Effect of age on ISTH-BAT scores and low VWF diagnosis in the Zimmerman Program

An essential component of low von Willebrand factor (VWF)/type 1 von Willebrand disease (VWD) diagnosis is to identify patients with an increased bleeding phenotype, as most individuals with VWF levels in the 30 to 50 IU/dL range do not bleed. The International Society on Thrombosis and Haemostasis-bleeding assessment tool (ISTH-BAT), widely used for assessing bleeding severity, has recently been shown to be age dependent. Although age may also influence ISTH-BAT scores in individuals with VWF levels between 30 and 50 IU/dL, and subsequently affect low VWF diagnosis, this relationship has not been investigated. Therefore, we analyzed 325 participants from the Zimmerman Program, of whom 220 (67.7%) had abnormal ISTH-BAT scores, whereas 105 (32.3%) had normal scores. Our analysis demonstrates that age critically influences the likelihood of attaining an abnormal ISTH-BAT score and, consequently, being registered with a formal diagnosis of low VWF/type 1 VWD. For example, children first assessed at ≥10 years, are twice as likely to have an abnormal ISTH-BAT compared with those first investigated at <10 years (P < .001). In addition, the prevalence of abnormal ISTH-BAT scores was significantly higher in women aged ≥44 years (91.8%) compared with women aged 18 to 28 years (66.7%; P = .004). Finally, we demonstrate that the change in abnormal ISTH-BAT threshold at the age of 18 years critically affects low VWF diagnosis, owing to lower rates of abnormal scores in young adults (P = .006). In conclusion, we demonstrate that the likelihood of a low VWF/type 1 VWD diagnosis is influenced by the age at which ISTH-BAT is first assessed in individuals with mild-to-moderately reduced VWF levels.