PB1206 - Plasmin generation is impaired in patients with bleeding disorders of unknown cause

Tuesday, June 27, 2023

18:30 – 19:30 ET

Room: Exhibition

Presenting Author(s)

Dino Mehic, MD

Resident physician
Clinical Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria
Vienna, Wien, Austria

Co-Author(s)

Stéphanie E. Reitsma, PhD

Postdoc
Department of Pathology and Laboratory Medicine, UNC Blood Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Chapel Hill, North Carolina, United States
HH

Helmuth Haslacher

Senior Consultant
Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
Vienna, Wien, Austria
MK

Maximilian Köller

PhD student
Department of Pathology, Medical University of Vienna, Vienna, Austria
Vienna, Wien, Austria
Bd

Bas de Laat, MD, PhD

General Director
Department of Functional Coagulation, Synapse Research Institute, Maastricht, the Netherlands
Maastricht, Limburg, Netherlands
Cihan Ay, MD (he/him/his)

Professor, Head of the Thrombosis and Haemostasis Research Group
Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria
Vienna, Wien, Austria
Ingrid Pabinger, MD

Co-Head of the Thrombosis and Haemostasis Research Group
Clinical Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria
Vienna, Wien, Austria
Alisa S. Wolberg, PhD

Professor
Univerisity of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States
Johanna Gebhart, MD, PhD (she/her/hers)

Ap. Prof. Dr. PhD
Clinical Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria
Vienna, Wien, Austria

Background: In most patients with mild bleeding disorders (MBD) no diagnosis can be established despite extensive investigations of plasmatic coagulation and platelet function. Evidence of hemostatic imbalance has been detected in bleeding disorders of unknown cause (BDUC), but the role of fibrinolytic alterations remains inconclusive.

Aims: To investigate the fibrinolytic capacity by measuring plasmin generation (PG) potential in plasma from BDUC patients.

Methods: PG parameters from 376 citrated plasmas from the Vienna bleeding biobank (VIBB, EC 603/2009), a prospective cohort-study on MBD, and 100 healthy controls (HC) were analyzed using calibrated fluorescence detection. The end of the PG curve (start tail, ST) was set to 60 minutes or sooner, as needed to calculate PG parameters.

Results: Subject characteristics and PG parameters are shown in Table 1. Higher fibrinogen in BDUC patients compared to HC moderately correlated with plasmin peak (r=0.44, p< 0.001), but not with other PG parameters.
BDUC patients had a longer time to peak (TTP) and ST, and lower velocity and plasmin peak, but higher endogenous plasmin potential (EPP). Except for TTP, these differences persisted after adjusting for fibrinogen levels. PG did not correlate with clinical parameters including bleeding scores, age, blood group (O vs. non-O) or sex (data not shown).
Multivariate logistic analysis using diagnosis of BDUC or HC as a binomial outcome revealed that plasmin peak, EPP, ST, and fibrinogen independently (all with p< 0.001) predict BDUC. A model combining peak, EPP and ST with fibrinogen yielded area under the receiver curves of 0.819 and 0.866 for model validation (A) and training (B), respectively (Figure 1).

Conclusion(s): Plasma PG potential is impaired in BDUC patients but not associated with the bleeding score. PG parameters and fibrinogen have a very good ability to distinguish BDUC and HC.