[Activated protein C resistance and venous thrombophilia: molecular genetic prevalence study in the German population].

BACKGROUND AND OBJECTIVE: Resistance against activated protein C (APC), caused by factor V R506Q mutation (factor V Leiden mutation), is among the most important hereditary clotting defects that are associated with an increased risk of venous thrombosis. As there are hardly any data for Germany regarding APC resistance that have been validated by genetic analysis, this study was undertaken to determine the prevalence of factor V Leiden (fVL) mutations in a sizeable group of patients in Germany with venous thromboembolism (VTE) and a control group of healthy persons.

PATIENTS AND METHODS: 1200 consecutive patients (689 females, 511 males) from various regions of Germany were examined who, at an age between 0.1 and 45 years, had developed primary deep vein thrombosis (DVT) and/or pulmonary embolism (PE), as confirmed by imaging tests. The control group consisted of 740 healthy persons (332 females and 408 males; median age 33 years) for whom there was no evidence in their personal or family history of TE. Analysis of the fV-1691 genotype was by Mnll-restriction analysis of genomic fV DNA fragments, amplified by polymerase chain reaction.

RESULTS: The prevalence in the control group was 7.5% the for heterozygotic fV:Q506 mutant (25 females, 30 males). For the patients the prevalence of the fV R506Q mutation was 27.2% (32.1% heterozygotes [165 females, 112 males]; 4.1% homozygotes [33 females, 16 males], i.e. significantly higher than in the healthy controls (P < 0.0001). In 81.3% of the patients with fV:Q506 DVT in the leg-pelvic vein region was found as the first manifestation, thrombosis in an atypical site in 14.4% and isolated PE in 4.3%. The first manifestation had occurred spontaneously in 36% of patients with the fV:Q506 mutant (44 females, 75 males), in 53.1% of homozygotes and in 33.5% of heterozygotic carriers of the mutation.

CONCLUSION: The fV Leiden mutation due to APC resistance is the most common cause of venous thrombosis and apparently one of the most common inherited diseases.