Heparin. II. Investigation of possible antigenic action. ∗

Abstract

In a previous paper 1 were reported details of experiments on the intravascular use of heparin 2 , 3 , 4 in etherized dogs. These experiments, together with other experiences in preservation of blood samples used for various physical and chemical analyses, have demonstrated the value of this material in laboratory work. It seemed advisable, therefore, to investigate the possibilities of its use in transfusion when, for any reason, there might be delayed injection.

Numerous experiments were undertaken in which large doses of heparin—5 to 60 mg. per kilo of body weight—were injected intravenously in normal dogs and rabbits. In no instance was there any demonstrable gross disturbance of any body function.

It occurred to us, however, that the effects of repeated injections should be investigated. For this purpose, 20 mg. per cc. of heparin were dissolved in Ringer solution and injected into the peritoneal cavity of adult healthy guinea pigs, in relatively large doses, 20 to 60 mg. In a few instances symptoms characterized by prostration and weakness occurred within a few minutes after the first injection. After periods varying from 2 to 3 weeks, transcutaneous and intracutaneous tests were made with a similar solution of heparin, all of which proved negative. A second injection of a comparable dose of heparin was now made. In most cases this proved entirely negative, but in a few instances there occurred symptoms suggestive of anaphylaxis.

These results, together with those noted following the first injection, suggested two possibilities: 1. There might be a protein fraction in the heparin that sensitized certain more susceptible animals. 2. The heparin possessed toxic properties of undetermined nature.

Subsequent employment of fresh lots of heparin uniformly failed on both first and second injections to produce either toxic or anaphylactic symptoms, so that it is possible that the particular lot first used had not been satisfactorily purified.