Journal article
Clinical and laboratory variability in a cohort of patients diagnosed with type 1 VWD in the United States
Blood, Vol.127(20), pp.2481-2488
05/19/2016
DOI: 10.1182/blood-2015-10-673681
PMCID: PMC4874228
PMID: 26862110
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.
Details
- Title: Subtitle
- Clinical and laboratory variability in a cohort of patients diagnosed with type 1 VWD in the United States
- Creators
- Veronica H Flood - 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, WIPamela A Christopherson - Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WIJoan Cox Gill - 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, WIKenneth D Friedman - Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI; Division of Hematology/Oncology, Department of Medicine, andSandra L Haberichter - 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, WIDaniel B Bellissimo - Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WIRupa A Udani - Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WIMahua Dasgupta - Division of Quantitative Health Sciences, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WIRaymond G Hoffmann - Division of Quantitative Health Sciences, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WIMargaret V Ragni - Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh, Pittsburgh, PAAmy D Shapiro - Indiana Hemophilia and Thrombosis Center, Indianapolis, INJeanne M Lusher - Division of Hematology, Children's Hospital of Michigan, Detroit, MISteven R Lentz - Department of Internal Medicine, University of Iowa, Iowa City, IAThomas C Abshire - 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, GACindy Leissinger - Departments of Medicine, Pediatrics, and Pathology, Tulane University School of Medicine, New Orleans, LAW Keith Hoots - Department of Pediatrics, University of Texas Health Science Center, Houston, TXMarilyn J Manco-Johnson - Mountain States Regional Hemophilia and Thrombosis Center, Aurora, CORalph A Gruppo - Division of Hematology/Oncology, Cincinnati Children's Hospital, Cincinnati, OHLisa N Boggio - Rush Hemophilia and Thrombophilia Center, Rush University Medical Center, Chicago, ILKate T Montgomery - Partners HealthCare Personalized Medicine, Cambridge, MAAnne C Goodeve - Haemostasis Research Group, Department of Cardiovascular Science, University of Sheffield, Sheffield, United Kingdom; andPaula D James - Departments of Medicine, and Pathology and Molecular Medicine, Queen's University, Kingston, ON, CanadaDavid Lillicrap - Departments of Medicine, and Pathology and Molecular Medicine, Queen's University, Kingston, ON, CanadaIan R Peake - Haemostasis Research Group, Department of Cardiovascular Science, University of Sheffield, Sheffield, United Kingdom; andRobert R Montgomery - 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
- Resource Type
- Journal article
- Publication Details
- Blood, Vol.127(20), pp.2481-2488
- DOI
- 10.1182/blood-2015-10-673681
- PMID
- 26862110
- PMCID
- PMC4874228
- NLM abbreviation
- Blood
- ISSN
- 0006-4971
- eISSN
- 1528-0020
- Grant note
- R01 HL112614 / NHLBI NIH HHS P01 HL081588 / NHLBI NIH HHS K08 HL102260 / NHLBI NIH HHS
- Language
- English
- Date published
- 05/19/2016
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984094387302771
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