Fathers of modern coagulation.

Thromb Haemost 2007; 98: 3–5 The best contribution we could make for the 50 th anniversary of Thrombosis and Haemostasis, the former official journal of the International Society on Thrombosis and Haemostasis (ISTH), was to recount the history of some of the people who opened the door to major advances in coagulation research. Many of these people were among the first to contribute articles to the Journal which was initially named Thrombosis et Diathesis Haemorrhagica. The story begins in the early 1950s shortly after the end of the second World War. In the late 1940s through the 1950s, scientists from several nations made major breakthroughs in our understanding of the mechanism of coagulation. This was largely due to the discovery of several new clotting factors. In 1945 the major clotting theory rested on that of Morawitz as shown in Figure 1 (1). Prothrombin was known to be converted to thrombin in a reaction that required both thromboplastin (now know as tissue factor) and platelets. In addition, in 1935, Patek and Taylor described antihaemophilic factor as a component of plasma lacking in patients with classic haemophilia (2), and Kenneth Brinkhous and his colleagues at Iowa showed that this factor was necessary for the rapid conversion of prothrombin to thrombin. Thrombin was also known to convert fibrinogen to fibrin. Also, in 1944, Kenneth Robbins described fibrin stabilizing factor, now known as factor XIII (3). After these observations, things began to change rapidly as new factors were discovered. The trouble was that each new factor was given several names and even some of the older known factors had several names as shown in Table 1. Looking at the different names for the same substance, it is easy to understand how nomenclature could affect ones interpretation of results, and because of this an international committee was formed in 1954 in an effort to establish a common nomenclature for the clotting factors. This committee was first termed “The International Committee on Nomenclature of Blood Clotting Factors”. The first meeting of this Committee was held in Basel and subsequent meetings were held in Copenhagen, Boston and Rome. Figure 2 shows the members of the Committee who attended the Rome meeting in 1958. It was at this meeting that most of the members agreed to use Roman numerals for the clotting factors. The legend of Figure 2 gives the names of those who were present at the meeting. Some members, namely, Gwynne Macfarlane, Rosemary Biggs, Oscar Ratnoff, and Paul Aggeler were apparently absent from the meeting, but their influence was felt. While all of the members of the Committee in Figure 2 are shown with smiles on their faces, the discussions leading to decisions on nomenclature were often heated and forceful (4). Most of the men shown in Figure 2 are legendary for their contributions to the field of coagulation. H. Jensen (#1), who worked at the US Army Research Labs, studied the proteases in coagulation looking at the balance between proteolytic action (thrombin generation and fibrinolysis) and anti-proteolytic action. Walter Seegers (#2) had isolated prothrombin and had discovered several other vitamin-K-dependent factors in his prothrombin preparation which he called “auto” prothrombins because he viewed them as being derived from prothrombin. His obsession with the autoprothrombin nomenclature probably obscured much of his original discoveries, since it appears that he actually characterized what later came to be known as factor IX, factor X, factor Xa, and activated protein C, among others. He also called Owren’s proaccelerin (factor V) “AC (accelerator) globulin”. Erik Jorpes (#3), from the Karolinska Institute in Sweden, was interested in all the clotting proteins but was particularly engaged by the actions of heparin. Dr. Jorpes also recruited Birger and Magareta Blombäck who worked on both fibrinogen and factor VIII. Fritz Koller (#4), who discovered factor X with Francois Dukert (5), was one of the first Editors of the Journal. Erwin Deutsch (#5), in addition to his work on anticoagulants, was the main person who started the journal Thrombosis et Diathesis Haemorrhagica, the journal that later became Thrombosis and Haemostasis which was the official journal of the ISTH for several years. Jean-Paul Soulier (#6) developed the so-called PPSB (Prothrombin-Proconvertin-Stuart factor-antihaemophilic factor B) fraction used for treatment of haemophilia B. Karl Lenggenhager (#7), in addition to work on haemophilia, performed early studies on both platelets and antithrombin. Paul Owren (#8) discovered factor V, which he called proaccelerin, in 1944 during the Nazi occupation of Norway, but his publication was delayed until 1947 (6). Louis B. Jaques (#9) 50 th A n n iv er sa ry (1 95 7– 20 07 )