INHERITED RESISTANCE TO ACTIVATED PROTEIN-C CAUSED BY PRESENCE OF THEFV Q(506) ALLELE AS A BASIS OF VENOUS THROMBOSIS/

Inherited resistance to activated protein C (APC) was recently discove red as a cause of familial thrombophilia and is now known to be the mo st common genetic risk factor for venous thrombosis. In a majority of cases, APC resistance is associated with a single point mutation in th e factor V gene, which results in substitution of arginine (R) at posi tion 506 by glutamine (Q) (FV:Q(506)). The mutation renders factor Va partially resistant to degradation by activated protein C (APC), which leads to a hypercoagulable state and a life-long 5-10-fold increased risk of venous thrombosis. The previously known inherited deficiencies of antithrombin, protein S or protein C, are in western societies tog ether found in less than 10-15% of thrombosis patients, whereas APC re sistance is present in 20 to 60% of the patients. A functional APC res istance test, which includes predilution of the patient plasma with fa ctor V deficient plasma, is 100% sensitive and specific for the presen ce of FV:Q(506). The FV:Q(506) allele is common in populations of Cauc asian origin (prevalence ranging between 1 and 15%), whereas it is not found in certain other ethnic groups such as in Japanese and Chinese. The thrombotic risk in individuals with APC resistant may be further increased by other genetic defects such as protein C or protein S defi ciency and by exposure to circumstantial risk factors such as oral con traceptives, pregnancy, immobilisation and surgery.