Contact activation prolongs clot lysis time in human plasma: role of thrombin-activatable fibrinolysis inhibitor and Factor XIII.
BACKGROUND
Contact activation system proteins (e.g., Factor XII, kallikrein) have been implicated as direct or indirect activators of plasminogen. However, contact activation and Factor XI have enhanced thrombin-activatable fibrinolysis inhibitor (TAFI) activation and decreased fibrinolysis, and Factor XIII (FXIII) also delays fibrinolysis via alpha(2)-anti-plasmin deposition on fibrin polymers. Thus, the goals of this study were to define how fibrinolysis is modulated in human plasma by contact or tissue factor (TF) activation, and what role TAFI and FXIII plays in this system.


METHODS
Normal, TAFI-deficient and TAFI-deficient/FXIII-supplemented plasma was exposed to tissue-type plasminogen activator and activated with either celite or TF. Clot growth/disintegration kinetics were documented with thrombelastography.


RESULTS
Normal plasma activated with celite had significantly prolonged onset and duration of clot lysis compared with samples activated with TF. TAFI-deficient plasma activated with celite was noted to have a duration of clot lysis not different from samples activated with TF, but a significant difference in time to onset of lysis persisted. Celite activation of TAFI-deficient/FXIII-supplemented plasma showed significantly prolonged onset and duration of clot lysis compared with samples activated with TF.


CONCLUSIONS
Primarily TAFI, and to a lesser extent FXIII, contributed to contact system protein-mediated attenuation of fibrinolysis. Clinical investigation of these phenomena is warranted in clinical settings involving contact activation (e.g., intra-aortic balloon pumps and ventricular assist devices) to determine whether these devices modulate fibrinolysis and perhaps contribute to thromboembolic morbidity.
Nielsen
Vance G
VG
Department of Anesthesiology, University of Alabama at Birmingham, 619 South 19th Street, Birmingham, AL 35249-6810, USA. vnielsen@uab.edu
Steenwyk
Brad L
BL
Gurley
William Q
WQ
D025901:Carboxypeptidase B2 / Q000097:blood / Q000172:deficiency / Q000502:physiology*; D007692:Diatomaceous Earth / Q000494:pharmacology; D005176:Factor XIII / Q000494:pharmacology / Q000502:physiology*; D005342:Fibrinolysis / Q000187:drug effects / Q000502:physiology*; D006490:Hemostatics / Q000494:pharmacology; D006801:Humans; D010949:Plasma / Q000187:drug effects / Q000502:physiology*; D010960:Plasminogen Activators / Q000502:physiology*; D013916:Thrombelastography; D013925:Thromboplastin / Q000494:pharmacology / Q000502:physiology*; D010959:Tissue Plasminogen Activator / Q000494:pharmacology
D006490:Hemostatics; D007692:Diatomaceous Earth; D005176:Factor XIII; D013925:Thromboplastin; D025901:Carboxypeptidase B2; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator