tPA-ROTEM identifies hyperfibrinolytic profile in a significant proportion of patients with bleeding disorder 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). Little is known about the role of the fibrinolytic pathway in BDUC patients. Aim: 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: Patients with an increased bleeding tendency were included in a prospective cohort study. BDUC patients were identified based on an increased bleeding tendency and no abnormalities in extensive laboratory testing. The tPA-ROTEM assay was performed and plasma levels of PAI-1 activity and antigen, a2-antiplasmin, tPA antigen and TAFI were measured using ELISA assays. Pre-specified definitions of hyper- and hypofibrinolysis were applied. Results: tPA-ROTEM identified a hyperfibrinolytic profile in 19/92 (21 %) of BDUC patients. Multivariable regression analysis showed that lower PAI-1 antigen levels were independently associated with hyperfibrinolysis. Conclusion: tPA-ROTEM identified a hyperfibrinolytic profile in 21 % of BDUC patients. These findings suggest that antifibrinolytic medications may be useful to control bleeding or prevent bleeding in surgical interventions in a group of patients with BDUC.