title: Development of a new test for the global fibrinolytic capacity in whole blood.
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.
  
  
  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 3 h at 37 degrees 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 microg 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.
  
  
  CONCLUSIONS
  The new test represents a global assessment of the main fibrinolytic factors in plasma and potentially those associated with blood cells.
authors.affiliation: Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands. d.rijken@erasmusmc.nl
authors.forename: D C
authors.initials: DC
authors.lastname: Rijken
authors.forename: E
authors.initials: E
authors.lastname: Hoegee-de Nobel
authors.forename: A F H
authors.initials: AF
authors.lastname: Jie
authors.forename: D E
authors.initials: DE
authors.lastname: Atsma
authors.forename: M J
authors.initials: MJ
authors.lastname: Schalij
authors.forename: W
authors.initials: W
authors.lastname: Nieuwenhuizen
mesh_terms: D007611:Aprotinin / Q000494:pharmacology; D019411:Clinical Laboratory Techniques; D015444:Exercise; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis*; D005340:Fibrinogen / Q000032:analysis; D005342:Fibrinolysis; D006487:Hemostasis; D006801:Humans; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis; D013917:Thrombin / Q000494:pharmacology; D010959:Tissue Plasminogen Activator / Q000032:analysis
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; D017395:Plasminogen Activator Inhibitor 1; D005340:Fibrinogen; D007611:Aprotinin; D013917:Thrombin; D010959:Tissue Plasminogen Activator