A new
factor V mutation associated with resistance to activated
protein C and
thrombosis (
factor V Cambridge, Arg306-->Thr) was found in one patient from a carefully selected group of 17 patients with
venous thrombosis and confirmed
APC resistance in the absence of the common Gln506 mutation. The Arg306 mutation was also present in a first degree relative who also had
APC resistance. Other potential causes of
APC resistance, such as a mutation at the Arg679 site and the
factor V HR2 haplotype, were excluded. Subsequent screening of 585 patients with
venous thromboembolism and 226 blood donors did not show any other individual with this mutation. Factor VThr306 is the first description of a mutation affecting the Arg306 APC cleavage site and is the only mutation, other than
factor V Leiden (Arg506-->Gln), that has been found in association with
APC resistance. This finding confirms the physiologic importance of the Arg306 APC-cleavage site in the regulation of the
prothrombinase complex. It also supports the concept that
APC resistance and
venous thrombosis can result from a variety of genetic mutations affecting critical sites in the
factor V cofactor.