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1218 Discriminating Factors of Bleeding Disorder of Unknown Cause in a Cohort of Patients with Mild to Moderate Bleeding Disorders

Program: Oral and Poster Abstracts
Session: 323. Disorders of Coagulation, Bleeding, or Fibrinolysis, Excluding Congenital Hemophilias: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Adult, Research, Clinical Practice (Health Services and Quality), Clinical Research, Human, Study Population
Saturday, December 7, 2024, 5:30 PM-7:30 PM

Tim Dreier*, Dino Mehic, MD*, Justin Oosterlee, MD*, Jasmin Sabrina Rast, MD*, Cihan Ay*, Ingrid Pabinger, MD and Johanna Gebhart, MD*

Department of Medicine I, Clinical Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria

Background. Distinguishing a bleeding disorder of unknown cause (BDUC) from established mild to moderate bleeding disorder (MBD) diagnoses, such as platelet function defects (PFD), von Willebrand disease (VWD) and coagulation factor deficiencies (CFD), has proven challenging due to similar bleeding phenotypes, bleeding severity and cohort characteristics. Hence, the exclusion of established MBD diagnoses and the diagnosis of a BDUC currently requires an extensive and lengthy hemostatic investigation. Identification of discriminating factors of BDUC could therefore streamline the diagnostic process and ultimately reduce the burden on patients.

Aims. In this study, we aimed to investigate MBD patient characteristics associated with established MBD diagnoses or BDUC. Additionally, current diagnostic tools, such as the ISTH-Bleeding Assessment Tool (ISTH-BAT) and its cutoff, were evaluated for their efficacy to distinguish between established MBD diagnoses and BDUC.

Methods. Adult patients from the Vienna Bleeding Biobank (VIBB), an ongoing prospective single-center cohort study on MBD patients, were analyzed. Overall study design, in- and exclusion criteria of the VIBB and diagnostic criteria for established MBD diagnoses and BDUC have been published previously. (Mehic et.al., Haemostaseologie, 2024) At study inclusion, the ISTH-BAT was recorded in a detailed interview by trained professionals and an extensive hemostatic investigation was conducted, including repeated global hemostatic tests, coagulation factor measurements and platelet function analyses.

P-values were corrected for multiple testing using the Bonferroni-Holm-Correction.

Results. 882 MBD patients were analyzed, of which 557 (63%) were classified as BDUC patients. Of the remaining 325 patients, 235 (27%) had PFD, 72 (8%) were diagnosed with VWD and 20 (2%) had CFD. Overall, 84% of MBD patients (n=743) were female, with a mean age of 41 years. Furthermore, 49% of MBD patients had blood group O (BGO), and 35% had a positive family history of bleeding tendencies. BDUC was significantly more common among women (X²-test, p=0.013) and with higher age (t-test, p=0.003), while BGO was more common in patients with established MBD diagnoses (vs. non-BGO, X²-test, p=0.031). Family history of bleeding was similar in both groups. In multivariate regression, female sex and higher age were significantly associated with BDUC (odds ratio [OR]: 1.64, 95% confidence interval [CI]: 1.12-2.39, OR: 1.02 [1.01-1.02], respectively), with BGO prevailing as associated with established MBD diagnoses (OR: 1.46 [1.09-1.54]). Family history of bleeding remained non-significant.

The median ISTH-BAT score in the total study cohort was 6 (interquartile range [IQR]: 4-8), and there was no significant difference between BDUC patients and those diagnosed with an established MBD diagnosis (5 [4-8] vs. 6 [4-9]; p=0.491). However, patients with established MBD diagnoses who had experienced post-partal bleeding complications prior to inclusion required invasive emergency treatment (in 79%) significantly more often than BDUC patients with 51% (X2-test, p=0.005), leading to an overall higher score in this symptom (Wilcoxon rank-sum test p=0.007). There was no difference in the severity of other symptoms.

Applying the recently published revised sex- and age-dependent cutoff of the ISTH-BAT (Doherty et. al., J Thromb Haemost, 2023), 498 MBD patients (56%) had an above-cutoff ISTH-BAT score. Of BDUC patients, 310 patients (56%) were above the cutoff, which was similar to patients with an established MBD diagnosis (n=187, 57%), resulting in a non-significant difference (X2-test, p=0.636).

Conclusions. When comparing BDUC with established MBD diagnoses, we have identified an overrepresentation of women and a higher mean age in the subgroup of BDUC patients, while BGO was associated with an established MBD diagnosis. The overall ISTH-BAT score was similar in BDUC and established MBD diagnosis patients. However, patients with an established MBD diagnosis required invasive interventions to treat post-partal bleeding more often.

Ultimately, patients with BDUC present similar to patients with an established MBD diagnosis. While associations between certain patient characteristics, laboratory markers and symptoms can be observed, early triage of MBD patients into fast-track and extensive diagnostic groups is currently not feasible.

Disclosures: Mehic: CSL Behring: Honoraria, Other: advisory board meetings . Ay: BMS, Pfizer, Daiichi-Sankyo, Bayer, Sanofi, Novo Nordisk, CSL Behring, Sobi, Roche: Honoraria, Speakers Bureau. Pabinger: CSL Behring, Sobi, Rovi, Takeda, Pfizer: Consultancy, Honoraria; CSL Behring, Sobi: Other: Advisory Board Meetings. Gebhart: CSL Behring, Novartis, Amgen, Sobi: Honoraria, Other: advisory board meetings, Research Funding.

*signifies non-member of ASH