Rare Bleeding Disorders and Bleeding Disorder of Unknown Cause: Current Understanding and Recent Developments

Rare bleeding disorders (RBDs) represent a diverse group of inherited conditions involving coagulation factors or platelets. These conditions, such as Glanzmann thrombasthenia (GT) or severe coagulation factor deficiencies, are uncommon. In contrast, bleeding disorder of unknown cause (BDUC) is a diagnosis of exclusion without an identifiable genetic defect and has emerged as the most frequent finding in patients evaluated for a lifelong bleeding tendency. Their clinical presentation is highly variable and often not well predicted by standard laboratory findings. This State-of-the-Art review summarizes current understanding and recent developments across four representative conditions: inherited platelet function disorders (IPFDs) highlighting GT, fibrinogen disorders, factor XI (FXI) deficiency, and BDUC. In IPFDs, management remains challenging because of wide variability in bleeding severity and the need for specialized expertise. In fibrinogen disorders, the limited assay availability hampers consistent classification and management. FXI deficiency illustrates the weak association between factor levels and bleeding phenotype, underlining the importance of individualized care. Finally, studies on BDUC reveal overlaps with mild inherited disorders and highlight the value of global haemostatic and fibrinolytic assays in improving diagnostic precision. Across these four disorders, common priorities emerge, such as harmonizing diagnostic approaches, strengthening international registries, and integrating patient-reported outcomes to better capture real-life impact.