on July 10, 2008
Published online before print July 10, 2008, doi: 10.1161/ATVBAHA.108.169524
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Submitted on January 19, 2008
Accepted on June 26, 2008
Mechanisms of the Factor V Leiden Paradox
K. J. van Stralen ;
From the Department of Clinical Epidemiology (K.J.v.S., C.J.M.D., I.D.B., E.R.P., F.R.R.), Einthoven Laboratory for Experimental Vascular Medicine (F.R.R.), and the Department of Thrombosis and Hemostasis (F.R.R.), Leiden University Medical Center, the Netherlands; the Department of Clinical Chemistry and Haematology (T.L.), University Medical Centre Utrecht, The Netherlands; and the Surgical Research Laboratory (T.L.), Department of Surgery, University Medical Centre Groningen, University of Groningen, the Netherlands.
* To whom correspondence should be addressed. E-mail: F.R.Rosendaal{at}LUMC.nl.
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.
Key words: factor V Leiden • pulmonary embolism • deep venous thrombosis • thrombus location • coagulation • thrombus density