High Prevalence and Clinical Burden of Bleeding Disorder of Unknown Cause in Adolescents With Heavy Menstrual Bleeding: Application of New Definition by the International Society on Thrombosis and Haemostasis

Abstract

BACKGROUND: Bleeding disorder of unknown cause (BDUC) is increasingly recognized in patients with clinically significant bleeding despite normal haemostatic testing. The International Society on Thrombosis and Haemostasis (ISTH) recently proposed a standardized definition incorporating bleeding phenotype and validated assessment tools. OBJECTIVE: To determine the prevalence and clinical impact of BDUC in adolescents with heavy menstrual bleeding (HMB) using the ISTH definition for BDUC. RESULTS: Among 205 adolescents, 57.6% met criteria for BDUC, including 86.8% of those without an established bleeding disorder using the ISTH paediatric bleeding assessment tool threshold ≥3, most with clinically significant HMB (PBAC >100). Adolescents with BDUC demonstrated similar bleeding severity, with comparable ISTH-BAT and PBAC scores (p = 0.95 and p = 0.62, respectively) as those with diagnosed bleeding disorders. However, BDUC was associated with higher rates of anaemia (50% vs. 31%, p = 0.016) and increased emergency department utilization (47% vs. 30%, p = 0.03), while iron deficiency, hospitalizations, and transfusion requirements were similar between groups. Health-related quality of life was similarly impaired in both groups (PedsQL fatigue scores of 61.1 vs. 59.6, p = 0.65). CONCLUSION: BDUC is highly prevalent among adolescents with HMB and is associated with a clinical burden comparable to, and in some domains exceeding, that of established bleeding disorders. These findings support BDUC as a clinically meaningful phenotype and highlight the need for improved diagnostic precision and targeted management strategies.