Predictors for future bleeding in bleeding disorder of unknown cause

Bleeding disorder of unknown cause (BDUC) is increasingly recognized as a common diagnosis among adult patients with mild to moderate bleeding symptoms and is reflective of unremarkable hemostatic tests despite a clinically relevant bleeding tendency. While extensive clinical and basic research has been conducted on the bleeding phenotype and underlying mechanisms of BDUC, great uncertainty remains regarding the long-term risk for spontaneous bleeding and the bleeding risk after hemostatic challenges. Currently available data suggest that a substantial portion of BDUC patients continue to experience spontaneous bleeding symptoms, such as easy bruising, epistaxis, and heavy menstrual bleeding. Risk factors associated with the persistence of these symptoms include the presence of the respective symptom prior to the BDUC diagnosis and a higher baseline bleeding score. Furthermore, a large proportion of BDUC patients report bleeding complications after surgery or child delivery prior to initial investigations. Patients with prior bleeding complications after such events, patients with blood group O, and patients who did not receive hemostatic prophylaxis demonstrate an increased risk for postinterventional bleeding during follow-up. Although BDUC remains a diagnosis of exclusion, accumulating data underscore the need to recognize it as a potentially persistent clinically relevant condition. Future studies should focus on refining diagnostic algorithms, investigating underlying mechanisms, and developing predictive tools for bleeding risk to improve individualized management strategies.