Urokinase induced fibrinolysis in thromboelastography: a model for studying fibrinolysis and coagulation in whole blood

Abstract

The contact system (CS) proteins, factor XII and prekallikrein are thought to have roles in blood coagulation and fibrinolysis. Recent research has suggested that the CS proteins might be more important in fibrinolysis and cell function than in coagulation. Most studies on fibrinolysis have used plasma or euglobulin assays, ignoring the influence of cellular elements of blood on the fibrinolytic process. In order to study both coagulation and fibrinolysis in whole blood (WB), we have developed a thromboelastography (TEG) assay to investigate both coagulation and fibrinolysis in the same blood sample. In this assay, named urokinase (UK) induced fibrinolysis in thromboelastography (UKIFTEG), TEG is performed on recalcified citrated WB in the presence of UK. Large variations in Ly60 (percentage lysis 60 min after clot formation) were obtained between different donors with the same UK concentration. The UKIFTEG assay was therefore performed using UK concentrations that gave Ly60 values in the approximate range of 20-40%. The effect of CS activation was investigated in the presence or absence of celite (10 mg mL(-1) blood). Celite shortened the clotting time (CT), and increased Ly60 values. Factor XIIa (FXIIa) and plasma kallikrein (KK) produced concentration dependent reductions in CT (significant at concentrations of 1303 and 2600 ng mL(-1) blood, respectively) and increased Ly60 values (significant at concentrations of 652 and 1300 ng mL(-1) blood, respectively). Our results show that CS activation and both FXIIa and KK produce reductions in clotting time and enhanced fibrinolysis in UKIFTEG.