Factor V Cambridge:: A new mutation (Arg306→Thr) associated with resistance to activated protein C

A new factor V mutation associated with resistance to activated protein C and thrombosis (factor V Cambridge, Arg(306)-->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 Gln(506) mutation. The Arg(306) 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 Arg(679) 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 VThr(306) is the first description of a mutation affecting the Arg(306) APC cleavage site and is the only mutation, other than factor V Leiden (Arg(506)-->Gln), that has been found in association with APC resistance. This finding confirms the physiologic importance of the Arg(306) 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. (C) 1998 by The American Society of Hematology.