Duration of Anticoagulant Action of Heparin in Vivo in Relation to Dosage.

Abstract

Reed 1 determined experimentally the “minimum dependable dose” of heparin as an anticoagulant. Takuji Shinoya, 2 upon injecting heparin intravenously into dogs, commented on the rapidity with which the coagulation time increased and then returned to normal. In the following experiments determinations were made of the rate of appearance and disappearance of the anticoagulant action of heparin in vivo.

Heparin was injected in varying amounts into the ear veins of rabbits, and the blood was collected from cut veins of the opposite ears. One method of determining clotting time which was used is as follows: Drops of blood were collected at intervals of 20 seconds or more upon glass slides cleaned with alcohol and ether. The time when each drop fell upon the slide was noted. Only blood which exuded and dropped readily was used. The blood was termed clotted when, upon being moved with a wire loop, clear or nearly clear serum was left behind. The slides were kept in a moist chamber at room temperature. A simpler method, used in the later series of experiments, is the capillary tube method. These 2 methods were used interchangeably without variations in results. The data of such an experiment are given in Table I.

The clotting time was increased to more than 4 hours as soon as 30 seconds after the injection of heparin. Within 20 minutes after the injection, the clotting time began to return toward normal. The normal clotting time was reached within one and a half hours from the time of injection.