ACTIVATED PROTEIN-C RESISTANCE AND Q506 MUTATION OF FACTOR-V IN VENOUS THROMBOEMBOLISM

Objectives: to evaluate the prevalence of and relative risk associated with activated protein C resistance and Q506 mutation of factor V in patients with venous thromboembolism, and to determine whether these a bnormalities are associated with specific clinical presentations. Meth ods: prospective case-control prevalence study in 92 patients with ven ous thrombosis. Sensitivity to activated protein C was evaluated based on the ratio of the activated partial thromboplastin times with and w ithout exogenous activated protein C; this index was considered normal if it was above the lower limit of the confidence interval in healthy individuals, i.e., 2.00. The Q506 mutation of factor V (Factor V Leid en), which is among the causes of activated protein C resistance, was looked for using gene amplification followed by nondenaturing gradient gel electrophoresis. Results: Twenty patients (22%) had activated pro tein C resistance, and 16 of these 20 (17.4% of the total) had factor V Leiden (four homozygous and 12 heterozygous mutations). Only four co ntrols had activated protein C resistance, including two who were hete rozygotes for Q506 (P=0.002). The relative risk of venous thrombosis a ssociated with the Q506 mutation was 9. Homozygotes were more likely t o develop pulmonary embolism (P<0.03). Recurrences were more common in patients with the mutation (69% vs 32%, P<0.01). All other characteri stics were similar between heterozygotes and patients without the muta tion. Conclusions: activated protein C resistance due to the Q506 muta tion of factor V is the most common coagulation disorder in venous thr ombosis and does not seem to indicate increased severity, except perha ps in homozygotes. Screening for the factor V Q506 mutation can allow appropriate prophylactic therapy.