free DNA as a potential biomarker in predicting its complications.\n <\/jats:p>\n \n Design<\/jats:italic>\n .\u2014Plasma cell-free DNA levels were measured using real-time quantitative polymerase chain reaction to quantitatively measure \u03b2-globin gene in blood samples from 57 sickle cell disease patients with acute vaso-occlusive crisis, 42 patients in steady state, 16 individuals with sickle cell trait, and 40 healthy controls.\n <\/jats:p>\n \n Results<\/jats:italic>\n .\u2014Plasma cell-free DNA level was significantly elevated in samples from patients with acute vaso-occlusive crisis when compared with those in steady state (\n P<\/jats:italic>\n = .002), and was significantly higher both in crisis and in steady state when compared with individuals with sickle cell trait and healthy controls (\n P<\/jats:italic>\n < .001). There was no difference in cell-free DNA levels between individuals with sickle cell trait and healthy controls. There was no association between plasma cell-free DNA levels and various clinical complications of sickle cell disease and comorbidity.\n <\/jats:p>\n \n Conclusions<\/jats:italic>\n .\u2014Plasma cell-free DNA, as quantified by polymerase chain reaction amplification of the \u03b2-globin and human telomerase reverse transcriptase genes, is increased in sickle cell disease patients in vaso-occlusive crisis and in steady state compared with individuals with sickle cell trait and healthy controls, and may be used as a tool to diagnose and monitor the sickle cell crisis and differentiate post\u2013packed red cell transfusion sickle cell disease patients from individuals with sickle cell trait.\n <\/jats:p>","DOI":"10.5858\/arpa.2012-0725-oa","type":"journal-article","created":{"date-parts":[[2014,4,30]],"date-time":"2014-04-30T17:04:23Z","timestamp":1398877463000},"page":"678-683","source":"Crossref","is-referenced-by-count":19,"title":["Circulating Cell-Free DNA in Sickle Cell Disease: Is It a Potentially Useful Biomarker?"],"prefix":"10.5858","volume":"138","author":[{"given":"Salah","family":"Al-Humood","sequence":"first","affiliation":[{"name":"From the Department of Pathology, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajaa","family":"Zueriq","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lama","family":"Al-Faris","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajaa","family":"Marouf","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fahd","family":"Al-Mulla","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"3906","reference":[{"key":"i1543-2165-138-5-678-b01","series-title":"Sickle Cell Disease: Basic Principles and Clinical Practice","author":"Embury\n SH,","year":"1994","unstructured":"Embury\n SH, \n \n Hebbel\n RP, \n \n Mohandas\n N, \n \n Steinberg\n MH, \n \n eds. Sickle Cell Disease: Basic Principles and Clinical Practice. New York, NY: Raven Press;1994."},{"key":"i1543-2165-138-5-678-b02","series-title":"Sickle Cell Disease","author":"Serjeant\n GR,","year":"2001","unstructured":"Serjeant\n GR, \n \n Serjeant\n BE. \n \n Sickle Cell Disease. Oxford, United Kingdom: Oxford University Press;2001."},{"issue":"1","key":"i1543-2165-138-5-678-b03","series-title":"N Engl J Med","first-page":"11","article-title":"Pain in sickle cell disease: rates and risk factors","volume":"325","author":"Platt\n OS,","year":"1991","unstructured":"Platt\n OS, \n \n Thorington\n BD, \n \n Brambilla\n DJ, \n et al\n . Pain in sickle cell disease: rates and risk factors. 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C R Seances Soc Biol Fil. 1948;142(3\u20134):241\u2013243."