Experience with anticoagulants.

Rokitansky and others on the pathogenesis of thrombosis and embo-lism produced no specific clues leading to a sound method of treatment for these deadly and disabling complications of disease.' Just 24 years ago Morawitz made the following statement. "Even today it is still a thankless task to discuss the problem of thrombosis on the sickbed; thrombosis has lost none of its danger ; it is still a fearsome disease, a frightening spectre to the surgeon and the physician. We still seek vaguely hither and thither for prophylactic and therapeutic measures." To one working in the field of cardiovascular diseases , the lack of agents with which to combat the thrombosing process was a constant source of frustration. Heparin was theoretically available after McLean IS2 discovery and Howell 's early work3 but actually this was not true because of the difficulty of preparation, the impurity of the product, the severe reactions which forbade its use in man, and the great expense involved in producing small amounts. It was therefore an interesting tool for the laboratory but not safe for man. Best, Scott, and Charles had taken the first major step toward producing a heparin suitable for use in man in 1934, but it was not available for general use for another 5 years. When, therefore, in 1938 I lay in bed for 4 months harassed by a severe thrombophlebitis which occurred after an appendectomy, and which finally burned itself out after producing almost daily fevers of 102 to 103 F. and a total loss of 60 pounds in weight, I had both time and special cause for contemplation on this subject. The same year we learned that Best and his co-workers4' 5 had succeeded in producing satisfactory heparin in sufficient quantities so that it could be used in the treatment of thrombosis in man without the risk of severe reaction, provided careful control of the clotting time was observed. In the fall of 1938 a young man (A. S.), aged 31, was seen in consultation with Drs. 1Leo Mayer and Jerome Marks. He had been suffering from an intractable and migrating thrombophlebitis which had involved the veins of the legs and the superficial veins of the trunk. In addition, there was clinical evidence of involvement of the mesenteric, splenic, renal, and probably pulmonary ve-nous systems. Available treatment had failed to change the progressive course of this disease. Drs. Best and Murray …