Synergistic Effects of Hypofibrinolysis and
Genetic and Acquired Risk Factors on the Risk of
a First Venous Thrombosis

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Meltzer, Mirjam E. and Lisman, Ton and Doggen, Carine J.M. and Groot de, Philip G. and Rosendaal, Frits R. (2008) Synergistic Effects of Hypofibrinolysis and
Genetic and Acquired Risk Factors on the Risk of
a First Venous Thrombosis.
PLoS Medicine, 5 (5). 0751-0759. ISSN 1549-1277

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Abstract:Background
Previously, we demonstrated that hypofibrinolysis, a decreased capacity to dissolve a blood clot as measured with an overall clot lysis assay, increases the risk of venous thrombosis. Here, we investigated the combined effect of hypofibrinolysis with established risk factors associated with hypercoagulability.

Methods and Findings
Fibrinolytic potential was determined with a plasma-based clot lysis assay in 2,090 patients with venous thrombosis and 2,564 control participants between 18 and 70 y of age enrolled in the Multiple Environmental and Genetic Assessment (MEGA) of risk factors for venous thrombosis study, a population-based case-control study on venous thrombosis. Participants completed a standardized questionnaire on acquired risk factors.

Hypofibrinolysis alone, i.e., clot lysis time (CLT) in the fourth quartile (longest CLT) (in absence of the other risk factor of interest) increased thrombosis risk about 2-fold relative to individuals with CLT in the first quartile (shortest CLT). Oral contraceptive use in women with CLT in the first quartile gave an odds ratio (OR) of 2.6 (95% confidence interval [CI] 1.6 to 4.0), while women with hypofibrinolysis who used oral contraceptives had an over 20-fold increased risk of venous thrombosis (OR 21.8, 95% CI 10.2 to 46.7). For immobilization alone the OR was 4.3 (95% CI 3.2 to 5.8) and immobilization with hypofibrinolysis increased the risk 10.3-fold (95% CI 7.7 to 13.8). Factor V Leiden alone increased the risk 3.5-fold (95% CI 2.3 to 5.5), and hypofibrinolysis in factor V Leiden carriers gave an OR of 8.1 (95% CI 5.3 to 12.3). The combination of hypofibrinolysis and the prothrombin 20210A mutation did not synergistically increase the risk. All ORs and 95% CIs presented are relative to individuals with CLT in the first quartile and without the other risk factor of interest.

Conclusions
The combination of hypofibrinolysis with oral contraceptive use, immobilization, or factor V Leiden results in a risk of venous thrombosis that exceeds the sum of the individual risks.

Item Type:Article
Link to this item:http://purl.utwente.nl/publications/76893
Official URL:http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.0050097
Publisher URL:http://www.plosmedicine.org/home.action
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