},{"issue":"2","key":"i1543-2165-138-5-678-b06","series-title":"J Immunol Methods","first-page":"157","article-title":"Radioimmunoassay for nanogram quantities of DNA","volume":"9","author":"Leon\n SA,","year":"1975","unstructured":"Leon\n SA, \n \n Green\n A, \n \n Yaros\n MJ, \n \n Shapiro\n B. \n \n Radioimmunoassay for nanogram quantities of DNA. J Immunol Methods. 1975;9(2):157\u2013164."},{"issue":"3","key":"i1543-2165-138-5-678-b07","series-title":"Cancer Res","first-page":"646","article-title":"Free DNA in the serum of cancer patients and the effect of therapy","volume":"37","author":"Leon\n SA,","year":"1977","unstructured":"Leon\n SA, \n \n Shapiro\n B, \n \n Sklaroff\n DM, \n \n Yaros\n MJ. \n \n Free DNA in the serum of cancer patients and the effect of therapy. 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Pathology. 2007;39(2):197\u2013207."},{"issue":"11","key":"i1543-2165-138-5-678-b10","series-title":"Cancer","first-page":"2116","article-title":"Determination of circulating DNA levels in patients with benign or malignant gastrointestinal disease","volume":"51","author":"Shapiro\n B,","year":"1983","unstructured":"Shapiro\n B, \n \n Chakrabarty\n M, \n \n Cohn\n EM, \n \n Leon\n SA. \n \n Determination of circulating DNA levels in patients with benign or malignant gastrointestinal disease. Cancer. 1983;51(11):2116\u20132120."},{"issue":"3","key":"i1543-2165-138-5-678-b11","series-title":"Am J Med","first-page":"429","article-title":"Circulating DNA in systemic lupus erythematosus: isolation and characterization","volume":"67","author":"Steinman\n CR.","year":"1979","unstructured":"Steinman\n CR. \n \n Circulating DNA in systemic lupus erythematosus: isolation and characterization. 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J Clin Invest. 2000;106(3):411\u2013420."},{"issue":"3","key":"i1543-2165-138-5-678-b14","series-title":"Br J Haematol","first-page":"586","article-title":"The painful crisis of homozygous sickle cell disease: clinical features","volume":"87","author":"Serjeant\n GR,","year":"1994","unstructured":"Serjeant\n GR, \n \n Ceulaer, CD, \n \n Lethbridge\n R, \n \n Morris\n J, \n \n Singhal\n A, \n \n Thomas\n PW. \n \n The painful crisis of homozygous sickle cell disease: clinical features. Br J Haematol. 1994;87(3):586\u2013591."},{"issue":"4","key":"i1543-2165-138-5-678-b15","series-title":"Am J Hum Genet","first-page":"768","article-title":"Quantitative analysis of fetal DNA in maternal plasma and serum: implications for noninvasive prenatal diagnosis","volume":"62","author":"Lo\n YM,","year":"1998","unstructured":"Lo\n YM, \n \n Tein\n MS, \n \n Lau\n TK, \n et al\n . Quantitative analysis of fetal DNA in maternal plasma and serum: implications for noninvasive prenatal diagnosis. Am J Hum Genet. 1998;62(4):768\u2013775."},{"issue":"10","key":"i1543-2165-138-5-678-b16","series-title":"Clin Chem","first-page":"1741","article-title":"Presence of donor- and recipient-derived DNA in cell-free urine samples of renal transplantation recipients: urinary DNA chimerism","volume":"45","author":"Zhang\n J,","year":"1999","unstructured":"Zhang\n J, \n \n Tong\n KL, \n \n Li\n PK, \n et al\n . Presence of donor- and recipient-derived DNA in cell-free urine samples of renal transplantation recipients: urinary DNA chimerism. Clin Chem. 1999;45(10):1741\u20131746."},{"issue":"9076","key":"i1543-2165-138-5-678-b17","series-title":"Lancet","first-page":"485","article-title":"Presence of fetal DNA in maternal plasma and serum","volume":"350","author":"Lo\n YM,","year":"1997","unstructured":"Lo\n YM, \n \n Corbetta\n N, \n \n Chamberlain\n PF, \n et al\n . Presence of fetal DNA in maternal plasma and serum. Lancet. 