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Thromb Haemost 2000; 84(03): 401-409
DOI: 10.1055/s-0037-1614035
Commentary
Schattauer GmbH

von Willebrand Disease in a Pediatric-based Population - Comparison of Type 1 Diagnostic Criteria and Use of the PFA-100® and a von Willebrand Factor/Collagen-binding Assay

J.A. Dean
1   From the Division of Haematology/Oncology, Department of Paediatrics, University of Toronto, Toronto
,
V. S. Blanchette
1   From the Division of Haematology/Oncology, Department of Paediatrics, University of Toronto, Toronto
4   Department of Paediatrics, University of Toronto, Toronto
,
M. D. Carcao
1   From the Division of Haematology/Oncology, Department of Paediatrics, University of Toronto, Toronto
4   Department of Paediatrics, University of Toronto, Toronto
,
A. M. Stain
2   Department of Nursing, University of Toronto, Toronto
,
C. R. Sparling
3   Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, University of Toronto, Toronto
,
J. Siekmann
7   Baxter Hyland Immuno, Vienna, Austria
,
P. L. Turecek
7   Baxter Hyland Immuno, Vienna, Austria
,
D. Lillicrap
6   Departments of Pathology and Medicine, Queen’s University, Kingston, Ontario, Canada
,
M. L. Rand
1   From the Division of Haematology/Oncology, Department of Paediatrics, University of Toronto, Toronto
5   Department of Biochemistry, University of Toronto, Toronto
› Author AffiliationsWe thank Dr. Paul Foster for his insight and helpful comments regarding this work and Dr. Marian Packham for reading of the manuscript. We also acknowledge the technical assistance of Ms. Ingrid Neunteufl with the multimer analysis and the assistance of Mr. Lijing He with the correlation analyses. We thank Dade Behring Inc for providing the PFA-100 instrument and test cartridges, and International Technidyne Corp. for providing the Surgicutt and Surgicutt-Jr. bleeding time devices. D.L. is supported by a Career Investigator Award from the Heart and Stroke Foundation of Ontario.
Further Information

Publication History

Received 06 July 1999

Accepted after resubmission 15 March 2000

Publication Date:
14 December 2017 (online)

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Summary

Definitive diagnosis of type 1 von Willebrand Disease (VWD) remains a problem. Provisional consensus guidelines for the diagnosis of definite and possible type 1 VWD were prepared by the Scientific Subcommittee on von Willebrand factor (VWF) of the Scientific and Standardization Committee (SSC) of the International Society on Thrombosis and Haemostasis (ISTH) during the 1996 annual meeting for the specific purpose of further evaluation in retrospective and prospective studies by a Working Party on Diagnostic Criteria (1996 Annual Report of the SSC/ISTH Subcommittee on VWF). In the first phase of this study, we compared 2 definitions of type 1 VWD, each with 3 criteria: significant bleeding history, laboratory investigations, and family history. Using the ISTH consensus guidelines for type 1 VWD definition, significantly fewer patients were diagnosed with definite type 1 disease as compared to our “in house” Hospital for Sick Children (HSC) criteria (4 vs. 31). While we recognize that the provisional ISTH consensus guidelines were not intended for clinical use, we believe that the results of our studies are of interest and will assist in any future refinements to the ISTH guidelines.

In the second phase of this study, we investigated the utility of 2 new tests, a laboratory screening test and a functional test, for VWD in our well characterized, pediatric-based population. The Platelet Function Analyzer (PFA-100®) provides an in vitro measure of primary hemostasis under conditions of high shear, using disposable cartridges containing collagen and either epinephrine or ADP. All tested subjects with types 2 or 3 VWD had prolonged PFA-100 closure times (CTs) with both cartridge types (n = 17) and prolonged bleeding times (n = 14). In subjects with definite type 1 VWD, 20/24 (83%) had prolonged CTs with the collagen/ADP cartridge (19/24 (79%) with collagen/epinephrine), compared with 7/26 (27%) with prolonged bleeding times. In subjects with definite types 1, 2, or 3 VWD, collagen/ADP CTs were abnormal in 37/41 subjects, giving an overall sensitivity of 90%. With this high sensitivity, the PFA-100 is a better screening test for VWD than the bleeding time.

We also tested a VWF collagen-binding assay (VWF:CBA) as a functional test for VWF, in comparison with the more routinely-used ristocetin cofactor assay (VWF:RCo). The VWF:CBA is based on an ELISA technique, which has the potential to be more reproducible than the VWF:RCo. We found that the VWF:CBA detected 43/49 (88%) subjects with definite types 1, 2, or 3 VWD, performing as well as the VWF:RCo, that detected 42/48 (88%). We also showed that, used in conjunction with VWF antigen levels, the VWF:CBA may be useful in classification of VWD subtypes.

Key words

von Willebrand disease - pediatrics - PFA-100 - collagen-binding activity - type 1 von Willebrand disease

Presented in part at the 39th Annual Meeting of the American Society of Hematology, San Diego, CA, USA, December 1997.


 

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