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1252 Fibrinolysis Assessment with Tpa-ROTEM in Patients with Bleeding Disorders of Unknown Cause (BDUC)

Program: Oral and Poster Abstracts
Session: 322. Disorders of Coagulation or Fibrinolysis: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
adult, Research, Bleeding and Clotting, bleeding disorders, Translational Research, assays, Diseases, Technology and Procedures, Study Population, Human
Saturday, December 9, 2023, 5:30 PM-7:30 PM

Amaury Monard, MD1,2*, Yvonne Henskens3,4*, Paul Verhezen5*, Dave Hellenbrand6*, Erik AM Beckers, MD, PhD7 and Floor Moenen8*

1Department of internal medicine, Maastricht University, Maastricht, AL, Belgium
2Carim- school for cardiovascular diseases, Maastricht, Netherlands
3Maastricht UMC+, Maastricht, NLD
4CARIM - School for cardiovascular disease, Maastricht, Netherlands
5Maastricht University Medical Center, Central Diagnostic Laboratory, Unit For He, Maastricht, NLD
6Central Diagnostic Laboratory, Maastricht University Medical Center + (MUMC+), Maastricht, Netherlands
7Maastricht University Medical Center, Maastricht, NLD
8Department of Hematology, Maastricht University Medical Center, Maastricht and Hemophilia Treatment Center Nijmegen-Eindhoven-Maastricht, Maastricht, Netherlands


In 40-70% of patients referred to the hematologist for evaluation of bleeding symptoms, no cause for their increased bleeding tendency can be found using currently available hemostasis laboratory tests. This group is classified as patients with bleeding disorder of unknown cause (BDUC). The lack of clear guidelines concerning diagnosis, management and genetic counseling in BDUC-patients poses a challenge for patients, family members and treating physicians. Several hemostasis assays have been investigated in BDUC-patients, but little is known about the role of the fibrinolytic pathway in this patient group. This can be explained by the lack of standardized fibrinolysis tests and the limited availability of these tests in laboratories. To further unravel potential bleeding mechanisms in BDUC, in the present study we assessed fibrinolysis in BDUC patients by using a global whole blood tPA ROTEM assay and determining of individual fibrinolysis proteins.


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 in plasma.


Data from patients referred to the hematologist for bleeding evaluation and included in the Prediction of Evaluation in Adult Hematologic Patients with Bleeding Tendencies (ProBe-AHP) study (METC:14-4-036) were used. BDUC-patients were identified based on (1) a clinically relevant increased bleeding tendency and (2) no abnormalities in extended hemostasis laboratory testing. tPA-ROTEM assay was done according to the in 2016 validated and published method on the ROTEM device. Fibrinolysis protein plasma levels, including plasminogen, plasminogen activator inhibitor 1 (PAI-1) antigen and activity, tissue plasminogen activator (tPA) antigen, alpha2-antiplasmin and thrombin activatable fibrinolysis inhibitor (TAFI), were measured using ELISA assays. Pre-specified definitions of hyper- and hypofibrinolysis as measured by tPA-ROTEM were applied to identify hyper- and hypofibrinolytic profiles.


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 a hyperfibrinolytic profile compared to BDUC-patients with a hypofibrinolytic profile. No statistically significant correlations between tPA-ROTEM parameters and fibrinolysis protein plasma levels were identified using multivariate regression analysis.


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.

Informed consent and approval from the medical-ethical committee from Maastricht (METC azM/UM) were obtained.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH