Fibrin-dependent fibrinolytic activity during extracorporeal circulation.

Cardiopulmonary By-Pass (CPB) Surgery may at times induce a haemostatic defect, at present not too well understood, causing severe bleeding from the operative site and chest tube drain. We present here some data on antigen increase in tissue Plasminogen Activator (tPA) and D 2 Dimer (D2D) detected during CPB and apparently not compensated by enhanced Plasminogen Activator Inhibitor type 1 (PAI 1) activity. tPA concentration (antigenic) ranged around 6.15 ng/ml (SD 5.6) before thoracotomy and 5.8 g/ml (SD 4.74) 5-10 minutes after a heparin 250 IU/Kg bolus injection. During CPB, tPA increased to 20.34 ng/ml (SD 9.17) before protamine infusion, and 16.93 ng/ml (SD 8.13) after heparin neutralization. As the D2D went up to 2000-4000 ng/ml (before/after protamine) and it was not correlated by fibrinogen consumption or FDP production, we find these observations suggestive of fibrin-dependent fibrinolytic activity, as an acquired haemostatic defect developed during CPB.

Comparison of thrombolytic, fibrinolytic, and fibrinogenolytic properties of tissue plasminogen activator, streptokinase, single-chain urokinase, high molecular weight and low molecular weight urokinase in human plasma in vitro.

Thrombolytic, fibrinolytic, and fibrinogenolytic properties of tissue plasminogen activator (t-PA) from melanoma cells (mt-PA), recombinant t-PA (rt-PA), streptokinase (SK), single-chain urokinase plasminogen activator (scu-PA), and high and low molecular weight urokinase (HMW UK, LMW UK) were compared in vitro by means of systems using human plasma. Thrombolytic activities were tested on standard or labeled hanging clots. When compared on the basis of urokinase international units, t-PA appeared to be slightly more active than scu-PA and streptokinase, and about 10-fold more active than both preparations of UK when they were diluted in plasma. Fibrinolytic activity was evaluated by measuring the lysis time of recalcified plasma containing variable amounts of thrombolytic agents. t-PA was shown to be twice as active as HMW UK, which was itself more active than LMW UK. When scu-PA and both types of UK were compared on bovine fibrin plates, they showed similar fibrinolytic activity, but the t-PA calibration curve was not parallel to those obtained with UK and scu-PA. Relative thrombolytic and fibrinogenolytic properties were studied for each thrombolytic agent. For similar thrombolytic activities, fibrinogenolysis provoked by scu-PA was less marked than with t-PA and with both UK, while SK showed the highest activity. Our results demonstrate that the thrombolytic/fibrinogenolytic ratio is much more favorable to t-PA and scu-PA than to both forms of UK. Another observation clearly shows that fibrinogenolysis can be induced in vitro in human plasma by high doses of t-PA. This consequence may be important since the therapeutic use of t-PA can be associated with high concentrations of t-PA, and thus t-PA infusion could lead in vivo to severe fibrinogen breakdown. In addition, the methodology described could be useful in standardizing comparison between different species of thrombolytic agents.