Experimental and Clinical Studies on the Antifibrinolytic and Presumed Antithrombotic Effect of a Kallikrein Inhibitor (Trasylol)

Abstract

A method to prevent both bleeding and thrombo-embolism after prostatectomy by combining -ACA and heparin was introduced by Andersson. Recently some authors have reported that a kallikrein inhibitor, Trasylol, combines antifibrinolytic and anti-thrombotic properties. We therefore investigated, in vitro and in vivo, the ability of Trasylol to inhibit coagulation and fibrinolytic activity. We also studied the effect of Trasylol in connection with prostatectomy.

Our studies led to the following conclusions:

1. Trasylol is a fibrinolytic inhibitor, which in vivo acts mainly by inhibiting the activation of plasminogen. An inhibitory effect of plasminogen activation was demonstrated down to a concentration of 2 units per ml. In a tenfold higher concentration, Trasylol acted also as an antiplasmin.

2. Trasylol in concentrations of 10–100 units per ml citrated blood had no influence on the platelet count, platelet adhesiveness, one-stage prothrombin time, recal-cification time or thrombin time. The plasma levels of AHF, f. IX, P &P, f. V and fibrinogen also remained unchanged. In a concentration of about 1000 units per ml Trasylol had a weak antithromboplastic effect.

Coagulation analyses after prostatectomy revealed no difference between the values obtained in 7 controls and those found in 14 patients treated with Trasylol (100,000 units 3 times daily).

3. Metabolic studies showed that the half-life of Trasylol in serum was short, about 30 minutes. It was not excreted in active form in the urine.

4. Trasylol was given to 14 patients in connection with prostatectomy, and during the following 5 postoperative days (100,000 units 3 times daily). It had no effect on the postoperative bleeding. Signs of thrombosis occurred in 3 of these 14 patients, which is the same frequency as in our control series.

5. In conditions with proteolytic activity in the circulating blood, Trasylol is probably just as effective as -ACA or AMCA. But since no antithrombotic effect could be demonstrated in vivo, Trasylol appears to offer no advantages over -ACA and AMCA, especially in association with surgery on the urinary tract, where inhibition of the fibrinolytic activity in the urine is desired.

6. As prophylaxis against bleeding and thromb-embolism after prostatectomy, Trasylol is ineffective.