CLINICAL PROGRESS Spontaneous Hemorrhage with Anticoagulants

ANTICOAGULANTS have been used clinically for the past 25 years, starting with the initial work of Murray anld Best,' and their use has inereased steadilv and continuously each year since that time. Fairly early. however, there were reports of spontaneous hemorrhage from the use of anticoagulants. With the introduction and widespread use of the indirect anticoagulants reports of hemorrhage increased and now appear routinely. The introduction of the use of aliticoagulants was based on the experimental work of Murray, Jaques, Perrett, and Best2 in animals. In their report that heparin would suecessfully prevent the formation of a thronbus, these authors did not draw attention to another finding of equal clinical importance. In view of the universal misgivings regarding the possibilitv of hemorrhage with the admninistration of anticoagulants, hem-orrhage was carefully watched for in all the experimental animals. At that time, it was assumed that if the clotting time was so prolonged that the blood was inicoagulable, the subject would die of hemorrhage. However, hemorrhage was not found in any of the several hundred animals used in the study, some of which received very large doses of the anticoagulant. This was also found in the introduction of the indirect anticoagulants (Dicumarol, phenylindanedione, etc.). In mnaniv experiments in animals with phenylindanedione, we maintained the prothrombin time at values of 2 to