Cerebral venous thrombosis. Role of activated protein C resistance and factor V gene mutation.

Abstract

The number of well-described familial and acquired conditions that are predisposing factors for thrombosis continues to increase. Although most are uncommon, in 1993 a new condition that has ultimately been recognized as activated protein C resistance (APC-R) was reported.1 This condition is present in approximately half of thrombosis-prone families and has an autosomal dominant inheritance pattern with variable penetrance.2 The genetic basis for APC-R is a point mutation in the coagulation factor V gene at the site where APC inactivates Va (Arg506).3 This common factor V gene mutation (Arg506Gln), also termed factor V Leiden, leads to thrombosis caused by the persistence of a degradation-resistant Va procoagulant in homozygous and heterozygous individuals. Factor V Leiden is seen in 90% of patients with venous thrombosis and APC-R, suggesting that there may be other genetic or functional defects responsible for APC-R in a minority of patients.4 The prevalence of the factor V mutation varies by geography and ethnicity, ranging from 2% to 15% in western societies.4 At present, it is considered to be the most common mutation in the European gene pool, leading Dahlback4 to speculate that it may convey a survival advantage. The clinical significance of the factor V Leiden mutation in peripheral venous thrombosis has now become firmly established. APC-R is found in 20% to 60% of patients with deep venous thrombosis, depending on …