Factor XII‐dependent increases in thrombin activity induce carboxypeptidase‐mediated attenuation of pharmacological fibrinolysis

• Published in: Journal of thrombosis and haemostasis 2004-01, Vol.2 (1), p.128-134
• Main Authors: Latacha, M. P., Schaiff, W. T., Eisenberg, P. R., Abendschein, D. R.
• Format: Article
• Language: English
• Subjects: carboxypeptidase; Carboxypeptidase B2 - metabolism; Carboxypeptidases - metabolism; Factor Xa Inhibitors; factor XII; Factor XII - metabolism; Factor XIIa - metabolism; Fibrinolysis - drug effects; Fibrinolytic Agents - pharmacology; Humans; In Vitro Techniques; Streptokinase - pharmacology; Thrombin - antagonists & inhibitors; Thrombin - metabolism; thrombin‐activated fibrinolysis inhibitor; thrombolysis; Tissue Plasminogen Activator - pharmacology
• ISSN: 1538-7933; 1538-7836; 1538-7836
• DOI: 10.1111/j.1538-7836.2004.00538.x

Activation of the contact system in patients treated with fibrinolytic agents may be an important source of thrombin that activates thrombin‐activated fibrinolysis inhibitor (TAFI) and attenuates fibrinolysis. Factor (F)XIIa in plasma increased 2‐fold over 60 min in patients given either tissue plasminogen activator (t‐PA) or streptokinase (SK). To determine whether FXIIa‐mediated generation of thrombin and activated TAFI (TAFIa) attenuates fibrinolysis in vitro, plasma clots were incubated with SK (250 U mL−1) or t‐PA (2.5 g mL−1) and the rate of lysis was measured. Plasma FXIIa impaired lysis judging from marked acceleration when 2.5 µm corn trypsin inhibitor were added (lysis increased by 172 ± 144% for SK and 40 ± 31% for t‐PA vs. no inhibitor, n = 16, P