title: Clinical and laboratory variability in a cohort of patients diagnosed with type 1 VWD in the United States.
abstract: von Willebrand disease (VWD) is the most common inherited bleeding disorder, and type 1 VWD is the most common VWD variant. Despite its frequency, diagnosis of type 1 VWD remains the subject of debate. In order to study the spectrum of type 1 VWD in the United States, the Zimmerman Program enrolled 482 subjects with a previous diagnosis of type 1 VWD without stringent laboratory diagnostic criteria. von Willebrand factor (VWF) laboratory testing and full-length VWF gene sequencing was performed for all index cases and healthy control subjects in a central laboratory. Bleeding phenotype was characterized using the International Society on Thrombosis and Haemostasis bleeding assessment tool. At study entry, 64% of subjects had VWF antigen (VWF:Ag) or VWF ristocetin cofactor activity below the lower limit of normal, whereas 36% had normal VWF levels. VWF sequence variations were most frequent in subjects with VWF:Ag <30 IU/dL (82%), whereas subjects with type 1 VWD and VWF:Ag ≥30 IU/dL had an intermediate frequency of variants (44%). Subjects whose VWF testing was normal at study entry had a similar rate of sequence variations as the healthy controls (14%). All subjects with severe type 1 VWD and VWF:Ag ≤5 IU/dL had an abnormal bleeding score (BS), but otherwise BS did not correlate with VWF:Ag. Subjects with a historical diagnosis of type 1 VWD had similar rates of abnormal BS compared with subjects with low VWF levels at study entry. Type 1 VWD in the United States is highly variable, and bleeding symptoms are frequent in this population.
authors: Division of Hematology/Oncology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI; Children's Research Institute, Children's Hospital of Wisconsin, Milwaukee, WI; Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI;
authors: Veronica H
authors: VH
authors: Flood
authors: Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI;
authors: Pamela A
authors: PA
authors: Christopherson
authors: Division of Hematology/Oncology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI; Children's Research Institute, Children's Hospital of Wisconsin, Milwaukee, WI; Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI;
authors: Joan Cox
authors: JC
authors: Gill
authors: Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI; Division of Hematology/Oncology, Department of Medicine, and.
authors: Kenneth D
authors: KD
authors: Friedman
authors: Division of Hematology/Oncology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI; Children's Research Institute, Children's Hospital of Wisconsin, Milwaukee, WI; Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI;
authors: Sandra L
authors: SL
authors: Haberichter
authors: Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI;
authors: Daniel B
authors: DB
authors: Bellissimo
authors: Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI;
authors: Rupa A
authors: RA
authors: Udani
authors: Division of Quantitative Health Sciences, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI;
authors: Mahua
authors: M
authors: Dasgupta
authors: Division of Quantitative Health Sciences, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI;
authors: Raymond G
authors: RG
authors: Hoffmann
authors: Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA;
authors: Margaret V
authors: MV
authors: Ragni
authors: Indiana Hemophilia and Thrombosis Center, Indianapolis, IN;
authors: Amy D
authors: AD
authors: Shapiro
authors: Division of Hematology, Children's Hospital of Michigan, Detroit, MI;
authors: Jeanne M
authors: JM
authors: Lusher
authors: Department of Internal Medicine, University of Iowa, Iowa City, IA;
authors: Steven R
authors: SR
authors: Lentz
authors: Division of Hematology/Oncology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI; Children's Research Institute, Children's Hospital of Wisconsin, Milwaukee, WI; Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI; Division of Hematology/Oncology, Department of Medicine, and Department of Pediatrics, Emory University School of Medicine, Atlanta, GA;
authors: Thomas C
authors: TC
authors: Abshire
authors: Departments of Medicine, Pediatrics, and Pathology, Tulane University School of Medicine, New Orleans, LA;
authors: Cindy
authors: C
authors: Leissinger
authors: Department of Pediatrics, University of Texas Health Science Center, Houston, TX;
authors: W Keith
authors: WK
authors: Hoots
authors: Mountain States Regional Hemophilia and Thrombosis Center, Aurora, CO;
authors: Marilyn J
authors: MJ
authors: Manco-Johnson
authors: Division of Hematology/Oncology, Cincinnati Children's Hospital, Cincinnati, OH;
authors: Ralph A
authors: RA
authors: Gruppo
authors: Rush Hemophilia and Thrombophilia Center, Rush University Medical Center, Chicago, IL;
authors: Lisa N
authors: LN
authors: Boggio
authors: Partners HealthCare Personalized Medicine, Cambridge, MA;
authors: Kate T
authors: KT
authors: Montgomery
authors: Haemostasis Research Group, Department of Cardiovascular Science, University of Sheffield, Sheffield, United Kingdom; and.
authors: Anne C
authors: AC
authors: Goodeve
authors: Departments of Medicine, and Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada.
authors: Paula D
authors: PD
authors: James
authors: Departments of Medicine, and Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada.
authors: David
authors: D
authors: Lillicrap
authors: Haemostasis Research Group, Department of Cardiovascular Science, University of Sheffield, Sheffield, United Kingdom; and.
authors: Ian R
authors: IR
authors: Peake
authors: Division of Hematology/Oncology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI; Children's Research Institute, Children's Hospital of Wisconsin, Milwaukee, WI; Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI;
authors: Robert R
authors: RR
authors: Montgomery
mesh_terms: D000293:Adolescent; D001780:Blood Coagulation Tests; D055028:Comparative Genomic Hybridization; D005260:Female; D014644:Genetic Variation; D006470:Hemorrhage / Q000209:etiology; D006801:Humans; D008297:Male; D010641:Phenotype; D017422:Sequence Analysis, DNA; D011795:Surveys and Questionnaires; D014481:United States / Q000453:epidemiology; D055815:Young Adult; D056725:von Willebrand Disease, Type 1 / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D014841:von Willebrand Factor / Q000032:analysis / Q000235:genetics
chemical_list: C029417:Von Willebrand antigen; D014841:von Willebrand Factor