Title
Development of a new test for the global fibrinolytic capacity in whole blood
Author
Rijken, D.C.
Hoegee-de Nobel, E.
Jie, A.F.H.
Atsma, D.E.
Schalij, M.J.
Nieuwenhuizen, W.
TNO Kwaliteit van Leven
Publication year
2008
Abstract
Background: The development of global tests for the fibrinolytic capacity in blood is hampered by the low base-line fibrinolytic activity in blood, by the involvement of both plasmatic components and blood cells in the fibrinolytic system and by the loss of fibrinolytic activity as a result of the action of plasminogen activator inhibitor-1 (PAI-1). Objective: To develop a new test for the global fibrinolytic capacity (GFC) of whole blood samples. Methods and results: Collection of blood in thrombin increased the subsequent generation of fibrin degradation products. This was ascribed to rapid clot formation and concomitant reduction of in vitro neutralization of tissue-type plasminogen activator (tPA) by PAI-1. On the basis of this observation, the following test was designed: blood samples were collected in thrombin with and without aprotinin and clots were incubated for 3h at 37°C. The GFC was assessed from the difference between the fibrin degradation products in the two sera. The assay was applied to blood samples from patients and healthy subjects. Other hemostasis parameters were determined in plasma samples taken simultaneously. The GFC varied considerably (normal range 0.13-13.6 μg mL-1); physical exercise strongly increased the GFC. Statistically significant correlations were found with tPA activity, PAI-1 activity and fibrinogen level. A mixture of antibodies against tPA and urokinase-type plasminogen activator (uPA) completely inhibited the GFC. An inhibitor of activated thrombin-activatable fibrinolysis inhibitor (TAFI) accelerated fibrinolysis 8-fold. Conclusion: The new test represents a global assessment of the main fibrinolytic factors in plasma and potentially those associated with blood cells. © 2007 International Society on Thrombosis and Haemostasis.
Subject
Biology
Brinolysis
Global fibrinolytic capacity
Plasminogen activator inhibitor-1
Thrombin-activatable fibrinolysis inhibitor
Tissue-type plasminogen activator
antibody
aprotinin
fibrin
fibrin degradation product
fibrinogen
plasminogen activator inhibitor 1
thrombin
thrombin activatable fibrinolysis inhibitor
tissue plasminogen activator
urokinase
adult
aged
article
blood analysis
blood cell
blood clotting
blood sampling
clinical article
controlled study
correlation analysis
exercise
female
fibrinolysis
global fibrinolytic capacity
hemostasis
human
in vitro study
ischemic heart disease
male
plasma
priority journal
statistical significance
transluminal coronary angioplasty
Aprotinin
Exercise
Fibrin Fibrinogen Degradation Products
Fibrinogen
Fibrinolysis
Hemostasis
Humans
Laboratory Techniques and Procedures
Plasminogen Activator Inhibitor 1
Thrombin
Tissue Plasminogen Activator
To reference this document use:
http://resolver.tudelft.nl/uuid:1af0e4bd-aef3-45d4-a188-898f4bf4b135
DOI
https://doi.org/10.1111/j.1538-7836.2007.02816.x
TNO identifier
240592
ISSN
1538-7933
Source
Journal of Thrombosis and Haemostasis, 6 (1), 151-157
Document type
article