Anticoagulant factor V: factors affecting the integration of novel scientific discoveries into the broader framework.

Since its initial discovery in the 1940s, factor V has long been viewed as an important procoagulant protein in the coagulation cascade. However, in the later part of the 20th century, two different scientists proposed novel anticoagulant roles for factor V. Philip Majerus proposed the first anticoagulant function for factor V in 1983, yet ultimately it was not widely accepted by the broader scientific community. In contrast, Björn Dahlbäck proposed a different anticoagulant role for factor V in 1994. While this role was initially contested, it was ultimately accepted and integrated into the scientific framework. In this paper, I present a detailed historical account of these two anticoagulant discoveries and propose three key reasons why Dahlbäck's anticoagulant role for factor V was accepted whereas Majerus' proposed role was largely overlooked. Perhaps most importantly, Dahlbäck's proposed anticoagulant role was of great clinical interest because the discovery involved the study of an important subset of patients with thrombophilia. Soon after Dahlbäck's 1994 work, this patient population was shown to possess the factor V Leiden mutation. Also key in the ultimate acceptance of the second proposed anticoagulant role was the persistence of the scientist who made the discovery and the interest in and ability of others to replicate and reinforce this work. This analysis of two different yet similar discoveries sheds light on factors that play an important role in how new discoveries are incorporated into the existing scientific framework.

The discovery of factor V: a tricky clotting factor.

The paper tells the story of how FV was discovered in 1943 and installed into the Morawitz theory, a dogma that had reigned the clotting field since 1905 without serious challenges. It is a witness to the fact, many times experienced throughout scientific history, that seminal achievements may arise from serendipity under awkward conditions. Under the worst of circumstances, only a brilliant mind, scientific curiosity and devotion, could the challenge Owren met in Mary's bleeding problem, lead to such a pivotal result. On top of establishing a new clotting factor, his work spurred an unprecedented activity in the field. The thorny road to the new factor's place and role in the clotting mechanism is depicted in some detail. But the factor turned out to be more capricious than its role in coagulation seemed to indicate. Thus, in recent times it has become clear that its platelet counterpart plays an additionally important role in hemostasis as a whole. The two polymorphisms of clinical importance discovered in platelet FV lead to a bleeding disorder, whereas one in plasma FV leads to a rather frequent venous thromboembolic state. Further surprises might therefore be expected from this chameleon of a factor - reflecting the increasingly appreciated tendency that one biological compound appears in different roles.