17 research outputs found
Clinical and laboratory variability in a cohort of patients diagnosed with type 1 VWD in the United States
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 much 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. VWF laboratory testing and full length VWF
gene sequencing were performed for all index cases and healthy control subjects in a central
laboratory. Bleeding phenotype was characterized using the ISTH Bleeding Assessment Tool.
At study entry, 64% of subjects had VWF:Ag or VWF:RCo below the lower limit of normal,
while 36% had normal VWF levels. VWF sequence variations were most frequent in subjects
with VWF:Ag < 30 IU/dL (82%) while 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 at 14% of subjects. All
subjects with severe type 1 VWD and VWF:Ag ≤ 5 IU/dL had an abnormal bleeding score, but
otherwise bleeding score did not correlate with VWF:Ag level. Subjects with a historical
diagnosis of type 1 VWD had similar rates of abnormal bleeding scores compared to 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