1997;350(9076):485\u2013487."},{"issue":"2","key":"i1543-2165-138-5-678-b18","series-title":"Cancer Lett","first-page":"221","article-title":"Plasma DNA as a marker of cancerous cell death: investigations in patients suffering from lung cancer and in nude mice bearing human tumours","volume":"91","author":"Fournie\n GJ,","year":"1995","unstructured":"Fournie\n GJ, \n \n Courtin\n JP, \n \n Laval\n F, \n et al\n . Plasma DNA as a marker of cancerous cell death: investigations in patients suffering from lung cancer and in nude mice bearing human tumours. Cancer Lett. 1995;91(2):221\u2013227."},{"issue":"21","key":"i1543-2165-138-5-678-b19","series-title":"J Clin Oncol","first-page":"3902","article-title":"Quantification of free circulating DNA as a diagnostic marker in lung cancer","volume":"21","author":"Sozzi\n G,","year":"2003","unstructured":"Sozzi\n G, \n \n Conte\n D, \n \n Leon\n M, \n et al\n . Quantification of free circulating DNA as a diagnostic marker in lung cancer. J Clin Oncol. 2003;21(21):3902\u20133908."},{"issue":"2\u20133","key":"i1543-2165-138-5-678-b20","series-title":"Mutat Res","first-page":"105","article-title":"Circulating free DNA in plasma or serum as biomarker of carcinogenesis: practical aspects and biological significance","volume":"635","author":"Gormally\n E,","year":"2007","unstructured":"Gormally\n E, \n \n Caboux\n E, \n \n Vineis\n P, \n \n Hainaut\n P. \n \n Circulating free DNA in plasma or serum as biomarker of carcinogenesis: practical aspects and biological significance. Mutat Res. 2007;635(2\u20133):105\u2013117."},{"issue":"8, pt 1","key":"i1543-2165-138-5-678-b21","series-title":"Clin Chem","first-page":"1078","article-title":"Genetic analysis of DNA excreted in urine: a new approach for detecting specific genomic DNA sequences from cells dying in an organism","volume":"46","author":"Botezatu\n I,","year":"2000","unstructured":"Botezatu\n I, \n \n Serdyuk\n O, \n \n Potapova\n G, \n et al\n . Genetic analysis of DNA excreted in urine: a new approach for detecting specific genomic DNA sequences from cells dying in an organism. Clin Chem. 2000;46(8, pt 1):1078\u20131084."},{"issue":"9","key":"i1543-2165-138-5-678-b22","series-title":"Am J Epidemiol","first-page":"839","article-title":"Sickle hemoglobin (Hb S) allele and sickle cell disease: a HuGE review","volume":"151","author":"Ashley-Koch\n A,","year":"2000","unstructured":"Ashley-Koch\n A, \n \n Yang\n Q, \n \n Olney\n RS. \n \n Sickle hemoglobin (Hb S) allele and sickle cell disease: a HuGE review. Am J Epidemiol. 2000;151(9):839\u2013845."},{"issue":"5","key":"i1543-2165-138-5-678-b23","series-title":"Br J Haematol","first-page":"738","article-title":"Cell-free DNA levels in pregnancies at risk of sickle cell disease and significant ethnic variation","volume":"135","author":"Gerovassili\n A,","year":"2006","unstructured":"Gerovassili\n A, \n \n Nicolaides\n KH, \n \n Thein\n SL, \n \n Rees\n DC. \n \n Cell-free DNA levels in pregnancies at risk of sickle cell disease and significant ethnic variation. Br J Haematol. 2006;135(5):738\u2013741."},{"issue":"3","key":"i1543-2165-138-5-678-b24","series-title":"Pain Manag Nurs","first-page":"106","article-title":"Temperature changes, temperature extremes, and their relationship to emergency department visits and hospitalizations for sickle cell crisis","volume":"4","author":"Smith\n WR,","year":"2003","unstructured":"Smith\n WR, \n \n Coyne\n P, \n \n Smith\n VS, \n \n Mercier\n B. \n \n Temperature changes, temperature extremes, and their relationship to emergency department visits and hospitalizations for sickle cell crisis. Pain Manag Nurs. 2003;4(3):106\u2013111."