title: ADAMTS13 activity in sickle cell disease.
abstract: Sickle red blood cell (SRBC)-endothelial adhesion plays a central role in sickle cell disease (SCD)-related vaso-occlusion. As unusually large von Willebrand factor (ULVWF) multimers mediate SRBC-endothelial adhesion, we investigated the activity of ADAMTS13, the metalloprotease responsible for cleaving ULVWF multimers, in SCD. ADAMTS13 activity was determined using a quantitative immunoblotting assay. VWF:Ag and VWF:RCo were determined using commercial assays. The high-molecular-weight VWF multimer percentage was determined by employing gel electrophoresis. ADAMTS13 activity was similar among asymptomatic patients (n = 8), patients at presentation with a painful crisis (n = 23), and healthy controls. ADAMTS13/VWF:Ag ratios were lower in patients compared to healthy HbAA controls, with the lowest values at presentation with a painful crisis (P = 0.02). Division of samples in those with VWF:RCo/VWF:Ag ratios < 0.70 and those with ratios >or= 0.70 revealed significantly more samples with ratios >or= 0.70 (P = 0.01) collected during painful crises. ULVWF multimers were detected in 6 patient samples and in 1 control sample. ADAMTS13/VWF:Ag ratios were inversely related to the duration of symptoms at presentation with an acute vaso-occlusive event (r(s)-0.67, P = 0.002). Although SCD is characterized by elevated VWF:Ag levels, no severe ADAMTS13 deficiency was detected in our patients.
authors.affiliation: Department of Internal Medicine, Slotervaart Hospital, Amsterdam, The Netherlands. jschnog@xs4all.nl
authors.forename: John-John B
authors.initials: JJ
authors.lastname: Schnog
authors.forename: Johanna A
authors.initials: JA
authors.lastname: Kremer Hovinga
authors.forename: Soraya
authors.initials: S
authors.lastname: Krieg
authors.forename: Sakir
authors.initials: S
authors.lastname: Akin
authors.forename: Bernhard
authors.initials: B
authors.lastname: Lämmle
authors.forename: Dees P M
authors.initials: DP
authors.lastname: Brandjes
authors.forename: Melvin R
authors.initials: MR
authors.lastname: Mac Gillavry
authors.forename: Fred D
authors.initials: FD
authors.lastname: Muskiet
authors.forename: Ashley J
authors.initials: AJ
authors.lastname: Duits
mesh_terms: D051722:ADAM Proteins / Q000097:blood* / Q000172:deficiency; D000071120:ADAMTS13 Protein; D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood* / Q000150:complications / Q000201:enzymology / Q000473:pathology; D015153:Blotting, Western; D002448:Cell Adhesion; D002648:Child; D004730:Endothelium, Vascular / Q000201:enzymology / Q000473:pathology; D004913:Erythrocytes, Abnormal / Q000201:enzymology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009097:Multienzyme Complexes / Q000097:blood; D010146:Pain / Q000209:etiology; D014652:Vascular Diseases / Q000097:blood / Q000209:etiology; D014841:von Willebrand Factor / Q000032:analysis
chemical_list: D009097:Multienzyme Complexes; D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human