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
Szederjesi, A; Baronciani, L; Budde, U et al. (2018) An international collaborative study to compare different von Willebrand factor glycoprotein Ib binding activity assays: the COMPASS-VWF study. J Thromb Haemost :
Baumgartner, C K; Mattson, J G; Weiler, H et al. (2017) Targeting factor VIII expression to platelets for hemophilia A gene therapy does not induce an apparent thrombotic risk in mice. J Thromb Haemost 15:98-109
Doruelo, A L; Haberichter, S L; Christopherson, P A et al. (2017) Clinical and laboratory phenotype variability in type 2M von Willebrand disease. J Thromb Haemost 15:1559-1566
Roberts, Jonathan C; Morateck, Patti A; Christopherson, Pamela A et al. (2016) Rapid discrimination of the phenotypic variants of von Willebrand disease. Blood 127:2472-80
Montgomery, Robert R (2016) The heads and the tails of malaria and VWF. Blood 127:1081-2
Flood, Veronica H; Christopherson, Pamela A; Gill, Joan Cox et al. (2016) Clinical and laboratory variability in a cohort of patients diagnosed with type 1 VWD in the United States. Blood 127:2481-8
Albánez, S; Ogiwara, K; Michels, A et al. (2016) Aging and ABO blood type influence von Willebrand factor and factor VIII levels through interrelated mechanisms. J Thromb Haemost 14:953-63
Obser, T; Ledford-Kraemer, M; Oyen, F et al. (2016) Identification and characterization of the elusive mutation causing the historical von Willebrand Disease type IIC Miami. J Thromb Haemost 14:1725-35
Chen, Yingyu; Schroeder, Jocelyn A; Chen, Juan et al. (2016) The immunogenicity of platelet-derived FVIII in hemophilia A mice with or without preexisting anti-FVIII immunity. Blood 127:1346-54
Pipe, Steven W; Montgomery, Robert R; Pratt, Kathleen P et al. (2016) Life in the shadow of a dominant partner: the FVIII-VWF association and its clinical implications for hemophilia A. Blood 128:2007-2016

Showing the most recent 10 out of 26 publications