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Clinical and laboratory variability in a cohort of patients diagnosed with type 1 VWD in the United States. Blood 2016 05 19;127(20):2481-8



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Pubmed Central ID




Scopus ID

2-s2.0-84974556876   68 Citations


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.

Author List

Flood VH, Christopherson PA, Gill JC, Friedman KD, Haberichter SL, Bellissimo DB, Udani RA, Dasgupta M, Hoffmann RG, Ragni MV, Shapiro AD, Lusher JM, Lentz SR, Abshire TC, Leissinger C, Hoots WK, Manco-Johnson MJ, Gruppo RA, Boggio LN, Montgomery KT, Goodeve AC, James PD, Lillicrap D, Peake IR, Montgomery RR


Veronica H. Flood MD Professor in the Pediatrics department at Medical College of Wisconsin
Kenneth D. Friedman MD Professor in the Medicine department at Medical College of Wisconsin
Robert R. Montgomery MD Adjunct Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Blood Coagulation Tests
Comparative Genomic Hybridization
Genetic Variation
Sequence Analysis, DNA
Surveys and Questionnaires
United States
Young Adult
von Willebrand Disease, Type 1
von Willebrand Factor