Further Experience With the Use of Thrombin as a Hemostatic Agent ∗

Abstract

We have recently reported animal experiments 1 on the use of purified thrombin 2 as a hemostatic agent. We are now able to obtain thrombin solutions free of bacteria, and with minor loss of activity, by use of fritted glass filters. 3 We wish to report additional toxicity experiments; also preliminary experience with the use of thrombin in a small group of human cases.

Toxicity Experiments. As pointed out previously, 1 thrombin, applied to operative surfaces, is non-toxic. Numerous other toxicity experiments with thrombin have since been performed, and a small group of these is presented below.

(1) Intramuscular administration. An injection of 6000 units into the thigh muscles of an adult rat produced no local thrombosis, and no clinical evidence of toxicity. Blood samples drawn several hours later showed no alteration in the plasma fibrinogen or prothrombin levels.

(2) Intraperitoneal administration. An injection of 6000 units of thrombin (4 cc) caused some uneasiness in a 300 g rat, possibly because the solution was hypotonic. The blood, 6 hours later, showed almost complete disappearance of the fibrinogen, and a 50% reduction in the plasma prothrombin. Intraperitoneal injection of 1500 units into a 200 g rat produced a very slight reduction in the plasma fibrinogen; 700 units had no effect. A proportionate dose in man would be at least 100 cc of concentrated thrombin solution.

(3) Intravenous administration. Rapid injection of 0.5 cc thrombin (250 units) into the jugular vein of a 300 g rat resulted in death in 60 seconds. Thrombi were found in the right ventricle and in the pulmonary artery. Injection of 100 units into a 285 g rat produced no obvious disturbance.

Thrombin, intravenously, is highly dangerous, yet the rat will tolerate larger amounts than one might expect, for 100 units of thrombin will clot 50 cc of oxalated blood in vitro in 16 seconds.