The majority of pediatric patients with von Willebrand disease (VWD) have diagnostic laboratory values the first time they undergo laboratory testing for the disease, according to results from a retrospective single-center study published in the Journal of Thrombosis and Haemostasis. These results suggest that pediatric patients with no family history of the disease and with testing results that do not indicate disease might not need to undergo additional testing to exclude a diagnosis of VWD.
Accurate diagnosis of VWD in pediatric patients is complex because of the variability within and across assays that measure von Willebrand factor (VWF), the absence of a significant bleeding history to associate with laboratory results, and stress-induced increases in levels of VWF. In patients with no clear family history of VWD and with ambiguous assay results, guidelines recommend repeat assays, though the validity of these guidelines had not been assessed in pediatric patients.
In this single-center study at the Children’s Hospital of Philadelphia in Pennsylvania, researchers assessed 811 patients between 0 and 18 years of age who had been evaluated for a suspected bleeding disorder between January 2012 and July 2017. Of these identified patients, 22.2% were diagnosed with VWD. Approximately 70% of patients diagnosed with VWD received their diagnosis following the initial laboratory test.
The most common reasons clinicians chose laboratory testing for possible VWD were epistaxis, menorrhagia, cutaneous bleeding, abnormal coagulation test results, and family history of the disease. The odds of being diagnosed with VWD were only significantly higher in patients referred for abnormal coagulation tests (odds ratio [OR], 1.61; 95% CI, 1.07-2.24) and family history of VWD (OR, 1.78; 95% CI, 1.23-2.54).
Compared with patients without VWD, patients with the disease were more likely to have family members with VWD (38% vs. 22%; P <.001) and were younger (5.8 vs. 8.5 years; P =.002).
Univariate analysis did not reveal any clinical factors associated with a requirement for multiple tests for a diagnosis of VWD. The authors explained, “Unfortunately, for the minority of patients diagnosed with repeat testing, no clinical factors were identified to aid clinicians in decision making.”
Researchers used a cutoff of 100 IU/dL for VWF antigen to evaluate the laboratory level above which additional testing did not inform potential diagnosis. At 100 IU/dL for VWF antigen, sensitivity was 95%, specificity was 38%, and negative predictive value was 96.6%. When the same cutoff of 100 IU/dL was applied for VWF activity, the sensitivity was 98%, the specificity was 38%, and the negative predictive value was 98.6%.
Results from this study indicate that initial laboratory testing correctly identifies the large majority of pediatric patients with VWD, though no clinical factors associated with a need for additional testing to make a diagnosis were identified.
1. Doshi BS, Rogers RS, Whitworth HB, et al. Utility of repeat testing in the evaluation for von Willebrand disease in pediatric patients [published online July 26, 2019]. J Thromb Haemost. doi:10.1111/jth.14591