Plasmin generation analysis in patients with bleeding disorder of unknown cause.

Autor:	Mehic D; Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria., Reitsma SE; Department of Pathology and Laboratory Medicine, UNC Blood Research Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC., de Moreuil C; Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.; UMR 1304, GETBO, Université de Bretagne Occidentale, Brest, France.; Internal Medicine, Vascular Medicine and Pneumology Department, Brest University Hospital, Brest, France., Haslacher H; Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria., Koeller MC; Department of Pathology, Medical University of Vienna, Vienna, Austria., de Laat B; Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.; Synapse Research Institute, Maastricht, The Netherlands., Ay C; Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria., Pabinger I; Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria., Wolberg AS; Department of Pathology and Laboratory Medicine, UNC Blood Research Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC., Gebhart J; Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2024 Nov 12; Vol. 8 (21), pp. 5663-5673.
DOI:	10.1182/bloodadvances.2024012855
Abstrakt:	Abstract: Bleeding disorder of unknown cause (BDUC) is a diagnosis of exclusion after evaluation of plasma coagulation and platelet function. Patients with BDUC (n = 375) recorded in the Vienna Bleeding Biobank were analyzed in comparison with healthy controls (HCs; n = 100) in this case-control study. Plasmin generation (PG) parameters were analyzed using calibrated fluorescence detection in citrated plasma. Turbidimetric plasma clot formation/lysis of 293 (78%) patients with BDUC and confocal microscopy of clots from representative patients with BDUC (n = 6) and HCs (n = 9) were assessed. In the PG analysis, patients with BDUC exhibited lower velocity and peak plasmin levels but a higher endogenous plasmin potential than HCs. Peak plasmin levels correlated with maximum clot absorbance but not with clot lysis time. Clot absorbance is an indicator of clot fiber density. Confocal microscopy analysis revealed a tendency towards thicker fibers in clots of patients with BDUC, which negatively correlated with peak plasmin (r = -0.561; P = .030). Peak plasmin correlated weakly with factor XIII, but not with other fibrinolytic factors (alpha2-antiplasmin, thrombin activatable fibrinolysis inhibitor, or plasminogen activator inhibitor 1) or bleeding severity. A model comprising fibrinogen and parameters of PG yielded high predictive power in discriminating between patients with BDUC and HCs across a fivefold stratified cross validation (80% of data; mean area under the curve [AUC], 0.847). The model generalized well to unseen data (20% of data; AUC, 0.856). Overall, patients with BDUC counterintuitively exhibited reduced peak plasmin levels, potentially related to altered clot structure. (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
Databáze:	MEDLINE
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