| Popis: |
In von Willebrand disease (VWD), the most common inherited bleeding disorder, patients have a quantitative or qualitative defect of von Willebrand factor (VWF). VWD is widely misdiagnosed because both its diagnosis and classification involve several pitfalls. The complexity and heterogeneity of VWF, (pre)analytical variables, limited repertoire of laboratory tests, intra-individual variation, complex interpretation of results and lack of expertise contribute to the diagnostic challenge. To provide the reader of the general knowledge on VWD, background information regarding biosynthesis, structure and function of VWF and epidemiology, classification, diagnosis and treatment of the disease is provided. Subsequently, the various published articles are presented. Recent developments in VWD diagnosis and classification are highlighted. All available laboratory tests are described, including their mechanisms and pitfalls, and are reviewed whether they are able to improve the VWD characterization. Two new automated VWF:GPIb binding activity assays, HemosIL VWF:RCo (ISTH nomenclature VWF:GPIbR) and INNOVANCE VWF Ac (ISTH nomenclature VWF:GPIbM), are compared in an extensively typed VWD population to evaluate whether they are more able to clearly distinguish type 1 and 2 VWD by using the VWF:GPIb binding activity / VWF antigen ratio, and also whether they are able to improve the quality of diagnosis and subtyping of VWD within this VWD cohort. The semi-automatic Hydragel von Willebrand Factor multimer technique, after correlation with the "gold standard" method for VWD diagnosis, is standardized and quantified by the establishment of reference intervals. Finally, we discuss the cross-sectional studies in VWD which were set up in collaboration with the Czech Republic and Slovakia (University Hospital Brno and Bratislava, F.D. Roosevelt Hospital Banská Bystrica). These studies aim to improve the understanding of the VWD epidemiology and laboratory phenotype/genotype correlation. Pitfalls in VWD diagnosis and classification are also highlighted in these studies. Based on all our findings from this thesis, it is emphasized that for the most accurate and complete VWD diagnosis/classification, an extensive test panel, analyzing different aspects of VWF, is required. Methodologies with the best balance between accessibility and accuracy are recommended, with automated testing being preferred above more manual methods. However, the currently available diagnostic tests are not infallible, which means that often unreliable results can lead to a misdiagnosis. The VWD cohort studies provide unique information on the laboratory phenotype-genotype relationship in VWD, and on the presence of certain causal mutations in a specific geographic region, which invite comparisons with other regions. |
