PB0188 - Fibrinolysis assessment with tPA-ROTEM in patients with Bleeding Disorders of Unknown Cause (BDUC)

Background: In the majority of patients referred for evaluation of bleeding symptoms, no diagnosis can be made after extensive laboratory testing. These patients are classified as having a bleeding disorder of unknown cause (BDUC). Several hemostasis assays have been investigated in BDUC-patients, but little is known about the role of the fibrinolytic pathway. The lack of standardized fibrinolysis tests and their limited availability could explain this.

Aims: We aimed to investigate the capacity of the tPA-ROTEM assay to detect fibrinolytic abnormalities in BDUC-patients and to correlate these findings with fibrinolytic protein activity levels.

Methods: Data from patients referred to the hematologist for bleeding evaluation were used. BDUC-patients were identified based on an increased bleeding tendency and no abnormalities in extensive laboratory testing. tPA-ROTEM assay was done according to the in 2016 validated and published method. Fibrinolysis protein plasma levels were measured using ELISA assays. Pre-specified definitions of hyper- and hypofibrinolysis were applied.

Results: tPA-ROTEM identified a hyperfibrinolytic profile in 15/73 (20%) of BDUC-patients, a hypofibrinolytic profile in 16/73 (22%) of BDUC-patients and a normal profile in 42 BDUC-patients (58%). Plasminogen activity inhibitor 1 (PAI-1) activity and antigen levels and α2-antiplasmin levels were lower in BDUC-patients with hyperfibrinolysis compared to BDUC-patients with hypofibrinolysis. No statistically significant correlations between tPA-ROTEM parameters and fibrinolysis protein plasma levels were identified using multivariate regression analysis.

Conclusion(s): tPA-ROTEM identified a hyperfibrinolytic profile in 20% of BDUC-patients. In this group, the lower PAI-1 activity and antigen levels and lower α2-antiplasmin levels are in concordance with the expected changes in case of hyperfibrinolysis. These findings indicate that these fibrinolysis protein plasma levels are within the lower functional range of their distribution, shifting the balance towards increased clot lysis leading to an increased bleeding tendency. These findings might deliver evidence to the use of antifibrinolytic therapies in BDUC-patients in case of bleeding or interventions.