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Blood. 2016 May 19;127(20):2481-8. doi: 10.1182/blood-2015-10-673681. Epub 2016 Feb 9.

Clinical and laboratory variability in a cohort of patients diagnosed with type 1 VWD in the United States.

Author information

1
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;
2
Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI;
3
Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI; Division of Hematology/Oncology, Department of Medicine, and.
4
Division of Quantitative Health Sciences, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI;
5
Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA;
6
Indiana Hemophilia and Thrombosis Center, Indianapolis, IN;
7
Division of Hematology, Children's Hospital of Michigan, Detroit, MI;
8
Department of Internal Medicine, University of Iowa, Iowa City, IA;
9
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;
10
Departments of Medicine, Pediatrics, and Pathology, Tulane University School of Medicine, New Orleans, LA;
11
Department of Pediatrics, University of Texas Health Science Center, Houston, TX;
12
Mountain States Regional Hemophilia and Thrombosis Center, Aurora, CO;
13
Division of Hematology/Oncology, Cincinnati Children's Hospital, Cincinnati, OH;
14
Rush Hemophilia and Thrombophilia Center, Rush University Medical Center, Chicago, IL;
15
Partners HealthCare Personalized Medicine, Cambridge, MA;
16
Haemostasis Research Group, Department of Cardiovascular Science, University of Sheffield, Sheffield, United Kingdom; and.
17
Departments of Medicine, and Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada.

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.

Comment in

PMID:
26862110
PMCID:
PMC4874228
DOI:
10.1182/blood-2015-10-673681
[Indexed for MEDLINE]
Free PMC Article

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