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.

The high rate of patients with BUC despite in-depth haemostatic assessment underlines the incompleteness of available routine laboratory tests. Males with MBDs were more likely to be diagnosed with an established bleeding disorder than females.

• 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. Concomitant autoimmune diseases, anticoagulant treatment at baseline, or positivity for anticardiolipin-or anti-b2-glycoprotein I antibodies were not associated with mortality. In a relative survival analysis, our cohort of LA positives showed a persistently worse survival in comparison with an age-, sex-, and study-inclusion-year-matched Austrian reference population. The cumulative relative survival was 95.0% (95% CI, 88.5-98.8) after 5 years and 87.7% (95% CI, 76.3-95.6) after 10 years. We conclude that occurrence of a thrombotic event is associated with higher mortality in patients with LA. Consequently, the prevention of thromboembolic events in LA positives might improve survival. (Blood. 2015;125(22):3477-3483)

BackgroundIn a large proportion of patients with a mild to moderate bleeding tendency no diagnosis can be established (bleeding of unknown cause, BUC).ObjectivesTo investigate possible dysfunctions in thrombin generation and plasma clot formation and lysis in patients with BUC from the Vienna Bleeding Biobank (VIBB).Patients and MethodsThrombin generation and plasma clot properties of 382 BUC patients were compared to those of 100 healthy controls and 16 patients with factor VIII (FVIII) activity ≤50%.ResultsThrombin generation was significantly impaired in BUC patients compared to healthy controls, exhibiting a prolonged lag time and time to peak and decreased maximum thrombin generation, velocity index, 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.ConclusionPatients 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 hemostatic impairment and should be considered in situations where traditional hemostatic lab tests fail to reveal the clinical bleeding tendency.

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