Resistance to activated protein C caused by a factor V gene mutation.
Each year, approximately one in 1000 individuals suffers from venous thromboembolism. The pathogenesis of the disease is multifactorial and a thrombotic event is the result of a combination of genetic and circumstantial risk factors. Until recently, genetic defects could only be identified in a minority of thrombosis patients. The discovery of inherited resistance to activated protein C as a risk factor for thrombosis changed the situation for the better. In Western countries, activated protein C resistance is found in 20% to 60% of patients with thrombosis. Activated protein C resistance is caused by a single point mutation in the Factor V gene, leading to replacement of Arg(R)506 in the activated protein C cleavage site of Factor V with a Gln(Q). As a result, the activated protein C-mediated cleavage and inhibition of mutated Factor V (FV:Q506) is impaired, which leads to increased thrombin generation, a hypercoagulable state, and a life-long increased risk of thrombosis.
Zöller
B
B
University of Lund, Malmö General Hospital, Sweden.
Dahlbäck
B
B
D000368:Aged; D000925:Anticoagulants / Q000494:pharmacology*; D004351:Drug Resistance / Q000235:genetics; D005165:Factor V / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D017354:Point Mutation; D011486:Protein C / Q000494:pharmacology*; D012307:Risk Factors; D013924:Thrombophlebitis / Q000235:genetics*
D000925:Anticoagulants; D011486:Protein C; D005165:Factor V