Mechanisms of the factor V Leiden paradox.
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.


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.


CONCLUSIONS
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.
van Stralen
K J
KJ
Department of Clinical Epidemiology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
Doggen
C J M
CJ
Bezemer
I D
ID
Pomp
E R
ER
Lisman
T
T
Rosendaal
F R
FR
D000328:Adult; D000368:Aged; D001777:Blood Coagulation / Q000235:genetics*; D025861:Blood Coagulation Disorders, Inherited / Q000097:blood / Q000150:complications / Q000235:genetics* / Q000473:pathology; D001780:Blood Coagulation Tests; D016022:Case-Control Studies; D005165:Factor V / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D016017:Odds Ratio; D011159:Population Surveillance; D011655:Pulmonary Embolism / Q000097:blood / Q000235:genetics* / Q000473:pathology; D018570:Risk Assessment; D012307:Risk Factors; D011795:Surveys and Questionnaires; D014680:Veins / Q000473:pathology; D020246:Venous Thrombosis / Q000097:blood / Q000235:genetics* / Q000473:pathology
C095381:factor V Leiden; D005165:Factor V