title: The rate of hemolysis in sickle cell disease correlates with the quantity of active von Willebrand factor in the plasma.
abstract: Vaso-occlusion, hemolysis, and oxidative stress are hallmarks of sickle cell disease (SCD). This pathology is accompanied by systemic endothelial activation, rendering the endothelium more adhesive for blood cells, including sickle erythrocytes. Activated endothelial cells display or secrete several adhesive molecules, including von Willebrand factor (VWF). We assessed several VWF parameters in SCD patients at baseline: multimer pattern, antigen concentration (VWF:Ag), activation factor (VWF:AF), and total active VWF (VWF:TA). VWF:AF was determined using a llama nanobody (AU/VWFa-11) that detects a platelet-binding conformation of the A1 domain; VWF:TA was calculated by multiplying VWF:Ag by VWF:AF. SCD plasma contained elevated VWF:Ag and ultralarge VWF multimers. VWF:TA, a measure of total VWF reactivity, correlated closely with hemolysis, as determined by serum lactate dehydrogenase. ADAMTS13 activity and antigen were normal in all patients. These findings suggest an important role for hyperreactive VWF in SCD pathology and connect SCD to other microangiopathies, particularly thrombotic thrombocytopenic purpura.
authors.affiliation: Research Division, Puget Sound Blood Center, 921 Terry Avenue, Seattle, WA 98104, USA.
authors.forename: Junmei
authors.initials: J
authors.lastname: Chen
authors.forename: William E
authors.initials: WE
authors.lastname: Hobbs
authors.forename: Jennie
authors.initials: J
authors.lastname: Le
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Lenting
authors.forename: Philip G
authors.initials: PG
authors.lastname: de Groot
authors.forename: José A
authors.initials: JA
authors.lastname: López
mesh_terms: D051722:ADAM Proteins / Q000097:blood / Q000378:metabolism; D000071120:ADAMTS13 Protein; D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood* / Q000378:metabolism / Q000473:pathology*; D001774:Blood Chemical Analysis; D005260:Female; D006461:Hemolysis / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D046912:Multiprotein Complexes / Q000032:analysis / Q000097:blood / Q000378:metabolism; D010949:Plasma / Q000737:chemistry; D055503:Protein Multimerization; D055815:Young Adult; D014841:von Willebrand Factor / Q000032:analysis / Q000378:metabolism*
chemical_list: D046912:Multiprotein Complexes; D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human