Effect of age on ISTH-BAT scores and Low VWF diagnosis in the Zimmerman Program Open Access

• Age critically influences ISTH-BAT scores and thus formal Low VWF / type 1 VWD diagnosis in patients with VWF levels 30-50 IU/dL.

• In children with VWF levels 30-50 IU/dL, age and sex impact ISTH-BAT scores and utility for Low VWF / type 1 VWD diagnosis.

An essential component of Low VWF / type 1 VWD diagnosis is to identify patients with an increased bleeding phenotype, as most individuals with VWF levels in the 30-50 IU/dL range do not bleed. The ISTH-BAT, a widely used tool for assessing bleeding severity, has recently been shown to be age-dependent. While age may also influence ISTH-BAT scores in individuals with VWF levels between 30-50 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, while 105 (32.3%) had normal scores. Our analysis demonstrates that age critically influences the likelihood of attaining an abnormal ISTH-BAT score and thus being registered with a formal diagnosis of Low VWF /type 1 VWD. For example, if children are first assessed at ³ 10 years, they are twice as likely to have an abnormal ISTH-BAT compared to those first investigated < 10 years (p<0.001). Additionally, the prevalence of abnormal ISTH-BAT scores was significantly higher in women aged ≥44 years (91.8%) compared to women aged 18-28 years (66.7%; p=0.004). Finally, we demonstrate that the change in abnormal ISTH-BAT threshold at the age of 18 critically impacts Low VWF diagnosis, due to lower rates of abnormal ISTH-BAT scores in young adults (p=0.006). 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.