ABSTRACT
THE DISCOVERY OF HEPARIN AND ITS FIRST CLINICAL USE The following account of the discovery and fi rst clinical development of heparin was recorded by the physiologist Best (1959), a codiscoverer of insulin as well as a pioneer in the studies of heparin. Incidentally, in 1916, while working at Johns Hopkins University to characterize procoagulant substances, McLean (1916) identifi ed a natural anticoagulant substance. Further studies of this material were performed by his supervisor, Dr. Howell, who coined the term, “heparin” to indicate its fi rst extraction from animal hepatic tissues (Gr. η′ παρ [hepar], liver) (Howell and Holt, 1918). Despite its in vitro anticoagulant action, the inability of heparin to prevent plateletmediated thrombosis (Shionoya, 1927) made it uncertain whether it had antithrombotic potential. However, animal (Mason, 1924) and human studies (Crafoord, 1937) showed that heparin could prevent thrombosis. By the 1950s, heparin was established as an important therapeutic agent in the treatment of venous and arterial thrombosis.
THE PARADOX OF HEPARIN AS A POSSIBLE CAUSE OF THROMBOSIS Weismann and Tobin On June 1, 1957, at the Fifth Scientifi c Meeting of the International Society of Angiology (North American Chapter) in New York, two physicians suggested that heparin might cause arterial embolism in some patients. Rodger E. Weismann, a 43-year-old Assistant Professor of Clinical Surgery at the Dartmouth Medical School (Fig. 1.1), and his Resident in Surgery, Dr. Richard W. Tobin, presented their 3-year experience with 10 patients who developed unexpected peripheral arterial embolism during systemic heparin therapy at the Mary Hitchcock Memorial Hospital, in Hanover, New Hampshire. Their fi rst patient with this complication was reported in detail, and to this day represents a classic description of the syndrome:
