Background: A majority of patients with a mild to moderate bleeding tendency (mild bleeding disorders, MBD) remains without a diagnosis, despite extensive laboratory investigations (bleeding of unknown cause, BUC). Patients with BUC do not differ in their bleeding phenotype to patients with an established MBD like von Willebrand disease (VWD) or platelet function defects (PFD). Whole-blood thromboelastometry (ROTEM) depicts diverse aspects of coagulation including hyper-fibrinolysis and captures the influence of erythrocytes, leucocytes and platelets to hemostasis, which might contribute to BUC. Aims: To analyze clinical risk factors for ROTEM parameters and compare results between patients with BUC and an established MBD. Methods: Patients from the Vienna bleeding biobank (VIBB, EC no. 603/2009) were analyzed (Gebhart et al, Haemophilia, 2018). Viscoelastic clot measurement was performed with non-activated ROTEM® (EM International, Munich, Germany): clotting time (CT, sec, time from analysis start until start of clot formation), clot formation time (CFT, sec, time needed to form a clot), maximum clot firmness (MCF, mm, peak amplitude of the clot) and maximal lysis (ML, %, expression of clot lysis in % of MCF). Results: ROTEM was performed in 513/714 (71.8%) patients included in the VIBB. The mean(SD) age was 41.4 (15.0) years, 425 (80.3%) were women and 252 (47.6%) patients had blood group O. In total, 318 patients had BUC, the reaiming patients hat PFD(n=122, 23.7%), VWD (n=51, 9.9%), mild clotting factor deficiencies (CFD, n=18, 3.5%) and 4 had an other bleeding disorder (0.8%). Clinical factors that were independently associated with ROTEM values in BUC patients were sex, blood group O (vs. non-O) and the bleeding score (multivariable linear regression, Table 1). BUC patients had comparable ROTEM results as patients with platelet function defects or VWD, after adjusting for blood group O and sex, whereas patients with clotting factor deficiency had longer CT and CFT, a lower MCF and higher ML (Table 2). Image:Summary/Conclusion: Hemostatic capacity measured by ROTEM is similar in patients with BUC and those with mild primary hemostatic bleeding disorders. Our data support the hemostatic imbalance in patients with BUC.