Deciphering the mystery of combined factor V and factor VIII deficiency

In 1954 Oeri et al. [1] described two young siblings with a lifelong history of a bleeding tendency related to a deficiency of both factor (F) V and FVIII. Reports of additional families in the late 1950s and 1960s [2–6] suggested that the common occurrence of FV and FVIII deficiencies was not a mere coincidence of parahemophilia and hemophilia A. This was further supported by the observation that in five of the eight families reported up to 1969, the affected individuals were descendents of parental consanguinity [5,6]. How could one explain the mechanism of an inherited disorder involving a gene located on the X-chromosome, and another gene located on an autosome? This enigma has attracted the interest of investigators in subsequent years who felt that understanding the pathogenesis of the disorder might shed light on the molecular genetics, synthesis, secretion, and biochemistry of FV and FVIII. The authors of this historical review were among those investigators who entered the arena, Uri Seligsohn in 1967, and David Ginsburg in 1995.