title: Higher and lower active circulating VWF levels: different facets of von Willebrand disease.
abstract: Most circulating von Willebrand factor (VWF) is normally inactive and incapable of binding platelets, but numerous disorders may modify the proportion of active VWF. We explored active VWF levels in patients with von Willebrand disease (VWD) whose VWF had a higher affinity for platelet glycoprotein (GP)Ib, but different susceptibilities to ADAMTS13 and multimer patterns (9 patients lacking large multimers, 10 with a normal pattern); 12 patients with VWF C2362F and R1819_C1948delinsS mutations, which make VWF resistant to ADAMTS13 were also studied. Type 2B patients with abnormal or normal multimers had significantly more active VWF (3·33 ± 1·6 and 3·74 ± 0·74, respectively; normal 0·99 ± 0·23). The type of VWF mutation influenced VWF activation: V1316M was associated with the highest levels in patients with abnormal multimers, and R1341W in those with normal multimers. Pregnancy induced gradually rising active VWF levels and declining platelet counts in one type 2B VWD patient without large multimers. Active VWF levels dropped significantly in patients homozygous for the C2362F mutation or heterozygous for R1819_C1948delinsS mutations (0·2 ± 0·03 and 0·23 ± 0·1, respectively), and less in cases heterozygous for the VWF C2362F mutation (0·55 ± 0·17). We demonstrate that VWF may be more or less activated, with or without any direct involvement of the A1 domain, and regardless of ADAMTS13.
authors.affiliation: Department of Medicine, University of Padua Medical School, Padua, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Casonato
authors.affiliation: Department of Cardiologic, Thoracic and Vascular Sciences, University of Padua, Padua, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Pontara
authors.affiliation: Pharmaceutical Chemistry and Pharmacology Department, University of Padua, Padua, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Morpurgo
authors.affiliation: Department of Medicine, University of Padua Medical School, Padua, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Sartorello
authors.affiliation: Department of Clinical Chemistry and Haematology, University Medical Centre Utrecht, Utrecht, the Netherlands.
authors.forename: Philip G
authors.initials: PG
authors.lastname: De Groot
authors.affiliation: Department of Cardiologic, Thoracic and Vascular Sciences, University of Padua, Padua, Italy.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Cattini
authors.affiliation: Department of Cardiologic, Thoracic and Vascular Sciences, University of Padua, Padua, Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: Daidone
authors.affiliation: Department of Translational Research, Stem Cells Unit, IRCCS, C.R.O., Aviano, Italy.|Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Luigi
authors.initials: L
authors.lastname: De Marco
mesh_terms: D051722:ADAM Proteins / Q000502:physiology*; D000071120:ADAMTS13 Protein; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology; D005260:Female; D006490:Hemostatics / Q000494:pharmacology; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D009154:Mutation / Q000235:genetics*; D010974:Platelet Aggregation / Q000235:genetics; D010976:Platelet Count; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism*; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000235:genetics; D013921:Thrombocytopenia / Q000235:genetics; D014842:von Willebrand Diseases / Q000235:genetics*; D014841:von Willebrand Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D006490:Hemostatics; D019038:Platelet Glycoprotein GPIb-IX Complex; D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human; D003894:Deamino Arginine Vasopressin
keywords: VWF mutations; a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13; active von Willebrand factor; von Willebrand disease; von Willebrand factor