74 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
The common VWF single nucleotide variants c.2365A>G and c.2385T>C modify VWF biosynthesis and clearance
Thrombosis and Hemostasi
Intragenic dinucleotide repeats in factor VIII gene for the diagnosis of haemophilia A
Two multi-allelic microsatellite polymorphisms within the factor VIII gene were studied in 138 Chinese subjects. The allele sizes detected were higher than those found in Caucasian populations, whereas the heterozygosity rates were lower, being 0.5370 for intron 13 and 0.4444 for intron 22 repeats respectively. Their usefulness in diagnosis was compared to other intragenic and extragenic RELPs, using previous data on the same 31 unrelated haemophilia A families. These intragenic microsatellite repeat polymorphisms were only informative for 18/31 families (58%); however, with the combined use of all existing RFLPs, the cumulative informativeness would be 100%.link_to_subscribed_fulltex
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