},{"issue":"1","key":"i1543-2165-138-5-678-b25","series-title":"Blood","first-page":"317","article-title":"Fragment D-dimer levels: an objective marker of vaso-occlusive crisis and other complications of sickle cell disease","volume":"68","author":"Devine\n DV,","year":"1986","unstructured":"Devine\n DV, \n \n Kinney\n TR, \n \n Thomas\n PF, \n \n Rosse\n WF, \n \n Greenberg\n CS. \n \n Fragment D-dimer levels: an objective marker of vaso-occlusive crisis and other complications of sickle cell disease. Blood. 1986;68(1):317\u2013319."},{"key":"i1543-2165-138-5-678-b01","series-title":"Sickle Cell Disease: Basic Principles and Clinical Practice","author":"Embury\n SH,","year":"1994","unstructured":"Embury\n SH, \n \n Hebbel\n RP, \n \n Mohandas\n N, \n \n Steinberg\n MH, \n \n eds. Sickle Cell Disease: Basic Principles and Clinical Practice. 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Pathology. 2007;39(2):197\u2013207."},{"issue":"11","key":"i1543-2165-138-5-678-b10","series-title":"Cancer","first-page":"2116","article-title":"Determination of circulating DNA levels in patients with benign or malignant gastrointestinal disease","volume":"51","author":"Shapiro\n B,","year":"1983","unstructured":"Shapiro\n B, \n \n Chakrabarty\n M, \n \n Cohn\n EM, \n \n Leon\n SA. \n \n Determination of circulating DNA levels in patients with benign or malignant gastrointestinal disease. Cancer. 1983;51(11):2116\u20132120."},{"issue":"3","key":"i1543-2165-138-5-678-b11","series-title":"Am J Med","first-page":"429","article-title":"Circulating DNA in systemic lupus erythematosus: isolation and characterization","volume":"67","author":"Steinman\n CR.","year":"1979","unstructured":"Steinman\n CR. \n \n Circulating DNA in systemic lupus erythematosus: isolation and characterization. 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Lancet. 1997;350(9076):485\u2013487."},{"issue":"2","key":"i1543-2165-138-5-678-b18","series-title":"Cancer Lett","first-page":"221","article-title":"Plasma DNA as a marker of cancerous cell death: investigations in patients suffering from lung cancer and in nude mice bearing human tumours","volume":"91","author":"Fournie\n GJ,","year":"1995","unstructured":"Fournie\n GJ, \n \n Courtin\n JP, \n \n Laval\n F, \n et al\n . Plasma DNA as a marker of cancerous cell death: investigations in patients suffering from lung cancer and in nude mice bearing human tumours. Cancer Lett. 1995;91(2):221\u2013227."},{"issue":"21","key":"i1543-2165-138-5-678-b19","series-title":"J Clin Oncol","first-page":"3902","article-title":"Quantification of free circulating DNA as a diagnostic marker in lung cancer","volume":"21","author":"Sozzi\n G,","year":"2003","unstructured":"Sozzi\n G, \n \n Conte\n D, \n \n Leon\n M, \n et al\n . Quantification of free circulating DNA as a diagnostic marker in lung cancer. 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Genetic analysis of DNA excreted in urine: a new approach for detecting specific genomic DNA sequences from cells dying in an organism. Clin Chem. 2000;46(8, pt 1):1078\u20131084."},{"issue":"9","key":"i1543-2165-138-5-678-b22","series-title":"Am J Epidemiol","first-page":"839","article-title":"Sickle hemoglobin (Hb S) allele and sickle cell disease: a HuGE review","volume":"151","author":"Ashley-Koch\n A,","year":"2000","unstructured":"Ashley-Koch\n A, \n \n Yang\n Q, \n \n Olney\n RS. \n \n Sickle hemoglobin (Hb S) allele and sickle cell disease: a HuGE review. 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