Abstract

Introduction: 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. Aim: 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. Discussion: 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 approximate to 40 IU dL(-1). Further refinement of the laboratory diagnosis of type 1 VWD is a priority.