Resistance to activated protein C (RPCa) is an anomaly described by Dahlbäck in 1993.
Bertina discovered in 1994 the presence of a mutation in the factor V (FV) gene.
This mutation leads to the replacement at position 506 of an arginine by a glutamine (Arg506Gln), which affects one of the sites of cleavage of FV by PCa.
As a result, FV "resists" inactivation by PCa. The mutated FV is referred to as FV Leiden. This factor V loses its function as a cofactor of the protein C system, that is to say of a system which inhibits coagulation; on the other hand, it retains its procoagulant properties. There are other cases of mutations related to the resistance of activated protein C.