Mechanisms of the Factor V Leiden Paradox

K.J. van Stralen, Catharina Jacoba Maria Doggen, I.D. Bezemer, E.R. Pomp, T. Lisman, F.R. Rosendaal

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Abstract

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. Carriers of the factor V Leiden mutation have substantial risk of deep venous thrombosis but a mild pulmonary embolism risk. Five potential mechanisms were explored; thrombus location, number of affected veins, time between provocation and diagnosis, in vitro coagulation time, and thrombus density. None of the mechanisms offered a clear explanation
Original languageEnglish
Pages (from-to)1872-1877
Number of pages6
JournalArteriosclerosis, thrombosis and vascular biology
Volume28
Issue number10
DOIs
Publication statusPublished - 2008

Keywords

  • IR-76888

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    van Stralen, K. J., Doggen, C. J. M., Bezemer, I. D., Pomp, E. R., Lisman, T., & Rosendaal, F. R. (2008). Mechanisms of the Factor V Leiden Paradox. Arteriosclerosis, thrombosis and vascular biology, 28(10), 1872-1877. https://doi.org/10.1161/ATVBAHA.108.169524