Association of age with the ISTH-BAT score and prevalence of bleeding symptoms in patients with bleeding disorder of unknown cause: results from the Vienna bleeding biobank

Introduction Bleeding disorder of unknown cause (BDUC) is a diagnosis of exclusion defined only by a clinically relevant bleeding phenotype in the absence of identifiable laboratory abnormalities. The International Society on Thrombosis and Haemostasis bleeding assessment tool (ISTH-BAT) is widely used to quantify bleeding severity. Recent studies in healthy individuals indicate that ISTH-BAT scores increase with age, particularly among women, but this association has not been comprehensively evaluated in patients with BDUC. Method We analyzed the association between age and ISTH-BAT in patients with BDUC at study inclusion in the Vienna Bleeding Biobank (VIBB), a single-center observational cohort study. Patients were categorized into four age groups based on quartiles (Q) of age at study inclusion: Q1 (16–28 years), Q2 (29–37 years), Q3 (38–51 years), and Q4 (≥52 years). Results Of 1,007 patients with mild to moderate bleeding disorders enrolled in the VIBB, 635 (63.1%) were classified as having BDUC. The proportion of female patients was highest in the third age quartile (Q3), whereas blood group O was most prevalent in the oldest quartile (Q4). With the exception of a higher prevalence of hypertension, diabetes, and osteoporosis ([ Fig. 1 ]), other comorbidities did not differ significantly across age groups (not shown). Several hemostatic parameters, including platelet count, fibrinogen, VWF:Ag, VWF activity, and FVIII activity, increased with age ([ Fig. 1 ]). Fig. 1 Clinical and laboratory characteristics of BDUC patients according to their age group Spearman correlation analysis revealed no clear association between age and ISTH-BAT or the number of bleeding symptoms ([ Fig. 2A,B ]), reported at study inclusion. However, ISTH-BAT scores differed significantly among age quartiles ([ Figure 2C ]), with the highest median scores observed in Q3. The prevalence of abnormal ISTH-BAT scores (≥4 for men and≥6 for women) was also greatest in Q3, both in women and men ([ Figure 2D,E ]), but male patients in Q4 showed the lowest prevalence ([ Figure 2E ]). When applying age-adjusted cutoffs for women, as proposed by Doherty et al. ( J Thromb Haemost 2023), this age-related increase was no longer observed ([ Figure 2F ]). Fig. 2 Association of age with ISTH-BAT score and bleeding symptoms in BDUC patients. A: Spearman correlation between age and ISTH-BAT score; B Spearman correlation between age and number of bleeding manifestations; C: ISTH-BAT score across age groups (quartile 1-4); D: Abnormal (pathological) ISTH-BAT score across age groups; E: Abnormal (pathological) ISTH-BAT score across age groups and according to sex; F: Abnormal ISTH-BAT scores according to sex-specific cutoffs in different age groups and according to sex; G: Prevalence of bleeding symptoms at study inclusion according to age groups Younger patients most frequently reported easy bruising and oral mucosal bleeding at study inclusion, whereas surgery-related bleeding complications accumulated in older individuals ([ Fig. 2G ]). Among women, heavy menstrual bleeding was most frequently reported in Q3, while postpartum hemorrhage was least frequently reported in Q1. Statistically significant differences between age groups were also observed for gastrointestinal and central nervous system bleeding. Conclusion ISTH-BAT scores and bleeding symptoms show an age-dependent pattern in BDUC, mainly driven by female-specific and surgery-related bleeding. Age substantially influences the bleeding phenotype and diagnostic classification, supporting the use of age-adjusted ISTH-BAT cutoffs in women alongside clinical judgment. Publication History Article published online: 17 February 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany