Von Willebrand Disease is a commonly diagnosed bleeding disorder that has recently come under scientific scrutiny for being under diagnosed in some groups (menorrhagia) at the same time it may be over diagnosed in others (up to 1-2% of the population). Retrospective studies have been done in the US, Canada, UK, and EU suggesting that the diagnosis of VWD is usually incontrovertible when levels of VWF are less than 30 IU/dL. Frequently, VWD is diagnosed when 1 VWF test is below the normal range (<50 IU/dL). Using the stringent level of 30 IU/dL, 69% of 548 VWD index cases, on restudy did not have reduced VWF:Ag or VWF:RCo. This proposal will study prospectively a large cohort of individuals referred to hematologists at one of 9 participating Centers and study the correlation of local diagnostic testing to central testing on repetitive study over a 5 year period. For the fist 2 years, this testing will be blinded and these results compared to similar testing over the next 2 3 years when there will be unblinded central testing and active quality control program between these institutions. Variant (type 2) VWD is diagnosed in 15-20% of individuals with VWD. New screening tests and a new VWF-phenotyping test will be developed and evaluated in this prospective study. Several quantitative bleeding scores (QBS) have been developed that help to differentiate subjects with VWD from those without VWD, but they have not been utilized to assess actual bleeding risk. Two large cohorts, one adult and one pediatric, will be studied with several QBS and these scores compared to their risk of hemorrhage prospectively. This project proposes to improve the fidelity, cost effectiveness, and sensitivity needed to diagnose VWD

Public Health Relevance

The diagnosis of von Willebrand Disease (VWD) is a public health issue both because of its under-diagnosis particularly in women with menorrhagia;and its over-diagnosis. The fidelity of VWD diagnosis must be examined because of the quality VWD laboratory testing and because many clinicians use a normal range of +2 SD that pre-determines 2.5% of the population as having low VWF. This project is focused on improving the fidelity, clinical utility, and comparative effectiveness of VWD diagnosis in subjects being evaluated for a clinical bleeding disorder.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL112614-01A1
Application #
8579411
Study Section
Special Emphasis Panel (ZRG1-VH-J (02))
Program Officer
Link, Rebecca P
Project Start
2013-09-01
Project End
2017-05-31
Budget Start
2013-09-01
Budget End
2014-05-31
Support Year
1
Fiscal Year
2013
Total Cost
$781,263
Indirect Cost
$43,259
Name
Medical College of Wisconsin
Department
Pediatrics
Type
Schools of Medicine
DUNS #
937639060
City
Milwaukee
State
WI
Country
United States
Zip Code
53226
Elbatarny, M; Mollah, S; Grabell, J et al. (2014) Normal range of bleeding scores for the ISTH-BAT: adult and pediatric data from the merging project. Haemophilia 20:831-5