title: Quantitative impact of using different criteria for the laboratory diagnosis of type 1 von Willebrand disease.
abstract: BACKGROUND
  Only ± 50% of patients with type 1 von Willebrand disease (VWD) have recognized molecular defects and diagnosis still rests on demonstrating low plasma von Willebrand factor (VWF) protein/function. However, no generalized consensus exists regarding the type and number of VWF variables that should be considered for diagnosis.
  
  
  OBJECTIVE
  To compare the quantitative impact of four different criteria to diagnose type 1 VWD.
  
  
  METHODS
  We tested four laboratory criteria on 4298 laboratory studies during a 5-year period. The first was the National Heart, Lung, and Blood Institute recommendation, which diagnoses type 1 VWD with plasma VWF antigen (VWF:Ag) and VWF ristocetin cofactor (VWF:RCo) < 30 IU dL(-1) and possible VWD/'low VWF' with values between 30 and 50 IU dL(-1) . Second, diagnosis was established when two of three variables, VWF:Ag, VWF:RCo, VWF collagen binding assay (VWF:CB), were ≤ 2.5th percentile. Diagnostic criterion for possible VWD/'low VWF' using percentiles was also described. The third criterion (European Group on von Willebrand Disease, EUVWD), uses a plasma level of VWF:RCo (or VWF:CB) ≤ 40 IU dL(-1) for diagnosis. Finally, the Zimmerman Program for the Molecular and Clinical Biology of VWD (ZPMCBVWD) diagnoses VWD if VWF:Ag or VWF:RCo are ≤ 40 IU dL(-1) .
  
  
  RESULTS
  The three assays had high correlation and excellent agreement at levels < 120 IU dL(-1) . The National Heart, Lung, and Blood Institute recommendation was followed to diagnose 122 (2.8%) patients with type 1 VWD and 704 (16.4%) with possible VWD/'low VWF.' Using percentiles, the diagnosis of type 1 VWD increased to 280 (6.5%) patients; 169 (3.9%) patients had possible VWD and 180 (4.2%) patients had 'low VWF.' Diagnoses using EUVWD and ZPMCBVWD criteria increased to 339 (7.9%) and 357 (8.3%) patients, respectively.
  
  
  CONCLUSIONS
  Identical data, analyzed using different criteria, led to almost three-fold difference (2.8-8.3%) in diagnostic rate. This increase is mostly explained by increasing the cut-off values of VWF measurements from < 30 to ≈ 40 IU dL(-1) . Further refinement of the laboratory diagnosis of type 1 VWD is a priority.
authors.affiliation: Department of Clinical Laboratory, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: T
authors.initials: T
authors.lastname: Quiroga
authors.forename: M
authors.initials: M
authors.lastname: Goycoolea
authors.forename: S
authors.initials: S
authors.lastname: Belmont
authors.forename: O
authors.initials: O
authors.lastname: Panes
authors.forename: E
authors.initials: E
authors.lastname: Aranda
authors.forename: P
authors.initials: P
authors.lastname: Zúñiga
authors.forename: J
authors.initials: J
authors.lastname: Pereira
authors.forename: D
authors.initials: D
authors.lastname: Mezzano
mesh_terms: D001324:Autoantigens / Q000097:blood; D019411:Clinical Laboratory Techniques; D006801:Humans; D012189:Retrospective Studies; D056725:von Willebrand Disease, Type 1 / Q000097:blood / Q000175:diagnosis*
chemical_list: D001324:Autoantigens
keywords: blood coagulation disorders, inherited; diagnosis; hematologic tests; von Willebrand disease, type 1; von Willebrand factor