High Prevalence of Bleeding Disorder of Unknown Cause in Women: findings from the Maastricht Bleeding Cohort
Mild bleeding disorders (MBDs) include von Willebrand disease (VWD), platelet function disorders (PFD), mild clotting factor deficiencies, and fibrinolytic abnormalities. In contrast, Bleeding Disorders of Unknown Cause (BDUC) refer to patients with a bleeding phenotype in whom no specific hemostatic defect can be identified despite extensive laboratory investigation. Diagnosing MBD's is challenging due to overlapping phenotypes, leading to lengthy and costly procedures, particularly for BDUC (Heubel et al. 2023). The aim of this study is to investigate patient and laboratory characteristics and patterns according to final diagnosis in a large cohort of patients referred for bleeding evaluation to the Maastricht University Medical Center (MUMC+).
Since 2016, all patients referred for bleeding evaluation at MUMC+ were invited to participate in the Predictors of Bleeding Evaluation in Adult Hematologic Patients (ProBe-AHP) study. All underwent International Society on Thrombosis and Haemostasis - Bleeding Assessment Tool (ISTH-BAT) scoring and extensive laboratory haemostasis testing.
359 patients were included, 83% was female, the median age was 42 (IQR 31-59), 20.1% were diagnosed with no bleeding disorder (NBD), 35.4% with a MBD (59.1% PFD, 12.6% VWD, 7.9% clotting factor deficiency), and 44.6% with BDUC. ISTH-BAT scores were highest in BDUC patients with a score of 8 (IQR 6-10), compared to a score of 7 in MBD (IQR 3-10) while NBD patients scored lowest with a score of 3 (IQR 2-4). Heavy menstrual bleeding (HMB) was reported more frequently in BDUC compared to MBD (77.2% vs. 50.0%; p<0.001). In addition, postpartum bleeding (PPH) was more common in BDUC than in MBD (39.2% vs. 26.0%; p=0.049). Together with prolonged bleeding of minor wounds, spontaneous gum bleeding and post-surgical bleeding, HMB and PPH were identified as predictive factors for BDUC diagnosis. Male gender, post-dental extraction bleeding and a diagnosed bleeding disorder in family history were predictive for MBD diagnosis. In general, women were more likely to receive the diagnosis BDUC compared to men (OR 4.7; 2.3-9.3 95% CI). Women who reported HMB were more likely to receive the diagnosis BDUC, compared to a MBD (OR 2.2; 1.2-4.2 95% CI).
Women were more frequently diagnosed with BDUC, particularly in the presence of gender-specific symptoms such as heavy menstrual and postpartum bleeding. In contrast, male gender and a positive family history were more indicative of MBD. These findings suggest that gender- and symptom-specific patterns may play a role in the diagnostic distinction between BDUC and MBD.