This paper reports on the use of a high-throughput diagnostic genetic screening for coagulation, platelet, or thrombotic disorders in a series of more than 2000 patients.

Key Points: New onset of thrombosis is an independent risk factor for increased mortality in LA-positive individuals. Life expectancy in our cohort of patients with LA was worse in comparison with an Austrian reference population.

Background In a large proportion of patients with a mild‐to‐moderate bleeding tendency no diagnosis can be established (bleeding of unknown cause, BUC). Objectives To investigate possible dysfunctions in thrombin generation (TG) and plasma clot formation and lysis in patients with BUC from the Vienna Bleeding Biobank (VIBB). Patients and Methods: Thrombin generation and plasma clot properties of 382 BUC patients were compared to those of 100 healthy controls and 16 patients with FVIII activity ≤50%. Results Thrombin generation was significantly impaired in BUC patients compared to healthy controls, exhibiting a prolonged lag‐time and time‐to‐peak (TTP), and decreased maximum thrombin generation, velocity index (VI), and area under the curve (AUC). The assessment of clot formation and lysis in BUC patients revealed a lower clot formation rate (Vmax), resulting in a longer TTP, increased absorbance (ΔAbs) and a shorter clot lysis time (CLT) than in healthy controls. Comparing patients with FVIII activity ≤50% to those with BUC, parameters of thrombin generation and clot formation and lysis were either stronger or comparably impaired. Bleeding severity did not correlate with parameters of thrombin generation, clot formation or clot lysis. Conclusion Patients with BUC have an impaired hemostatic capacity reflected by a lower thrombin generation potential, a lower clot formation rate, increased clot turbidity and shorter clot lysis time, which might contribute to their increased bleeding tendency. Assays monitoring these parameters can alert physicians of haemostatic impairment and should be considered in situations where traditional hemostatic lab tests fail to reveal the clinical bleeding tendency.

Blood group O has been associated with an increased bleeding tendency due to lower von Willebrand factor (VWF) and factor VIII (FVIII) levels. We explored whether blood group O is independently associated with bleeding severity in patients with mild-to-moderate bleeding of unknown cause (BUC) in the Vienna Bleeding Biobank cohort. Bleeding severity was recorded with the Vicenza bleeding score (BS). Blood group O was overrepresented in 422 patients with BUC compared with its presence in 23 145 healthy blood donors (47.2% vs 37.6%; odds ratio, 1.48; 95% confidence interval [CI], 1.22-1.79). The BS and the number of bleeding symptoms were significantly higher in patients with blood group O than in patients with non-O after adjustment for VWF and FVIII levels and sex (least-square [LS] means of BSs: 6.2; 95% CI, 5.8-6.6 vs 5.3; 4.9-5.7; and of number of symptoms: LS, 3.5; 95% CI, 3.2-3.7 vs 3.0; 2.8-3.2, respectively). Oral mucosal bleeding was more frequent in those with blood group O than in those with other blood types (group non-O; 26.1% vs 14.3%), independent of sex and VWF and FVIII levels, whereas other bleeding symptoms did not differ. Patients with blood group O had increased clot density in comparison with those with blood group non-O, as determined by rotational thromboelastometry and turbidimetric measurement of plasma clot formation. There were no differences in thrombin generation, clot lysis, or platelet function. Our data indicate that blood group O is a risk factor for increased bleeding and bleeding severity in patients with BUC, independent of VWF and FVIII levels.