Anticomplementary Action of Purified Heparin.

Abstract

The writers, in a previous paper, 1 reported on the anticomplementary action of heparin. It was found that the antihemolytic effect is not due to an action upon the erythrocytes. Although an ancillary action upon amboceptor could not be excluded, the action was found to be upon the complement. Further investigation demonstrated that the anticomplementary effect of heparin is due to its interference with the heat-stable factor or the so-called third component of complement. Complement inactivated by heat and by NH₃, containing in both instances the third component, reactivates heparin-inactivated complement. Previous admixture of a small amount of calcium to heparin destroys its anticomplementary activity without interfering with its anticoagulant action. It was found that a large amount of heparin is required to inhibit complement, many times the dose that will render a corresponding amount of blood incoagulable. This is also pointed out by Hyde. 2 Intracardiac injections of guinea pigs with as much as 50 mgm. of heparin led to incoagulability of the blood without impairment of complement titer. An anticomplementary action of heparin is reported by Fuchs and Hartman. 3 Prof. Howell's announcement 4 of the preparation of N-free heparin, suggested an investigation to determine whether or not the anticomplementary power is due to heparin per se or to the impurities associated with it. Furthermore, the possibility that the anticoagulant effect and the anticomplementary power depend upon 2 different mechanisms also indicated more work in that direction.

Through the courtesy of Prof. Howell, who kindly prepared for us a small amount of purified heparin, and to whom we are much indebted, we are enabled to report results obtained with the purified product. The anticomplementary power of purified heparin was retained and the action was again found to be upon the heat stable fraction of the complement. Complement, inactivated by heat and by NH₃, reactivates the complement inactivated by purified heparin. While 0.18 mgm. of the crude heparin inactivated one unit of complement, 0.013-0.018 mgm. of the purified product produced the same effect. The anticomplementary power of the purified heparin was increased about 10 fold.