Mechanisms of the Factor V Leiden Paradox

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 28; no. 10; pp. 1872 - 1877
• Main Authors: van Stralen, K J, Doggen, C J.M, Bezemer, I D, Pomp, E R, Lisman, T, Rosendaal, F R
• Format: Journal Article
• Language: English
• Published: United States American Heart Association, Inc 01.10.2008
• Subjects: Adult; Aged; Blood Coagulation - genetics; Blood Coagulation Disorders, Inherited - blood; Blood Coagulation Disorders, Inherited - complications; Blood Coagulation Disorders, Inherited - genetics; Blood Coagulation Disorders, Inherited - pathology; Blood Coagulation Tests; Case-Control Studies; Factor V - genetics; Female; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Netherlands; Odds Ratio; Population Surveillance; Pulmonary Embolism - blood; Pulmonary Embolism - genetics; Pulmonary Embolism - pathology; Risk Assessment; Risk Factors; Surveys and Questionnaires; Veins - pathology; Venous Thrombosis - blood; Venous Thrombosis - genetics; Venous Thrombosis - pathology; Netherlands
• ISSN: 1079-5642; 1524-4636
• DOI: 10.1161/ATVBAHA.108.169524

OBJECTIVE—Carriers of the factor V Leiden mutation (FVL-carriers) have a substantially increased risk of deep venous thrombosis (DVT), whereas the risk of pulmonary embolism (PE) is only mildly increased compared with noncarriers. So far few studies have investigated possible mechanisms for this so-called FVL paradox. METHODS AND RESULTS—Consecutive patients with a first DVT or PE were included in a large population-based case–control study (MEGA study). Patients, aged 18 to 70 years, provided a questionnaire, DNA (n=3313), or plasma (n=1474). Surgery, injury, and travel were considered thrombosis-provocative. Of 2063 patients with isolated DVT, 20% were FVL-carrier, as were 8% of the 885 patients with isolated PE. Among DVT patients, FVL-carriers had their thrombi more often proximal and a higher number of affected veins than noncarriers. No differences were observed between FVL-carriers and noncarriers in time between provocation and diagnosis, in vitro coagulation time, and thrombus density. Compared with patients with both DVT and PE, isolated DVT patients more often had thrombi located distally and had a similar number of affected veins. Compared with isolated PE patients, isolated DVT patients had a similar time between provocation and diagnosis, and similar in vitro coagulation time and thrombus density. CONCLUSION—Although some effects were differential for FVL-carriers and noncarriers, and some were differential for PE and DVT patients, none of the potential mechanisms offered a clear explanation.